The influence of implant design on periprosthetic bone remodelling of two types of uncemented HA-coated hip stems. A two-year follow-up study using DEXA.

PubMed

Van der Wal, B C H; Rahmy, A I A; Grimm, B; Blake, G M; Heyligers, I C; Tonino, A J

2006-01-01

Proximal bone resorption and an increased fracture rate in the ABG-I stem has been shown. For these reasons the ABG-I stem design was changed to the ABG-II. In this study periprosthetic bone loss around the ABG-I vs ABG-II is compared to verify if the design changes resulted in improved proximal bone preservation. 51 patients were randomised to either the ABG-I or ABG-II hip prosthesis. Periprosthetic BMD change at various time points was measured using DEXA. Between the two groups (age, gender, weight etc.) no statistical difference was encountered. Compared to the baseline at two years the ABG-II preserved bone better proximally (e.g. zone 7: ABG-II: -3.7%, ABG-I: -11.9%, p=0.05) than the ABG-I. Distally, the trend was opposite and less bone loss was measured for the ABG-I than the ABG-II in zones 3, 4 and 5 (n.s.). this study confirms the philosophy behind the design changes from the ABG-I to ABG-II stem where increased elasticity, more proximal HA-coating, a shorter and distally polished stem, were meant to reduce proximal bone resorption. In future this may lead to fewer periprosthetic fractures and to less complicated revision surgery.

Class I and class II major histocompatibility molecules play a role in bone marrow-derived macrophage development

NASA Technical Reports Server (NTRS)

Armstrong, J. W.; Simske, S. J.; Beharka, A. A.; Balch, S.; Luttges, M. W.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

1994-01-01

Class I and class II major histocompatibility complex (MHC) molecules play significant roles in T cell development and immune function. We show that MHCI- and MHCII-deficient mice have low numbers of macrophage precursors and circulating monocytes, as well as abnormal bone marrow cell colony-stimulating factor type 1 secretion and bone composition. We suggest that MHCI and MHCII molecules play a significant role in macrophage development.

A paradoxical presentation of rickets and secondary osteomyelitis of the jaw in Type II autosomal dominant osteopetrosis: Rare case reports.

PubMed

Jayachandran, S; Kumar, M Suresh

2016-01-01

Osteopetrosis is a rare genetic bone disorder arising due to a defect in the differentiation or function of osteoclast which results in a generalized increase in bone mass. Osteomyelitis is one of the most common complications because of decreased bone marrow function and compromised blood supply. Radiologist plays a vital role in diagnosing osteopetrosis. Here, we present two cases of autosomal dominant osteopetrosis Type II (ADO II) with secondary osteomyelitis changes which were reported to our department. One of these two cases presented with secondary osteomyelitis in both maxilla and mandible and features of rickets, which is very rarely seen in ADO II. To the best of our knowledge, the presentation of rickets with ADO is the first of its kind to be reported. In this paper, we describe the clinical and radiological features leading to the diagnosis of ADO in these two patients. Further, a review of the literature regarding ADO is discussed.

INVESTIGATION OF BONE MINERALIZATION IN PATIENTS WITH CORONARY HEART DISEASE COMPLICATED BY CHRONIC HEART FAILURE, STAGE II-A.

PubMed

Krynytska, I; Marushchak, M; Zaets, T; Savchenko, I; Habor, H

2017-06-01

The majority of the studies have shown that individuals with cardiovascular diseases have a higher risk of experiencing bone loss and thus greater predisposition to risk of fracture. On the other hand there is growing evidence that individuals with low bone mass have higher mortality for cardiovascular events compared to patients with cardiovascular disease with normal bone mass. This research aims to investigate bone mineralization in patients with coronary heart disease complicated by stage II-A chronic heart failure. The study involved 33 men with coronary heart disease complicated by Stage II-A chronic heart failure. Bone mineral density was measured using dual energy x-ray densitometry of lumbar region of spine. Structural and functional changes of bone tissue of the lumbar spine have been found in 49,2% patients with coronary heart disease complicated by Stage II-A chronic heart failure, in particular, I stage of osteopenia - in 44,6%, II stage of osteopenia - in 27,7%, III stage of osteopenia - in 10,8% and osteoporosis - in 16,9%. It was established the same type of downward trend for BMD decreasing in L1 of patients with different stages of osteopenia, but in case of osteoporosis mineralization decreased equally in all vertebrae.

Highly efficient nuclear DNA typing of the World War II skeletal remains using three new autosomal short tandem repeat amplification kits with the extended European Standard Set of loci

PubMed Central

Zupanič Pajnič, Irena; Gornjak Pogorelc, Barbara; Balažic, Jože; Zupanc, Tomaž; Štefanič, Borut

2012-01-01

Aim To perform an efficiency study of three new amplification kits with the extended European Standard Set (ESS) of loci for autosomal short tandem repeat (STR) typing of skeletal remains excavated from the World War II mass graves in Slovenia. Methods In the beginning of the 2011, we analyzed 102 bones and teeth using the PowerPlex ESX 17 System (Promega), AmpFiSTR NGM PCR Amplification Kit (Applied Biosystems), and Investigator ESSplex Kit (Qiagen). We cleaned the bones and teeth, removed surface contamination, and ground them into a powder using liquid nitrogen. Prior to DNA isolation with Biorobot EZ1 (Qiagen), 0.5 g bone or tooth powder was decalcified. Nuclear DNA of the samples was quantified using real-time polymerase chain reaction. All three kits used the same extract with the amplification conditions recommended by the manufacturers. Results We extracted up to 131 ng DNA/g of powder from the bones and teeth. All three amplification kits showed very similar efficiency, since DNA typing was successful with all amplification kits in 101 out of 102 bones and teeth, which represents a 99% success rate. Conclusion The commercially available ESX 17, ESSplex, and NGM kits are highly reliable for STR typing of World War II skeletal remains with the DNA extraction method optimized in our laboratory. PMID:22351574

Conditional expression of constitutively active estrogen receptor {alpha} in chondrocytes impairs longitudinal bone growth in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ikeda, Kazuhiro; Tsukui, Tohru; Imazawa, Yukiko

2012-09-07

Highlights: Black-Right-Pointing-Pointer Conditional transgenic mice expressing constitutively active estrogen receptor {alpha} (caER{alpha}) in chondrocytes were developed. Black-Right-Pointing-Pointer Expression of caER{alpha} in chondrocytes impaired longitudinal bone growth in mice. Black-Right-Pointing-Pointer caER{alpha} affects chondrocyte proliferation and differentiation. Black-Right-Pointing-Pointer This mouse model is useful for understanding the physiological role of ER{alpha}in vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER{alpha}{sup ColII}, expressing constitutively activemore » mutant estrogen receptor (ER) {alpha} in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER{alpha}{sup ColII} mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER{alpha}{sup ColII} mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER{alpha}{sup ColII} mice. These results suggest that ER{alpha} is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.« less

Reconstruction with 3D-printed pelvic endoprostheses after resection of a pelvic tumour.

PubMed

Liang, H; Ji, T; Zhang, Y; Wang, Y; Guo, W

2017-02-01

The aims of this retrospective study were to report the feasibility of using 3D-printing technology for patients with a pelvic tumour who underwent reconstruction. A total of 35 patients underwent resection of a pelvic tumour and reconstruction using 3D-printed endoprostheses between September 2013 and December 2015. According to Enneking's classification of bone defects, there were three Type I lesions, 12 Type II+III lesions, five Type I+II lesions, two Type I+II+III lesions, ten type I+II+IV lesions and three type I+II+III+IV lesions. A total of three patients underwent reconstruction using an iliac prosthesis, 12 using a standard hemipelvic prosthesis and 20 using a screw-rod connected hemipelvic prosthesis. All patients had an en bloc resection. Margins were wide in 15 patients, marginal in 14 and intralesional in six. After a mean follow-up of 20.5 months (6 to 30), 25 patients survived without evidence of disease, five were alive with disease and five had died from metastatic disease. Complications included seven patients with delayed wound healing and two with a dislocation of the hip. None had a deep infection. For the 30 surviving patients, the mean Musculoskeletal Society 93 score was 22.7 (20 to 25) for patients with an iliac prosthesis, 19.8 (15 to 26) for those with a standard prosthesis, and 17.7 (9 to 25) for those with a screw-rod connected prosthesis. The application of 3D-printing technology can facilitate the precise matching and osseointegration between implants and the host bone. We found that the use of 3D-printed pelvic prostheses for reconstruction of the bony defect after resection of a pelvic tumour was safe, without additional complications, and gave good short-term functional results. Cite this article: Bone Joint J 2017;99-B:267-75. ©2017 The British Editorial Society of Bone & Joint Surgery.

A variant microcephalic osteodysplastic slender-bone disorder with growth hormone deficiency and a pigmentary retinopathy.

PubMed

Maclean, K; Ambler, G; Flaherty, M; Kozlowski, K; Adès, L C

2002-10-01

We present the case of a 3-year-old boy with post-natal growth failure, microcephaly, developmental delay, facial dysmorphism, an evolving pigmentary retinopathy, pituitary hypoplasia, micropenis, and growth hormone (GH) deficiency. He has a microcephalic osteodysplastic slender-bone disorder with disharmonic delayed osseous maturation, most closely resembling patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II). Intrauterine growth retardation, a universal finding in the MOPD II, was absent in our patient.

21 CFR 874.3300 - Hearing Aid.

Code of Federal Regulations, 2010 CFR

2010-04-01

... generic type of device includes the air-conduction hearing aid and the bone-conduction hearing aid, but... subpart E of part 807 of this chapter subject to § 874.9. (2) Class II for the bone-conduction hearing aid...

21 CFR 874.3300 - Hearing Aid.

Code of Federal Regulations, 2012 CFR

2012-04-01

... generic type of device includes the air-conduction hearing aid and the bone-conduction hearing aid, but... subpart E of part 807 of this chapter subject to § 874.9. (2) Class II for the bone-conduction hearing aid...

21 CFR 874.3300 - Hearing Aid.

Code of Federal Regulations, 2014 CFR

2014-04-01

... generic type of device includes the air-conduction hearing aid and the bone-conduction hearing aid, but... subpart E of part 807 of this chapter subject to § 874.9. (2) Class II for the bone-conduction hearing aid...

21 CFR 874.3300 - Hearing Aid.

Code of Federal Regulations, 2013 CFR

2013-04-01

... generic type of device includes the air-conduction hearing aid and the bone-conduction hearing aid, but... subpart E of part 807 of this chapter subject to § 874.9. (2) Class II for the bone-conduction hearing aid...

21 CFR 874.3300 - Hearing Aid.

Code of Federal Regulations, 2011 CFR

2011-04-01

... generic type of device includes the air-conduction hearing aid and the bone-conduction hearing aid, but... subpart E of part 807 of this chapter subject to § 874.9. (2) Class II for the bone-conduction hearing aid...

Inhibitory effect of auranofin (I) and chloroquine (II) on bone degradation induced by the interleukin 1-like (IL-1-like) factor released from rheumatoid synovial tissue (RAST) in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodges, Y.; Maser, M.R.; Britton, M.C.

1986-03-01

RAST, maintained in organ culture, releases two distinct types of bone resorptive factors and one co-resorptive factor. The first is prostaglandin E/sub 2/ (PGE/sub 2/), while the second is a protein with properties of IL-1. The co-resorptive factor collagenase, cannot induce bone resorption by itself, but augments the bone resorptive activity initiated by either PGE/sub 2/ or the IL-l-like factor. Bone resorptive activity was assessed by measuring the release of /sup 45/Ca from prelabelled rat fetal bones. We investigated the effects of five non-steroidal anti-inflammatory drugs (NSAIDs) and two disease-modifying anti-rheumatic drugs (DMARDs), (I) and (II), on bone degradation mediatedmore » by the IL-l-like factor. None of the NSAIDs tested inhibited bone degradation at 5 x 10/sup -5/ M. On the other hand, both (I) and (II) inhibited bone degradation 60 to 100% at 1 x 10/sup -6/ M and 8 x 10/sup -6/ M respectively. They can inhibit the action of IL-l-like factor on bone at therapeutically attainable concentrations. Additionally, both (I) and (II) block the release of collagenase from the organ culture of RAST with IC/sub 50/s of 5 x 10/sup -6/ M. This unique ability to inhibit collagenase release may contribute to their effectiveness is preventing bone loss in this test model.« less

Transient chondrogenic phase in the intramembranous pathway during normal skeletal development.

PubMed

Nah, H D; Pacifici, M; Gerstenfeld, L C; Adams, S L; Kirsch, T

2000-03-01

Calvarial and facial bones form by intramembranous ossification, in which bone cells arise directly from mesenchyme without an intermediate cartilage anlage. However, a number of studies have reported the emergence of chondrocytes from in vitro calvarial cell or organ cultures and the expression of type II collagen, a cartilage-characteristic marker, in developing calvarial bones. Based on these findings we hypothesized that a covert chondrogenic phase may be an integral part of the normal intramembranous pathway. To test this hypothesis, we analyzed the temporal and spatial expression patterns of cartilage characteristic genes in normal membranous bones from chick embryos at various developmental stages (days 12, 15 and 19). Northern and RNAse protection analyses revealed that embryonic frontal bones expressed not only the type I collagen gene but also a subset of cartilage characteristic genes, types IIA and XI collagen and aggrecan, thus resembling a phenotype of prechondrogenic-condensing mesenchyme. The expression of cartilage-characteristic genes decreased with the progression of bone maturation. Immunohistochemical analyses of developing embryonic chick heads indicated that type II collagen and aggrecan were produced by alkaline phosphatase activity positive cells engaged in early stages of osteogenic differentiation, such as cells in preosteogenic-condensing mesenchyme, the cambium layer of periosteum, the advancing osteogenic front, and osteoid bone. Type IIB and X collagen messenger RNAs (mRNA), markers for mature chondrocytes, were also detected at low levels in calvarial bone but not until late embryonic stages (day 19), indicating that some calvarial cells may undergo overt chondrogenesis. On the basis of our findings, we propose that the normal intramembranous pathway in chicks includes a previously unrecognized transient chondrogenic phase similar to prechondrogenic mesenchyme, and that the cells in this phase retain chondrogenic potential that can be expressed in specific in vitro and in vivo microenvironments.

The influence of micro and macro-geometry in term of bone-implant interface in two implant systems: an histomorphometrical study

PubMed Central

ROCCI, A.; CALCATERRA, R.; DI GIROLAMO, M.; ROCCI, M.; ROCCI, C.; BAGGI, L.

2015-01-01

SUMMARY Objective Many factors could affect the osseous healing of implants such as surface topography of biomaterial, the status of the bone/implant site, implant loading conditions, surgical technique and implant design. The aim of this study was to analyze the BIC of 2 different implants systems characterized by different micro and macrogeometry, that were placed in the posterior maxillary and mandibular jaws of humans, clinically unloaded and retrieved for histomorphometric analyses after 12 weeks. Material and method The patients were divided in two groups (Group I and II); group I was composed by 4 patients that each received in the posterior areas of mandible one type A implant [GTB-Plan1Health Amaro (UD) Italy] one type B implant (OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). Group II was composed by 3 patients that each received in the posterior areas of jawsbone one type A implant [GTB-Plan1Health Amaro (UD) Italy] one type B implant (OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). After 12 weeks of healing all the implants of both groups were harvested with the peri-implant bone tissues. Osseointegration process was evaluated throughout measurements of BIC. Results No statistical significance differences were found among the mean percentage of BIC of Group I – type A were 66,51% versus 49,96% in Group I – type B, as well as among the mean percentage of BIC of Group II – type A were 43.7% versus 60.02% in Group II – type B. Conclusions Our results highlight that the mean percentage of BIC after 12 weeks from the implants placement without functional loading is not influenced by the composition of the implant surface. PMID:28042421

The influence of micro and macro-geometry in term of bone-implant interface in two implant systems: an histomorphometrical study.

PubMed

Rocci, A; Calcaterra, R; DI Girolamo, M; Rocci, M; Rocci, C; Baggi, L

2015-01-01

Many factors could affect the osseous healing of implants such as surface topography of biomaterial, the status of the bone/implant site, implant loading conditions, surgical technique and implant design. The aim of this study was to analyze the BIC of 2 different implants systems characterized by different micro and macrogeometry, that were placed in the posterior maxillary and mandibular jaws of humans, clinically unloaded and retrieved for histomorphometric analyses after 12 weeks. The patients were divided in two groups (Group I and II); group I was composed by 4 patients that each received in the posterior areas of mandible one type A implant [GTB-Plan1Health Amaro (UD) Italy] one type B implant (OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). Group II was composed by 3 patients that each received in the posterior areas of jawsbone one type A implant [GTB-Plan1Health Amaro (UD) Italy] one type B implant (OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). After 12 weeks of healing all the implants of both groups were harvested with the peri-implant bone tissues. Osseointegration process was evaluated throughout measurements of BIC. No statistical significance differences were found among the mean percentage of BIC of Group I - type A were 66,51% versus 49,96% in Group I - type B, as well as among the mean percentage of BIC of Group II - type A were 43.7% versus 60.02% in Group II - type B. Our results highlight that the mean percentage of BIC after 12 weeks from the implants placement without functional loading is not influenced by the composition of the implant surface.

The Comparative Efficiency of Four Types of Endodontic Files and Reamers.

DTIC Science & Technology

1981-12-29

an reveree aide Ii neceeary end Identify by block number) Comparative efficiency of endodontic files; endodontic instrumentation ; instrumentation ...sections of bovine bone. Each canal was instrumented to a size 80 using four types of endodontic instruments : Hedstrom S files; K-files; reamers; and the...bovine bone. Each canal was instrumented to a size 80 using four types of endodontic instruments : Hedstrom files; K-files; reamers; and the new Unifile

[Polarized microscopic observation of the collagen change in bone healing during bone lengthening].

PubMed

Zou, Pei; Li, Junhui; Li, Zhuyi

2006-01-01

To investigate the feature and regularity of the collagen change in bone healing during bone lengthening. Bone lengthening model was made in the middle segment of the rabbit tibia. Five days after the model was established, the bone was lengthened 1.5 mm per day for 14 days. The rabbits were put to death after elongation, 7, 14, 21, 30, 40, 50, 60 and 70 days after elongation. The distracted area of the bone was imbedded with paraffin. After being stained by the picric acid-sirius red staining, the slice was observed under polarized microscope. The features of the collagen change in the distracted bone were as follows: (1) In the fibrous tissue of the distracted area during lengthening period and the early stage after lengthening, there was not only collagen III but also much collagen I. (2) Collagen I , II and III were observed in the cartilage. (3) Collagen I, II and III were also observed in the pseudo-growth plate. (4) Collagen I took the dominance during lengthening period and the late stage after lengthening. New bone formation in bone lengthening is under the distracted force, so the collagen changes have different features compared with that in fracture healing. Collagen I, II and III can be identified by picric acid-sirius red staining and polarized microscope, so a new method for studying the collagen typing in bone repairing is provided.

ACTN3 R577X Genotypes Associate with Class II and Deep Bite Malocclusions

PubMed Central

Zebrick, Brian; Teeramongkolgul, Teesit; Nicot, Romain; Horton, Michael J.; Raoul, Gwenael; Ferri, Joel; Vieira, Alexandre R.; Sciote, James J.

2014-01-01

Introduction α-actinins are myofibril anchor proteins which influence contractile properties of skeletal muscle. ACTN2 is expressed in slow type I and fast type II fibers whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (i.e. changing 577RR to 577XX - the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminished fast contractile ability, enhanced endurance performance and reduced bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in masseter muscle of orthognathic surgery patients to determine genotype associations with malocclusion. Methods Clinical information, masseter muscle biopsies and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 SNPs, RT-PCR quantitation of muscle gene message and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. Results Muscle mRNA expression level was significantly different for ACTN3 SNP genotypes (p<0.01). The frequency of ACTN3 genotypes was significantly different for sagittal and vertical classifications of malocclusion with the clearest association being elevated 577XX genotype in skeletal class II malocclusion (p = 0.003). This genotype also resulted in significantly smaller diameter of fast type II fibers in masseter muscle (p = 0.002). Conclusion ACTN3 577XX is overrepresented in skeletal class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in deep bite malocclusion, suggesting muscle differences contribute to variations in vertical facial dimensions. PMID:25439211

Telomerase deficiency in bone marrow-derived cells attenuates angiotensin II-induced abdominal aortic aneurysm formation.

PubMed

Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Cohn, Dianne; Heywood, Elizabeth B; Jones, Karrie L; Lovett, David H; Howatt, Deborah A; Daugherty, Alan; Bruemmer, Dennis

2011-02-01

Abdominal aortic aneurysms (AAA) are an age-related vascular disease and an important cause of morbidity and mortality. In this study, we sought to determine whether the catalytic component of telomerase, telomerase reverse transcriptase (TERT), modulates angiotensin (Ang) II-induced AAA formation. Low-density lipoprotein receptor-deficient (LDLr-/-) mice were lethally irradiated and reconstituted with bone marrow-derived cells from TERT-deficient (TERT-/-) mice or littermate wild-type mice. Mice were placed on a diet enriched in cholesterol, and AAA formation was quantified after 4 weeks of Ang II infusion. Repopulation of LDLr-/- mice with TERT-/- bone marrow-derived cells attenuated Ang II-induced AAA formation. TERT-deficient recipient mice revealed modest telomere attrition in circulating leukocytes at the study end point without any overt effect of the donor genotype on white blood cell counts. In mice repopulated with TERT-/- bone marrow, aortic matrix metalloproteinase-2 (MMP-2) activity was reduced, and TERT-/- macrophages exhibited decreased expression and activity of MMP-2 in response to stimulation with Ang II. Finally, we demonstrated in transient transfection studies that TERT overexpression activates the MMP-2 promoter in macrophages. TERT deficiency in bone marrow-derived macrophages attenuates Ang II-induced AAA formation in LDLr-/- mice and decreases MMP-2 expression. These results point to a previously unrecognized role of TERT in the pathogenesis of AAA.

Suture anchor fixation strength with or without augmentation in osteopenic and severely osteoporotic bones in rotator cuff repair: a biomechanical study on polyurethane foam model.

PubMed

Er, Mehmet Serhan; Altinel, Levent; Eroglu, Mehmet; Verim, Ozgur; Demir, Teyfik; Atmaca, Halil

2014-08-22

The purpose of the present study was to compare the results of various types of anchor applications with or without augmentation in both osteopenic and severely osteoporotic bone models. Two different types of suture anchors were tested in severely osteoporotic (SOP) and osteopenic polyurethane (PU) foam blocks using an established protocol. An Instron machine applied static loading parallel to the axis of insertion until failure, and the mean anchor failure strengths were calculated. The mode of failure (anchor pullout, suture tear) was recorded. The anchors tested included the Corkscrew (CS) (Arthrex Inc., Naples, FL, USA) (without augmentation, polymethylmethacrylate (PMMA)-augmented, and bioabsorbable tricalcium phosphate (TCP) cement-augmented) and Corkscrew FT II (CS FT II) 5.5 mm (without augmentation as used routinely). The mean failure loads for both SOP and osteopenic PU foam blocks, respectively, were as follows: CS, 16.2 and 212.4 N; CS with TCP, 75.2 and 396 N; CS with PMMA, 101.2 and 528.8 N; CS FT II, 13.8 and 339.8 N. Augmentation of CS with TCP or PMMA would be essential to SOP bones. In the osteopenic bone model, although anchor fixation augmented with PMMA is the best fixation method, CS augmented with TCP cement or CS FT II without any need for augmentation may also be used as an alternative.

Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice.

PubMed

Zhang, Y; Wang, L; Song, Y; Zhao, X; Wong, M S; Zhang, W

2016-03-01

The skeletal renin-angiotensin system contributes to the development of osteoporosis. The renin inhibitor aliskiren exhibited beneficial effects on trabecular bone of osteoporotic mice, and this action might be mediated through angiotensin and bradykinin receptor pathways. This study implies the potential application of renin inhibitor in the management for postmenopausal osteoporosis. The skeletal renin-angiotensin system plays key role in the pathological process of osteoporosis. The present study is designed to elucidate the effect of renin inhibitor aliskiren on trabecular bone and its potential action mechanism in ovariectomized (OVX) mice. The OVX mice were treated with low dose (5 mg/kg) or high dose (25 mg/kg) of aliskiren or its vehicle for 8 weeks. The bone turnover markers were measured by ELISA. The structural parameters of trabecular bone at lumbar vertebra (LV) and distal femoral metaphysis were measured by micro-CT. The expression of messenger RNA (mRNA) and protein was studied by RT-PCR and immunoblotting, respectively. Aliskiren treatment reduced urinary excretion of calcium and serum level of tartrate-resistant acid phosphatase in OVX mice. The treatment with aliskiren significantly increased bone volume (BV/TV) and connectivity density (Conn.D) of trabecular bone at LV-2 and LV-5 as well as dramatically enhanced BV/TV, Conn.D, bone mineral density (BMD/BV) and decreased bone surface (BS/BV) at the distal femoral end. Aliskiren significantly down-regulated the expression of angiotensinogen, angiotensin II (Ang II), Ang II type 1 receptor, bradykinin receptor (BR)-1, and osteocytic-specific gene sclerostin as well as the osteoclast-specific genes, including carbonic anhydrase II, matrix metalloproteinase-9, and cathepsin K. This study revealed that renin inhibitor aliskiren exhibited the beneficial effects on trabecular bone of ovariectomy-induced osteoporotic mice, and the underlying mechanism for this action might be mediated through Ang II and BR signaling pathways in bone.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Culbert, A.A.; Wallis, G.A.; Kadler, K.E.

The brittleness of bone in people with lethal (type II) osteogenesis imperfecta, a heritable disorder caused by mutations in the type I collagen genes, arises from the deposition of abnormal collagen in the bone matrix. The inability of the abnormal collagen to participate in mineralization may be caused by its failure to interact with other bone proteins. Here, we have designed a strategy to isolate the genes important for mineralization of collagen during bone formation. Cells isolated from 16-day embryonic chick calvaria and seeded post-confluence in culture deposited a mineralized matrix over a period of 2 weeks. Chick skin fibroblastsmore » seeded and cultured under the same conditions did not mineralize. Using RT-PCR, we prepared short cDNAs ({approximately}300 bp) corresponding to the 3{prime} ends of mRNA from fibroblasts and separately from the mineralizing calvarial cells. Subtractive cDNA hybridization generated a pool of cDNAs that were specific to mineralizing calvarial cells but not to fibroblasts. Screening of 100,000 plaques of a chick bone ZAP Express cDNA library with this pool of mineralizing-specific cDNAs identified ten clones which comprised full-length cDNAs for the bone proteins osteopontin (eight of the ten positives), bone sialoprotein II (one of the ten positives), and cystatin (one of the ten positives). cDNAs for type I collagen, fibronectin, alkaline phosphatase, house-keeping genes, and other genes expressed in fibroblasts were not identified in this preliminary screen. The pool of short cDNAs is likely to comprise cDNAs for further bone-specific genes and will be used to screen the entire bone cDNA library of 4.2 million clones. 30 refs., 4 figs.« less

Management of Type II Odontoid Fracture for Osteoporotic Bone Structure: Preliminary Report.

PubMed

Cosar, Murat; Ozer, A Fahir; Alkan, Bahadır; Guven, Mustafa; Akman, Tarık; Aras, Adem Bozkurt; Ceylan, Davut; Tokmak, Mehmet

2015-01-01

Anterior transodontoid screw fixation technique is generally chosen for the management of type II odontoid fractures. The nonunion of type II odontoid fractures is still a major problem especially in elderly and osteoporotic patients. Eleven osteoporotic type II odontoid fracured patients were presented in this article. We have divided 11 patients in two groups as classical and Ozer's technique. We have also compared (radiologically and clinically) the classical anterior transodontoid screw fixation (group II: 6 cases) and Ozer's transodontoid screw fixation technique (group I: 5 cases) retrospectively. There was no difference regaring the clinical features of the groups. However, the radiological results showed 100% fusion for Ozer's screw fixation technique and 83% fusion for the classical screw fixation technique. In conclusion, we suggest that Ozer's technique may help to increase the fusion capacity for osteoporotic type II odontoid fractures.

Suture anchor fixation strength with or without augmentation in osteopenic and severely osteoporotic bones in rotator cuff repair: a biomechanical study on polyurethane foam model

PubMed Central

2014-01-01

Background The purpose of the present study was to compare the results of various types of anchor applications with or without augmentation in both osteopenic and severely osteoporotic bone models. Methods Two different types of suture anchors were tested in severely osteoporotic (SOP) and osteopenic polyurethane (PU) foam blocks using an established protocol. An Instron machine applied static loading parallel to the axis of insertion until failure, and the mean anchor failure strengths were calculated. The mode of failure (anchor pullout, suture tear) was recorded. The anchors tested included the Corkscrew® (CS) (Arthrex Inc., Naples, FL, USA) (without augmentation, polymethylmethacrylate (PMMA)-augmented, and bioabsorbable tricalcium phosphate (TCP) cement-augmented) and Corkscrew® FT II (CS FT II) 5.5 mm (without augmentation as used routinely). Results The mean failure loads for both SOP and osteopenic PU foam blocks, respectively, were as follows: CS, 16.2 and 212.4 N; CS with TCP, 75.2 and 396 N; CS with PMMA, 101.2 and 528.8 N; CS FT II, 13.8 and 339.8 N. Conclusions Augmentation of CS with TCP or PMMA would be essential to SOP bones. In the osteopenic bone model, although anchor fixation augmented with PMMA is the best fixation method, CS augmented with TCP cement or CS FT II without any need for augmentation may also be used as an alternative. PMID:25148925

Does microvascularization of the footprint play a role in rotator cuff healing of the shoulder?

PubMed

Bonnevialle, Nicolas; Bayle, Xavier; Faruch, Marie; Wargny, Matthieu; Gomez-Brouchet, Anne; Mansat, Pierre

2015-08-01

The aim of the study was to evaluate the relationship between bone microvascularization of the footprint and tendon integrity after rotator cuff repair of the shoulder. Forty-eight patients (mean age, 59 years; ±7.9) with a chronic rotator cuff tear underwent a tendon repair with a single-row technique and were studied prospectively. A core obtained from the footprint during the procedure allowed determination of the bone's microvascularization with an immunohistochemistry technique using anti-CD34 antibodies. Clinical evaluation was performed at a minimum of 12-month follow-up, and rotator cuff integrity was assessed with ultrasound according to Sugaya's classification. At a mean follow-up of 13 months, the Constant score improved from 40 to 75 points; American Shoulder and Elbow Surgeons score, from 59 to 89 points; and subjective shoulder value, from 38% to 83% (P < .001). Ultrasound identified 18 patients with Sugaya type I healing, 27 patients with type II, and 3 patients with type IV. No patients showed Sugaya type III or V repairs. The rate of microvascularization of the footprint was 15.6%, 13.9%, and 4.2% for type I, II, and IV tendon integrity, respectively (I vs. II, P = .22; II vs. IV, P = .02; I vs. IV, P = .0022). Patients with a history of corticosteroid injection had a lower rate of microvascularization than the others (10.3% vs. 16.2%; P = .03). Even if overall satisfactory clinical outcomes are achieved after a rotator cuff repair, bone microvascularization of the footprint plays a role in rotator cuff healing. A lower rate of microvessels decreases the tendon integrity and healing potential after repair. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

[Diagnostic values of serum type III procollagen N-terminal peptide in type IV gastric cancer].

PubMed

Akazawa, S; Fujiki, T; Kanda, Y; Kumai, R; Yoshida, S

1985-04-01

Since increased synthesis of collagen has been demonstrated in tissue of type IV gastric cancer, we attempted to distinguish type IV gastric cancer from other cancers by measuring serum levels of type III procollagen N-terminal peptide (type III-N-peptide). Mean serum levels in type IV gastric cancer patients without metastasis were found to be elevated above normal values and developed a tendency to be higher than those in types I, II and III gastric cancer patients without metastasis. Highly positive ratios were found in patients with liver diseases including hepatoma and colon cancer, biliary tract cancer, and esophageal cancer patients with liver, lung or bone metastasis, but only 2 out of 14 of these cancer patients without such metastasis showed positive serum levels of type III-N-peptide. Positive cases in patients with type IV gastric cancer were obtained not only in the group with clinical stage IV but also in the groups with clinical stages II and III. In addition, high serum levels of type III-N-peptide in patients with type IV gastric cancer were seen not only in the cases with liver, lung or bone metastasis but also in cases with disseminated peritoneal metastasis alone. These results suggest that if the serum level of type III-N-peptide is elevated above normal values, type IV gastric cancer should be suspected after ruling out liver diseases, myelofibrosis and liver, lung or bone metastasis.

Glycation Contributes to Interaction Between Human Bone Alkaline Phosphatase and Collagen Type I.

PubMed

Halling Linder, Cecilia; Enander, Karin; Magnusson, Per

2016-03-01

Bone is a biological composite material comprised primarily of collagen type I and mineral crystals of calcium and phosphate in the form of hydroxyapatite (HA), which together provide its mechanical properties. Bone alkaline phosphatase (ALP), produced by osteoblasts, plays a pivotal role in the mineralization process. Affinity contacts between collagen, mainly type II, and the crown domain of various ALP isozymes were reported in a few in vitro studies in the 1980s and 1990s, but have not attracted much attention since, although such interactions may have important implications for the bone mineralization process. The objective of this study was to investigate the binding properties of human collagen type I to human bone ALP, including the two bone ALP isoforms B1 and B2. ALP from human liver, human placenta and E. coli were also studied. A surface plasmon resonance-based analysis, supported by electrophoresis and blotting, showed that bone ALP binds stronger to collagen type I in comparison with ALPs expressed in non-mineralizing tissues. Further, the B2 isoform binds significantly stronger to collagen type I in comparison with the B1 isoform. Human bone and liver ALP (with identical amino acid composition) displayed pronounced differences in binding, revealing that post-translational glycosylation properties govern these interactions to a large extent. In conclusion, this study presents the first evidence that glycosylation differences in human ALPs are of crucial importance for protein-protein interactions with collagen type I, although the presence of the ALP crown domain may also be necessary. Different binding affinities among the bone ALP isoforms may influence the mineral-collagen interface, mineralization kinetics, and degree of bone matrix mineralization, which are important factors determining the material properties of bone.

Resistance Training in Type II Diabetes Mellitus: Impact on Areas of Metabolic Dysfunction in Skeletal Muscle and Potential Impact on Bone

PubMed Central

Wood, Richard J.; O'Neill, Elizabeth C.

2012-01-01

The prevalence of Type II Diabetes mellitus (T2DM) is increasing rapidly and will continue to be a major healthcare expenditure burden. As such, identification of effective lifestyle treatments is paramount. Skeletal muscle and bone display metabolic and functional disruption in T2DM. Skeletal muscle in T2DM is characterized by insulin resistance, impaired glycogen synthesis, impairments in mitochondria, and lipid accumulation. Bone quality in T2DM is decreased, potentially due to the effects of advanced glycation endproducts on collagen, impaired osteoblast activity, and lipid accumulation. Although exercise is widely recognized as an important component of treatment for T2DM, the focus has largely been on aerobic exercise. Emerging research suggests that resistance training (strength training) may impose potent and unique benefits in T2DM. The purpose of this review is to examine the role of resistance training in treating the dysfunction in skeletal muscle and the potential role for resistance training in treating the associated dysfunction in bone. PMID:22474580

Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA).

PubMed

Bagi, C M; Berryman, E R; Teo, S; Lane, N E

2017-12-01

The aim of this study was to determine the ability of undenatured native chicken type II collagen (UC-II) to prevent excessive articular cartilage deterioration in a rat model of osteoarthritis (OA). Twenty male rats were subjected to partial medial meniscectomy tear (PMMT) surgery to induce OA. Immediately after the surgery 10 rats received vehicle and another 10 rats oral daily dose of UC-II at 0.66 mg/kg for a period of 8 weeks. In addition 10 naïve rats were used as an intact control and another 10 rats received sham surgery. Study endpoints included a weight-bearing capacity of front and hind legs, serum biomarkers of bone and cartilage metabolism, analyses of subchondral and cancellous bone at the tibial epiphysis and metaphysis, and cartilage pathology at the medial tibial plateau using histological methods. PMMT surgery produced moderate OA at the medial tibial plateau. Specifically, the deterioration of articular cartilage negatively impacted the weight bearing capacity of the operated limb. Immediate treatment with the UC-II preserved the weight-bearing capacity of the injured leg, preserved integrity of the cancellous bone at tibial metaphysis and limited the excessive osteophyte formation and deterioration of articular cartilage. Study results demonstrate that a clinically relevant daily dose of UC-II when applied immediately after injury can improve the mechanical function of the injured knee and prevent excessive deterioration of articular cartilage. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Decreased bone formation and increased osteoclastogenesis cause bone loss in mucolipidosis II

PubMed Central

Kollmann, Katrin; Pestka, Jan Malte; Kühn, Sonja Christin; Schöne, Elisabeth; Schweizer, Michaela; Karkmann, Kathrin; Otomo, Takanobu; Catala-Lehnen, Philip; Failla, Antonio Virgilio; Marshall, Robert Percy; Krause, Matthias; Santer, Rene; Amling, Michael; Braulke, Thomas; Schinke, Thorsten

2013-01-01

Mucolipidosis type II (MLII) is a severe multi-systemic genetic disorder caused by missorting of lysosomal proteins and the subsequent lysosomal storage of undegraded macromolecules. Although affected children develop disabling skeletal abnormalities, their pathogenesis is not understood. Here we report that MLII knock-in mice, recapitulating the human storage disease, are runted with accompanying growth plate widening, low trabecular bone mass and cortical porosity. Intralysosomal deficiency of numerous acid hydrolases results in accumulation of storage material in chondrocytes and osteoblasts, and impaired bone formation. In osteoclasts, no morphological or functional abnormalities are detected whereas osteoclastogenesis is dramatically increased in MLII mice. The high number of osteoclasts in MLII is associated with enhanced osteoblastic expression of the pro-osteoclastogenic cytokine interleukin-6, and pharmacological inhibition of bone resorption prevented the osteoporotic phenotype of MLII mice. Our findings show that progressive bone loss in MLII is due to the presence of dysfunctional osteoblasts combined with excessive osteoclastogenesis. They further underscore the importance of a deep skeletal phenotyping approach for other lysosomal diseases in which bone loss is a prominent feature. PMID:24127423

Fcγ receptor-mediated influx of S100A8/A9-producing neutrophils as inducer of bone erosion during antigen-induced arthritis.

PubMed

Di Ceglie, Irene; Ascone, Giuliana; Cremers, Niels A J; Sloetjes, Annet W; Walgreen, Birgitte; Vogl, Thomas; Roth, Johannes; Verbeek, J Sjef; van de Loo, Fons A J; Koenders, Marije I; van der Kraan, Peter M; Blom, Arjen B; van den Bosch, Martijn H J; van Lent, Peter L E M

2018-05-02

Osteoclast-mediated bone erosion is a central feature of rheumatoid arthritis (RA). Immune complexes, present in a large percentage of patients, bind to Fcγ receptors (FcγRs), thereby modulating the activity of immune cells. In this study, we investigated the contribution of FcγRs, and FcγRIV in particular, during antigen-induced arthritis (AIA). AIA was induced in knee joints of wild-type (WT), FcγRI,II,III -/- , and FcγRI,II,III,IV -/- mice. Bone destruction, numbers of tartrate-resistant acid phosphatase-positive (TRAP + ) osteoclasts, and inflammation were evaluated using histology; expression of the macrophage marker F4/80, neutrophil marker NIMPR14, and alarmin S100A8 was evaluated using immunohistochemistry. The percentage of osteoclast precursors in the bone marrow was determined using flow cytometry. In vitro osteoclastogenesis was evaluated with TRAP staining, and gene expression was assessed using real-time PCR. FcγRI,II,III,IV -/- mice showed decreased bone erosion compared with WT mice during AIA, whereas both the humoral and cellular immune responses against methylated bovine serum albumin were not impaired in FcγRI,II,III,IV -/- mice. The percentage of osteoclast precursors in the bone marrow of arthritic mice and their ability to differentiate into osteoclasts in vitro were comparable between FcγRI,II,III,IV -/- and WT mice. In line with these observations, numbers of TRAP + osteoclasts on the bone surface during AIA were comparable between the two groups. Inflammation, a process that strongly activates osteoclast activity, was reduced in FcγRI,II,III,IV -/- mice, and of note, mainly decreased numbers of neutrophils were present in the joint. In contrast to FcγRI,II,III,IV -/- mice, AIA induction in knee joints of FcγRI,II,III -/- mice resulted in increased bone erosion, inflammation, and numbers of neutrophils, suggesting a crucial role for FcγRIV in the joint pathology by the recruitment of neutrophils. Finally, significant correlations were found between bone erosion and the number of neutrophils present in the joint as well as between bone erosion and the number of S100A8-positive cells, with S100A8 being an alarmin strongly produced by neutrophils that stimulates osteoclast resorbing activity. FcγRs play a crucial role in the development of bone erosion during AIA by inducing inflammation. In particular, FcγRIV mediates bone erosion in AIA by inducing the influx of S100A8/A9-producing neutrophils into the arthritic joint.

[Study on the correlation between syndrome differ classification of knee osteoarthritis and X-ray image].

PubMed

Jin, Li-Kun; Zhang, Guo-Zhong; Tang, Ke; Liu, Yang

2010-12-01

To study the correlation between syndrome differ classification of knee osteoarthritis and X-ray image, so as to provide evidence for clinical diagnosis and treatment. From Jun. 2007 to Dec. 2007, 78 patients (108 knees) with knee osteoarthritis were reviewed, including 65 females (89 knees) and 13 males (19 knees), ranging in age from 41 to 77 years. According to the standards for the differentiation of syndrome in the treatment of knee osteoarthritis defined in Principle of Clinical Research for New Traditional Herbs, the patients were divided into three types: Type I, insufficiency of the liver and kidney, with stagnation of tendons and muscles, 43 knees; Type II, insufficiency of the spleen and kidney, with dampness infusion into bone and joints, 26 knees; Type I, deficiency of the liver and kidney, with inter-obstruction of phlegm and stasis 39 knees. Normotopia and lateral plain film of knee joint of weigh loading and in erect position, and patellofemoral Skyline plain flim was taken. Joint space narrow, osteophyte generation, subchondral osteosclerosis and subchondral cystic degeneration were evaluated. All data were analyzed by K independent samples nonparametric test in order to find out the correlation between syndrome differ classification of knee osteoarthritis and X-ray image. It was shown that after K independent samples nonparametric test about syndrome differ classification of knee osteoarthritis and X-ray image: there were significant differences among three types about lateral patella osteophyte, condyles of tibia osteophyte and Type II was the most serious, Type I was secondary, Type II was the lightest. Other index had no obvious difference among the three groups. There is certain correlation between syndrome differ classification of knee osteoarthritis and X-ray image. There are significant differences among three types about lateral patella osteophyte, condyles of tibia osteophyte, the Type II is the most serious,Type I is secondary, Type II is the lightest. Consequently, it can be deduced that worse osteophyte is one of accordances of Type II-insufficiency of the spleen and kidney, with dampness infusion into bone and joints. And, the Type II is more serious stage in radiologic manifestation.

Effects of major histocompatibility complex class II knockout on mouse bone mechanical properties during development

NASA Technical Reports Server (NTRS)

Simske, Steven J.; Bateman, Ted A.; Smith, Erin E.; Ferguson, Virginia L.; Chapes, Stephen K.

2002-01-01

We investigated the effect of major histocompatibility complex class II (MHC II) knockout on the development of the mouse peripheral skeleton. These C2D mice had less skeletal development at 8, 12 and 16 weeks of age compared to wild-type C57BL/6J (B6) male mice. The C2D mice had decreased femur mechanical, geometric and compositional measurements compared to wild type mice at each of these ages. C2D femur stiffness (S), peak force in 3-pt bending (Pm), and mineral mass (Min-M) were 74%, 64% and 66%, respectively, of corresponding B6 values at 8 weeks of age. Similar differences were measured at 12 weeks (for which C2D femoral S, Pm and Min-M were 71%, 72% and 73%, respectively, of corresponding B6 values) and at 16 weeks (for which C2D femoral S, Pm and Min-M were 80%, 66% and 61%, respectively, of corresponding B6 values). MHC II knockout delays the development of adult bone properties and is accompanied by lower body mass compared to wild-type controls.

Acemannan sponges stimulate alveolar bone, cementum and periodontal ligament regeneration in a canine class II furcation defect model.

PubMed

Chantarawaratit, P; Sangvanich, P; Banlunara, W; Soontornvipart, K; Thunyakitpisal, P

2014-04-01

Periodontal disease is a common infectious disease, found worldwide, causing the destruction of the periodontium. The periodontium is a complex structure composed of both soft and hard tissues, thus an agent applied to regenerate the periodontium must be able to stimulate periodontal ligament, cementum and alveolar bone regeneration. Recent studies demonstrated that acemannan, a polysaccharide extracted from Aloe vera gel, stimulated both soft and hard tissue healing. This study investigated effect of acemannan as a bioactive molecule and scaffold for periodontal tissue regeneration. Primary human periodontal ligament cells were treated with acemannan in vitro. New DNA synthesis, expression of growth/differentiation factor 5 and runt-related transcription factor 2, expression of vascular endothelial growth factor, bone morphogenetic protein-2 and type I collagen, alkaline phosphatase activity, and mineralized nodule formation were determined using [(3)H]-thymidine incorporation, reverse transcription-polymerase chain reaction, enzyme-linked immunoabsorbent assay, biochemical assay and alizarin red staining, respectively. In our in vivo study, premolar class II furcation defects were made in four mongrel dogs. Acemannan sponges were applied into the defects. Untreated defects were used as a negative control group. The amount of new bone, cementum and periodontal ligament formation were evaluated 30 and 60 d after the operation. Acemannan significantly increased periodontal ligament cell proliferation, upregulation of growth/differentiation factor 5, runt-related transcription factor 2, vascular endothelial growth factor, bone morphogenetic protein 2, type I collagen and alkaline phosphatase activity, and mineral deposition as compared with the untreated control group in vitro. Moreover, acemannan significantly accelerated new alveolar bone, cementum and periodontal ligament formation in class II furcation defects. Our data suggest that acemannan could be a candidate biomolecule for periodontal tissue regeneration. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chronic shin splints. Classification and management of medial tibial stress syndrome.

PubMed

Detmer, D E

1986-01-01

A clinical classification and treatment programme has been developed for chronic medial tibial stress syndrome. Medial tibial stress syndrome has been reported to be either tibial stress fracture or microfracture, tibial periostitis, or distal deep posterior chronic compartment syndrome. Three chronic types exist and may coexist: Type I (tibial microfracture, bone stress reaction or cortical fracture); type II (periostalgia from chronic avulsion of the periosteum at the periosteal-fascial junction); and type III (chronic compartment syndrome syndrome). Type I disease is treated nonoperatively. Operations for resistant types II and III medial tibial stress syndrome were performed in 41 patients. Bilaterality was common (type II, 50% type III, 88%). Seven had coexistent type II/III; one had type I/II. Preoperative symptoms averaged 24 months in type II, 6 months in type III, and 33 months in types II/III. Mean age was 22 years (15 to 51). Resting compartment pressures were normal in type II (mean 12 mm Hg) and elevated in type III and type II/III (mean 23 mm Hg). Type II and type II/III patients received fasciotomy plus periosteal cauterisation. Type III patients had fasciotomy only. All procedures were performed on an outpatient basis using local anaesthesia. Follow up was complete and averaged 6 months (2 to 14 months). Improved performance was as follows: type II, 93%, type III, 100%; type II/III, 86%. Complete cures were as follows: type II, 78%; type III, 75%; and type II/III, 57%. This experience suggests that with precise diagnosis and treatment involving minimal risk and cost the athlete has a reasonable chance of return to full activity.

Effects of in vivo static compressive loading on aggrecan and type II and X collagens in the rat growth plate extracellular matrix.

PubMed

Cancel, Mathilde; Grimard, Guy; Thuillard-Crisinel, Delphine; Moldovan, Florina; Villemure, Isabelle

2009-02-01

Mechanical loads are essential to normal bone growth, but excessive loads can lead to progressive deformities. In addition, growth plate extracellular matrix remodelling is essential to regulate the normal longitudinal bone growth process and to ensure physiological bone mineralization. In order to investigate the effects of static compression on growth plate extracellular matrix using an in vivo animal model, a loading device was used to precisely apply a compressive stress of 0.2 MPa for two weeks on the seventh caudal vertebra (Cd7) of rats during the pubertal growth spurt. Control, sham and loaded groups were studied. Growth modulation was quantified based on calcein labelling, and three matrix components (type II and X collagens, and aggrecan) were assessed using immunohistochemistry/safranin-O staining. As well, extracellular matrix components and enzymes (MMP-3 and -13, ADAMTS-4 and -5) were studied by qRT-PCR. Loading reduced Cd7 growth by 29% (p<0.05) and 15% (p=0.07) when compared to controls and shams respectively. No significant change could be observed in the mRNA expression of collagens and the proteolytic enzyme MMP-13. However, MMP-3 was significantly increased in the loaded group as compared to the control group (p<0.05). No change was observed in aggrecan and ADAMTS-4 and -5 expression. Low immunostaining for type II and X collagens was observed in 83% of the loaded rats as compared to the control rats. This in vivo study shows that, during pubertal growth spurt, two-week static compression reduced caudal vertebrae growth rates; this mechanical growth modulation occurred with decreased type II and X collagen proteins in the growth plate.

Post-treatment glenoid classification system for total shoulder arthroplasty.

PubMed

Churchill, R Sean

2012-04-01

Over the past 10 years, numerous advancements in glenoid preparation and resurfacing have occurred. Current glenoid classification systems are either focused solely on the patient's preoperative glenoid bone configuration or on the available glenoid bone stock in revision arthroplasty cases. While these systems provide value in preoperative planning, they fail to properly classify the surgical reconstruction completed. A literature review of common bone preparation methods and sources of glenoid prosthetic failure was performed. Based upon this review, a classification system for grading the status of the glenoid after prosthetic implantation was developed. A 6 category, post-treatment, glenoid classification system is proposed: type 0: no reaming; type I: glenoid reaming into but not through the subchondral bone; type II: glenoid reaming which perforates through <50% of the subchondral bone surface area; type III: glenoid reaming which perforates through >50% of the subchondral bone surface area; type IV: use of structural bone graft; and type V: use of a posterior augmented glenoid prosthesis. Types I-III are further subdivided into subtype A which have 100% bone support of the prosthesis, and subtype B which have a region of unsupported prosthesis. The classification system proposed addresses the surgical management of the glenoid during prosthetic replacement. This unique approach to classifying the glenoid following surgical intervention will allow direct follow-up comparison of similarly treated glenoid replacements. Future multicenter studies, possibly through joint registry databases, could then determine the long-term efficacy of the various glenoid preparation methods. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Neurologic aspects of microcephalic osteodysplastic primordial dwarfism type II.

PubMed

Galasso, Cinzia; Lo-Castro, Adriana; Lalli, Cristina; Cerminara, Caterina; Curatolo, Paolo

2008-06-01

Microcephalic osteodysplastic primordial dwarfism type II is a specific disorder characterized by severe intrauterine and postnatal growth retardation, acquired microcephaly, cerebrovascular abnormalities, progressive bone dysplasia, and a characteristic face. Whereas the diagnostic features of this syndrome are well-recognized, the neurologic aspects have not been clearly defined. We report on a detailed neurodevelopmental follow-up study of a new case of microcephalic osteodysplastic primordial dwarfism type II, followed from the first years of life to adolescence, and we discuss the neurocognitive features of our patient. We also review the neurologic aspects of this disorder compared with syndromes with overlapping phenotypes, such as microcephalic osteodysplastic primordial dwarfism types I and III and Seckel syndrome.

[Effects of nicotine on bone marrow stromal cells proliferation and differentiation of chondrocyte in vitro].

PubMed

Ying, Xiao-zhou; Peng, Lei; Cheng, Shao-wen; Chen, Qing-yu; Zhang, Wei; Kou, Dong-quan; Shen, Yue

2011-11-01

To examine the effects of various concentration of nicotine on bone marrow stromal cells (BMSCs) proliferation and differentiation of cartilaginous in vitro. BMSCs was obtained from femoral bone and tibia of New-Zealand albino rabbit. The cells of the 3rd generation were used in study. Different concentration of nicotine (0, 1 x 10(-7), 1 x 10(-6), 1 x 10(-5) M) were added into BMSCs. BMSCs proliferation was analyzed by MTT assay at the 1, 4, 7, 14 days. The expression of collagen type II and aggrecan as the marker genes of cartilaginous differentiation from BMSCs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Microscope showed that BMSCs transformed from round to fusiform shape. The concentration of nicotine in 1 x 10(-7), 1 x 10(-6) M had a significant positive effect on cell proliferation and the expression of type II collagen in a time-dependent manner when supplemented in commonly used induction media (P<0.05). Concentrations of nicotine in 1 x 10(-7) can promote the expression of aggrecan at the 7th day after induction,and in 1 x 10(-5) M may inhibit the expression of type II collagen and aggrecan. It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing cartilaginous differentiation capacity of BMSCs in cartilage tissue engineering.

Regulatory elements driving the expression of skeletal lineage reporters differ during bone development and adulthood.

PubMed

Stiers, Pieter-Jan; van Gastel, Nick; Moermans, Karen; Stockmans, Ingrid; Carmeliet, Geert

2017-12-01

To improve bone healing or regeneration more insight in the fate and role of the different skeletal cell types is required. Mouse models for fate mapping and lineage tracing of skeletal cells, using stage-specific promoters, have advanced our understanding of bone development, a process that is largely recapitulated during bone repair. However, validation of these models is often only performed during development, whereas proof of the activity and specificity of the used promoters during the bone regenerative process is limited. Here, we show that the regulatory elements of the 6kb collagen type II promoter are not adequate to drive gene expression during bone repair. Similarly, the 2.3kb promoter of collagen type I lacks activity in adult mice, but the 3.2kb promoter is suitable. Furthermore, Cre-mediated fate mapping allows the visualization of progeny, but this label retention may hinder to distinguish these cells from ones with active expression of the marker at later time points. Together, our results show that the lineage-specific regulatory elements driving gene expression during bone development differ from those required later in life and during bone repair, and justify validation of lineage-specific cell tracing and gene silencing strategies during fracture healing and bone regenerative applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of different rotary devices on bone repair in rabbits.

PubMed

Ribeiro Junior, Paulo Domingos; Barleto, Christiane Vespasiano; Ribeiro, Daniel Araki; Matsumoto, Mariza Akemi

2007-01-01

In oral surgery, the quality of bone repair may be influenced by several factors that can increase the morbidity of the procedure. The type of equipment used for ostectomy can directly affect bone healing. The aim of this study was to evaluate bone repair of mandible bone defects prepared in rabbits using three different rotary devices. Fifteen New Zealand rabbits were randomly assigned to 3 groups (n=5) according to type of rotary device used to create bone defects: I--pneumatic low-speed rotation engine, II--pneumatic high-speed rotation engine, and III--electric low-speed rotation engine. The anatomic pieces were surgically obtained after 2, 7 and 30 days and submitted to histological and morphometric analysis. The morphometric results were expressed as the total area of bone remodeling matrix using an image analysis system. Increases in the bone remodeling matrix were noticed with time along the course of the experiment. No statistically significant differences (p>0.05) were observed among the groups at the three sacrificing time points considering the total area of bone mineralized matrix, although the histological analysis showed a slightly advanced bone repair in group III compared to the other two groups. The findings of the present study suggest that the type of rotary device used in oral and maxillofacial surgery does not interfere with the bone repair process.

Corrective Septorhinoplasty in Acute Nasal Bone Fractures.

PubMed

Kim, Jisung; Jung, Hahn Jin; Shim, Woo Sub

2018-03-01

Closed reduction is generally recommended for acute nasal bone fractures, and rhinoplasty is considered in cases with an unsatisfactory outcome. However, concomitant rhinoplasty with fracture reduction might achieve better surgical outcomes. This study investigated the surgical techniques and outcomes in patients who underwent rhinoplasty and fracture reduction concomitantly, during the acute stage of nasal bone fracture. Forty-five patients who underwent concomitant rhinoplasty and fracture reduction were enrolled. Nasal bone fractures were classified into three major types (type I, simple fracture; type II, fracture line that mimics nasal osteotomy; and type III, comminuted fracture) based on computed tomography images and preoperative facial images. Two independent otolaryngology-head and neck surgeons evaluated the surgical outcomes and telephone based survey were made to evaluate patients satisfaction. Among 45 patients, there were 39 males and 6 females. Type I was the commonest type of fracture with 18 patients (40%), while the most frequently used surgical technique for corrective surgery was dorsal augmentation with 44 patients (97.8%). The mean visual analogue scale satisfaction score of the surgeons and patients were 7.62 and 8, respectively, with no significant differences between fracture types. Concomitant rhinoplasty with fracture reduction can be performed for acute nasal bone fracture patients, and it might lead to better aesthetic outcomes.

Effect of single- and double-row rotator cuff repair at the tendon-to-bone interface: preliminary results using an in vivo sheep model.

PubMed

Baums, M H; Schminke, B; Posmyk, A; Miosge, N; Klinger, H-M; Lakemeier, S

2015-01-01

The clinical superiority of the double-row technique is still a subject of controversial debate in rotator cuff repair. We hypothesised that the expression of different collagen types will differ between double-row and single-row rotator cuff repair indicating a faster healing response by the double-row technique. Twenty-four mature female sheep were randomly assembled to two different groups in which a surgically created acute infraspinatus tendon tear was fixed using either a modified single- or double-row repair technique. Shoulder joints from female sheep cadavers of identical age, bone maturity, and weight served as untreated control cluster. Expression of type I, II, and III collagen was observed in the tendon-to-bone junction along with recovering changes in the fibrocartilage zone after immunohistological tissue staining at 1, 2, 3, 6, 12, and 26 weeks postoperatively. Expression of type III collagen remained positive until 6 weeks after surgery in the double-row group, whereas it was detectable for 12 weeks in the single-row group. In both groups, type I collagen expression increased after 12 weeks. Type II collagen expression was increased after 12 weeks in the double-row versus single-row group. Clusters of chondrocytes were only visible between week 6 and 12 in the double-row group. The study demonstrates differences regarding the expression of type I and type III collagen in the tendon-to-bone junction following double-row rotator cuff repair compared to single-row repair. The healing response in this acute repair model is faster in the double-row group during the investigated healing period.

HLA-typing analysis following allogeneic bone grafting for sinus lifting.

PubMed

Piaia, Marcelo; Bub, Carolina Bonet; Succi, Guilherme de Menezes; Torres, Margareth; Costa, Thiago Henrique; Pinheiro, Fabricio Costa; Napimoga, Marcelo Henrique

2017-03-01

According to the Brazilian Association of Organ Transplants, in 2015, 19,408 bone transplants were performed in Brazil, over 90% by Dental Surgeons. The surgical technique itself has a respectable number of reports regarding its clinical efficacy, as measured by long-term survival of dental implants in grafted areas. Uncertainty remains, however, as to whether fresh frozen grafts from human bone donors remain immunologically innocuous in the body of the host. Six male with no previous medical history of note, including systemic diseases, surgery or blood transfusion were selected. These patients underwent reconstructive procedures (sinus lifting) using fresh frozen human bone from a tissue bank. All patients had venous blood samples collected prior to surgery and 6 months after the procedure. Anti-HLA analysis for the detection of HLA (human leukocyte antigen) antibodies was performed using methods such as the LABScreen PRA Class I and Class II, LABScreen Single Antigen Class I and Class II, Luminex Platform. Reactive individuals to the screening tests (LABScreen PRA) were further investigated to determine the specificity of the antibodies detected (LABScreen Single Antigen) with a cutoff value of median fluorescence intensity ≥500. As a result, it was observed that two patients (33%) were positive in screening tests, one presenting with anti-HLA Class I and II sensitization and the other with anti-HLA class II. The specificity analysis showed that the patients sensitized to HLA class II presented 4 specificities, 3 of which immunologically relevant. In the second individual, 23 specificities were identified, 6 of which immunologically important for HLA class I and 4 specificities for HLA class II, 3 of these were immunologically important. All specificities detected had average fluorescence. These findings are suggestive that sinus-lifting procedures with allogeneic bone can induce immunological sensitization.

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis.

PubMed

Junbo, Wang; Sijia, Liu; Hongying, Chen; Lei, Liu; Pu, Wang

2017-06-15

Whole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)-induced knee osteoarthritisrabbit model. Ninety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed. After 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group. Our data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Characterizing the Lower Paleolithic bone industry from Schöningen 12 II: A multi-proxy study.

PubMed

Julien, Marie-Anne; Hardy, Bruce; Stahlschmidt, Mareike C; Urban, Brigitte; Serangeli, Jordi; Conard, Nicholas J

2015-12-01

Although preservation of Paleolithic faunal assemblages from open-air settings is often poor, the Lower Paleolithic sites of Schöningen provide exceptionally well-preserved mammalian faunal material for investigating hominin/animal relationships. Pleistocene fossil assemblages, however, usually reflect a complex taphonomic history in which natural and anthropogenic processes are often superimposed. A number of examples of osseous finds that resemble tools were recently discovered in the MIS 9 deposits of Schöningen 12 II. Non-anthropogenic agents are known to produce surface modifications mimicking human artifacts and the identification of osseous remains used and/or deliberately modified by ancient hominins is often controversial in such old contexts. Multiple lines of evidence are thus useful for distinguishing between osseous artifacts and "eco-facts". In this paper, the recognition of the use of bone for different technological purposes by late Middle Pleistocene hominins is addressed through a multi-proxy study combining geoarcheology, bone taphonomy, zooarcheology, and use-wear analysis. This allowed the identification of the processes and agents responsible for the formation and modification of the different bone assemblages of Schöningen 12 II. Our analysis points to different types of bones having been likely used as tools. These results expand the diversity of the organic technological repertoire of the Middle Pleistocene hominins, making Schöningen 12 II a remarkable new source of information on osseous technology long before the Upper Paleolithic, the period traditionally viewed as the start of the systematic use of bone tools. Together with other observations of bone tools documented during the Lower and Middle Paleolithic, the results from Schöningen show that archeologists may have underestimated the diversity and importance of osseous technology among archaic hominins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Wrapping grafting for congenital pseudarthrosis of the tibia

PubMed Central

Yan, An; Mei, Hai-Bo; Liu, Kun; Wu, Jiang-Yan; Tang, Jin; Zhu, Guang-Hui; Ye, Wei-Hua

2017-01-01

Abstract Objective: Treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge. The autogenic iliac bone graft is important consistent of treatment for CPT. The purpose of this study was to investigate the role of wrapping autogenic iliac bone graft in improvement of the curing opportunities of CPT. Methods: We combined Ilizarov fixator with intramedullary rodding of the tibia and wrapping autogenic iliac bone graft for treatment 51 cases of CPT between 2007 and 2010. The mean age is 3.2 years at index operation, of which 31 patients (61%) were below 3 years old. According to Crawford classification, 5 tibia had type-II morphology; 3, type-III; 43, type-IV. Results: In the postoperative follow-up of 3.5 months (range from 3 to 4.5 months), all cases were found that the bone graft sites of pseudarthrosis of the tibia showed a significant augmentation and spindle-shaped expansion as obvious change. All cases of this series have been followed-up, average followed-up time were 1.6 years (range from 7 to 3.1 years), of which 19 cases were more than 2 years. The average time of removed the Ilizarov ring fixator was 3.5 months (range from 3 to 4.5 months). According to Johnston Clinical evaluation system, 26 cases had grade I, 21 cases, grade II, 4 cases, grade III. Following the Ohnishi X-ray evaluation criteria, union of pseudarthrosis of the tibia were 42 cases, delayed union 5 cases, nonunion 4 cases. Conclusion: Autogenic iliac bone graft is able to offer the activity of osteoblasts and osteogenesis induced by bone morphogenetic protein (BMP) and glycoprotein, meanwhile enclosing bone graft could help keep cancellous bone fragments in close contact around pseudarthrosis of the tibia, allowing the formation of high concentration of glycoprotein and BMP induced by chemical factors because of established the sealing environment in location, all of which could enhance the healing of pseudarthrosis of the tibia. PMID:29310362

Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients.

PubMed

Sorva, A; Välimäki, M; Risteli, J; Risteli, L; Elfving, S; Takkunen, H; Tilvis, R

1994-12-01

Chronic immobilization could markedly affect calcium and bone metabolism in elderly people. To investigate this, and to test the theory of 'type II' osteoporosis in bedridden elderly patients with low vitamin D status, 55 such subjects were examined. Serum concentrations of ionized calcium (Ca++), intact parathyrin (PTH) and two novel markers of bone collagen formation (carboxyterminal propeptide of type I procollagen; PICP) and resorption (carboxyterminal crosslinked telopeptide of type I collagen; ICTP) were measured. The effects on these parameters after 40 weeks of supplementation with vitamin D (1000 IU d-1) and/or calcium (1 g d-1) were subsequently prospectively evaluated. Despite low (mean 11.6 nmoll-1) serum 25-hydroxyvitamin D levels (25-OHD), those of 1,25-dihydroxy-vitamin D (1,25-(OH)2D) were mostly normal. Neither correlated with Ca++ or PTH. PTH correlated negatively not only with Ca++ (r = -0.328, P < 0.05) but also with ICTP (r = -0.306, P < 0.05). Mean PICP was normal but ICTP was elevated and tended to correlate positively with Ca++ (r = 0.268, P = 0.06). Vitamin D supplementation did not change PICP or ICTP considerably, despite slightly increased 1,25-(OH)2D and slightly decreased PTH. Ca++ values were normal and remained stable. In conclusion, Ca++ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects. Furthermore, the results suggest that the increased bone resorption is not due to 'type II' secondary hyperparathyroidism; rather the resorption is primarily increased. Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided.

Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis.

PubMed

Hayami, Tadashi; Zhuo, Ya; Wesolowski, Gregg A; Pickarski, Maureen; Duong, Le T

2012-06-01

To investigate the disease modifying effects of cathepsin K (CatK) inhibitor L-006235 compared to alendronate (ALN) in two preclinical models of osteoarthritis (OA). Skeletally mature rabbits underwent sham or anterior cruciate ligament transection (ACLT)-surgery and were treated with L-006235 (L-235, 10 mg/kg or 50 mg/kg, p.o., daily) or ALN (0.6 mg/kg, s.c., weekly) for 8-weeks. ACLT joint instability was also induced in CatK(-/-) versus wild type (wt) mice and treated for 16-weeks. Changes in cartilage degeneration, subchondral bone volume and osteophyte area were determined by histology and μ-CT. Collagen type I helical peptide (HP-I), a bone resorption marker and collagen type II C-telopeptide (CTX-II), a cartilage degradation marker were measured. L-235 (50 mg/kg) and ALN treatment resulted in significant chondroprotective effects, reducing CTX-II by 60% and the histological Mankin score for cartilage damage by 46% in the ACLT-rabbits. Both doses of L-235 were more potent than ALN in protecting against focal subchondral bone loss, and reducing HP-I by 70% compared to vehicle. L-235 (50 mg/kg) and ALN significantly reduced osteophyte formation in histomorphometric analysis by 55%. The Mankin score in ACLT-CatK(-/-) mice was ~2.5-fold lower than the ACLT-wt mice and was not different from sham-CatK(-/-). Osteophyte development was not different among the groups. Inhibition of CatK provides significant benefits in ACLT-model of OA, including: 1) protection of subchondral bone integrity, 2) protection against cartilage degradation and 3) reduced osteophytosis. Preclinical evidence supports the role of CatK as a potential therapeutic target for the treatment of OA. Copyright © 2012 Elsevier Inc. All rights reserved.

Surgical correction of bilateral metacarpophalangeal valgus with curved osteotomies and type II external skeletal fixation in a seven-month-old alpaca.

PubMed

Schoonover, Mike J; Whitfield, Chase T; Rochat, Mark C; Streeter, Robert N; Sippel, Kate

2016-09-20

To report the successful surgical correction of severe bilateral metacarpophalangeal valgus angular limb deformities in a seven-month-old intact male alpaca cria using curved osteotomies stabilized with type II external skeletal fixation. Using a 21 mm crescentic shaped oscillating saw blade, bilateral osteotomies were performed in the distal metaphyses of the fused third and fourth metacarpal bones to correct valgus angular limb deformity of the metacarpophalangeal joints. Axial alignment of each limb was achieved by medially rotating the distal metacarpus in the frontal plane along the curved osteotomies. The osteotomies were stabilized using type II external skeletal fixators. The alpaca was immediately weight-bearing following the surgical procedure and no to minimal lameness was observed during healing of the osteotomies. Evaluation at five and 10 months following the surgery demonstrated acceptable axial alignment in the left forelimb while moderate to severe varus deformity (overcorrection) was observed in the right. Curved osteotomy of the distal metacarpus stabilized with type II external skeletal fixation can provide a favourable outcome in older alpaca crias affected with metacarpophalangeal angular limb deformities. Placement of the distal transfixation pins relative to the metacarpal physes should be carefully evaluated as overcorrection is possible, especially if growthpotential remains in only one physis of the fused third and fourth metacarpal bones.

Chondroprotective effects of zoledronic acid on articular cartilage in dogs with experimentally induced osteoarthritis.

PubMed

Dearmin, Michael G; Trumble, Troy N; García, Anapatricia; Chambers, Jon N; Budsberg, Steven C

2014-04-01

To assess effects of zoledronic acid on biomarkers, radiographic scores, and gross articular cartilage changes in dogs with induced osteoarthritis. 21 purpose-bred hound-type dogs. The left stifle joint of each dog was examined arthroscopically to determine initial articular cartilage status, which was followed by cranial cruciate ligament (CrCL) transection to induce osteoarthritis. Dogs were assigned to 3 groups (control group, low dose [10 μg of zoledronic acid/kg], or high dose [25 μg of zoledronic acid/kg). Treatments were administered SC every 3 months for 1 year beginning the day after CrCL transection. Serum and synovial fluid samples and radiographs were obtained 0, 1, 3, 6, 9, and 12 months after transection. At 12 months, each joint was scored for cartilage defects. Serum and synovial fluid biomarkers of bone and cartilage turnover (bone-specific alkaline phosphatase, type I and II collagen, carboxy-propeptide of type II collagen, and chondroitin sulfate 846) were analyzed with ELISAs. The high-dose group had fewer total articular defects and lower severity scores in CrCL-transected stifle joints than did the control group. In addition, the high-dose group had significantly less change in collagenase cleavage of type I or II collagen in the synovial fluid at 1 and 3 months after CrCL transection than did the control group and also had greater changes in bone-specific alkaline phosphatase in synovial fluid at 3 months after CrCL transection than did the control group. Zoledronic acid had a chondroprotective effect in dogs with a transected CrCL.

Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review.

PubMed

Castelo-Branco, C; Dávila Guardia, J

2015-02-01

The ossein-hydroxyapatite complex (OHC) is a microcrystalline form of calcium which provides a number of additional minerals (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I collagen, type I insulin growth factor I and II, transforming growth factor beta) associated with bone metabolism. The objective of this review is to examine the role of OHC in preventing bone loss in different conditions. A review of clinical trials assessing the relationship between OHC and bone loss was made using the following data sources: Medline (from 1966 to December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to December 2013), contact with companies marketing the supplements studied, and reference lists. Different randomized, clinical trials and meta-analysis suggest that OHC is more effective than calcium supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss. In addition, OHC improves pain symptoms and accelerates fracture consolidation in patients with osteopenia or osteoporosis. The ossein-hydroxyapatite complex is significantly more effective in preventing bone loss than calcium carbonate.

Evaluation of secondary alveolar bone grafting outcomes performed after canine eruption in complete unilateral cleft lip and palate.

PubMed

Lorenzoni, Diego Coelho; Janson, Guilherme; Bastos, Juliana Cunha; Carvalho, Roberta Martinelli; Bastos, José Carlos; de Cássia Moura Carvalho Lauris, Rita; Henriques, José Fernando Castanha; Ozawa, Terumi Okada

2017-01-01

Evaluate the results of secondary alveolar bone grafting (SABG) in patients with complete unilateral cleft lip and palate (UCLP), operated after permanent canine eruption (CE). Seventy-four periapical radiographs from patients with complete UCLP (mean age 14 years) submitted to SABG were retrospectively analyzed for the amount of bone in the cleft site through the Bergland and Chelsea scales. Of the cases, 47.3 % was classified as Bergland type I and Chelsea type A, 35.2 % as type II/C, 6.7 % as type III/D, and 10.8 % as type IV/failure. When the canine was moved into the grafted area, the success rate (type I/A) was 56.8 %; for cases in which the space was maintained for an implant or prosthetic finishing, the index was 45.8 %; however, this difference was not statistically significant. Even in advanced ages, after permanent canine eruption, SABG can be considered a highly successful procedure. This research shows good results of secondary alveolar bone grafting performed in patients with unilateral complete cleft lip and palate, even when it was performed after eruption of the permanent canine in the cleft area.

Characterization of collagen II fibrils containing biglycan and their effect as a coating on osteoblast adhesion and proliferation.

PubMed

Douglas, Timothy; Heinemann, Sascha; Hempel, Ute; Mietrach, Carolin; Knieb, Christiane; Bierbaum, Susanne; Scharnweber, Dieter; Worch, Hartmut

2008-04-01

Collagen has been used as a coating material for titanium-based implants for bone contact and as a component of scaffolds for bone tissue engineering. In general collagen type I has been used, however very little attention has been focussed on collagen type II. Collagen-based coatings and scaffolds have been enhanced by the incorporation of the glycosaminoglycan chondroitin sulphate (CS), however the proteglycan biglycan, which is found in bone and contains glycosaminoglycan chains consisting of CS, has not been used as a biomaterial component. The study had the following aims: firstly, five different collagen II preparations were compared with regard to their ability to bind CS and biglycan and the changes in fibril morphology thereby induced. Secondly, the effects of biglycan on the adhesion of primary rat osteoblasts (rO) as well as the proliferation of rO, primary human osteoblasts (hO) and the osteoblast-like cell line 7F2 were studied by culturing the cells on surfaces coated with collagen II fibrils containing biglycan. Fibrils of the collagen II preparation which bound the most biglycan were used to coat titanium surfaces. Bare titanium, titanium coated with collagen II fibrils and titanium coated with collagen II fibrils containing biglycan were compared. It was found that different collagen II preparations showed different affinities for CS and biglycan. In four of the five preparations tested, biglycan reduced fibril diameter, however the ability of a preparation to bind more biglycan did not appear to lead to a greater reduction in fibril diameter. Fibrils containing biglycan promoted the formation of focal adhesions by rO and significantly enhanced the proliferation of hO but not of rO or 7F2 cells. These results should encourage further investigation of biglycan as a component of collagen-based scaffolds and/or coatings.

Histological evolution of the regenerate during bone transport: an experimental study in sheep.

PubMed

López-Pliego, Esperanza Macarena; Giráldez-Sánchez, Miguel Ángel; Mora-Macías, Juan; Reina-Romo, Esther; Domínguez, Jaime

2016-09-01

Bone transport (BT) for segmentary bone defects is a well-known technique as it enables correction with new bone formation, which is similar to the previous bone. Despite the high number of experimental studies of distraction osteogenesis in bone lengthening, the types of ossification and histological changes that occur in the regenerate of the bone transport process remain controversial. The aim of this study is to provide the complete evolution of tissues and the types of ossification in the regenerate during the different phases of bone formation after BT until the end of the remodelling period. A histological study was performed using ten adult sheep that were submitted to BT. The types of ossification as well as the evolution of different tissues in the regenerate were determined using histomorphometry and inmunohistochemical studies. The evolution of trabeculae thickness, osteoblast and osteoclast densities, relationship between collagen types and changes in vascularization were also studied. Ossification was primarily intramembranous, with some focus of endochondral ossification in isolated animals. The cell counts showed a progression of cellular activity from the periphery to the centre, presenting the same progression as the growth of bone trabeculae, whose trabeculae thickness was quadrupled at the end of remodelling. Inmunohistochemical studies confirmed the prevalence of type I collagen and the ratio of the Type I/Type II collagen ratio was found to be 2.48. The percentages of the vascularized areas were proximally higher than distally in all animals, but distal zone obtained higher rates than the central region. Bone transport regenerate exhibits a centripetal ossification model and a mixed pattern with predominance of intramembranous over endochondral ossification. The data obtained resemble partially to those found in models of bone lengthening applied to large animals. This study provides a detailed structural characterization of the newly formed tissue, which may help to explain the development of the regenerate of bone transport in humans. It will also serve for future mechanobiological models that may aid research on the effect of loading or distractor stiffness in clinical results. © 2016 Elsevier Ltd. All rights reserved.

Evaluation of Bone Thickness and Density in the Lower Incisors' Region in Adults with Different Types of Skeletal Malocclusion using Cone-beam Computed Tomography.

PubMed

Al-Masri, Maram M N; Ajaj, Mowaffak A; Hajeer, Mohammad Y; Al-Eed, Muataz S

2015-08-01

To evaluate the bone thickness and density in the lower incisors' region in orthodontically untreated adults, and to examine any possible relationship between thickness and density in different skeletal patterns using cone-beam computed tomography (CBCT). The CBCT records of 48 patients were obtained from the archive of orthodontic department comprising three groups of malocclusion (class I, II and III) with 16 patients in each group. Using OnDemand 3D software, sagittal sections were made for each lower incisor. Thicknesses and densities were measured at three levels of the root (cervical, middle and apical regions) from the labial and lingual sides. Accuracy and reliability tests were undertaken to assess the intraobserver reliability and to detect systematic error. Pearson correlation coefficients were calculated and one-way analysis of variance (ANOVA) was employed to detect significant differences among the three groups of skeletal malocclusion. Apical buccal thickness (ABT) in the four incisors was higher in class II and I patients than in class III patients (p < 0.05). There were significant differences between buccal and lingual surfaces at the apical and middle regions only in class II and III patients. Statistical differences were found between class I and II patients for the cervical buccal density (CBD) and between class II and III patients for apical buccal density (ABD). Relationship between bone thickness and density values ranged from strong at the cervical regions to weak at the apical regions. Sagittal skeletal patterns affect apical bone thickness and density at buccal surfaces of the four lower incisors' roots. Alveolar bone thickness and density increased from the cervical to the apical regions.

Experimental study on differences in clivus chordoma bone invasion: an iTRAQ-based quantitative proteomic analysis.

PubMed

Wu, Zhen; Wang, Liang; Guo, Zhengguang; Wang, Ke; Zhang, Yang; Tian, Kaibing; Zhang, Junting; Sun, Wei; Yu, Chunjiang

2015-01-01

Although a bone tumor, significant differences in the extent of bone invasion exist in skull base chordoma, which directly affect the extent of surgical resection, and have an impact on its prognosis. However, the underlying mechanism of the phenomenon is not clearly understood. Therefore, we used an iTRAQ-based quantitative proteomics strategy to identify potential molecular signatures, and to find predictive markers of discrepancy in bone invasion of clivus chordoma. According to bone invasive classification criteria, 35 specimens of clivus chordoma were calssified to be either endophytic type (Type I) or exophytic type (Type II). An initial screening of six specimens of endophytic type and six of exophytic was performed, and 250 differentially expressed proteins were identified. Through the GO and IPA analysis, we found evidence that the expression of inflammatory activity-associated proteins up-regulated in endophytic type, whereas the expression of cell motility-associated proteins up-regulated in exophytic ones. Moreover, TGFβ1 and mTOR signal pathway seemed to be related with bone invasion. Thus, TGFβ1, PI3K, Akt, mTOR, and PTEN were validated in the following 23 samples by immune histochemistry and Western blot. The expression levels of TGFβ1 and PTEN were significantly lower in the endophytic type than in the exophytic ones. It was found that TGFβ1 may play an important role in its bone invasion. The mechanisms may be related with conducting an increased inflammatory cell response and a decline in cytoskeletal protein expression. PTEN is confirmed to be associated with the degree of bone invasion. The PI3K/AKT/mTOR signaling pathway might be associated with the bone invasion, but still needs a larger sample size to be verified These results, for the first time, not only demonstrate the biological changes that occur in different growth patterns from the perspective of proteomics, but also provide novel markers that may help to reveal the mechanisms behind clivus chordomas.

Acetabular Reconstruction With Femoral Head Autograft After Intraarticular Resection of Periacetabular Tumors is Durable at Short-term Followup.

PubMed

Tang, Xiaodong; Guo, Wei; Yang, Rongli; Yan, Taiqiang; Tang, Shun; Li, Dasen

2017-12-01

Pelvic reconstruction after periacetabular tumor resection is technically difficult and characterized by a high complication rate. Although endoprosthetic replacement can result in immediate postoperative functional recovery, biologic reconstructions with autograft may provide an enhanced prognosis in patients with long-term survival; however, little has been published regarding this approach. We therefore wished to evaluate whether whole-bulk femoral head autograft that is not contaminated by tumor can be used to reconstruct segmental bone defects after intraarticular resection of periacetabular tumors. In a pilot study, we evaluated (1) local tumor control, (2) complications, and (3) postoperative function as measured by the Musculoskeletal Tumor Society score. Between 2009 and 2015, we treated 13 patients with periacetabular malignant or aggressive benign tumors with en bloc resection, bulk femoral head autograft, and cemented THA (with or without a titanium acetabular reconstruction cup), and all were included for analysis here. During that time, the general indications for this approach were (1) patients anticipated to have a good oncologic prognosis and adequate surgical margins to allow this approach, (2) patients whose pelvic bone defects did not exceed two types (Types I + II or Types II + III as defined by Enneking and Dunham), and (3) patients whose medical insurance would not cover what otherwise might have been a pelvic tumor prosthesis. During this period, another 91 patients were treated with pelvic prosthetic replacement, which was our preferred approach. Median followup in this study was 36 months (range, 24-99 months among surviving patients; one patient died 8 months after surgery); no patients were lost to followup. Bone defects were Types II + III in five patients, and Types I + II in eight. After intraarticular resection, ipsilateral femoral head autograft combined with THA was used to reconstruct the segmental bone defect of the acetabulum. In patients with Types I + II resections, the connection between the sacrum and the acetabulum was reestablished with a fibular autograft or a titanium cage filled with dried bone-allograft particles which was enhanced by using a pedicle screw and rod system. Functional evaluation was done in 11 patients who remained alive and maintained the femoral head autograft at final followup; one other patient received secondary resection involving removal of the femoral head autograft and internal fixation, and was excluded from functional evaluation. Endpoints were assessed by chart review. Two patients experienced local tumor recurrence. Finally, eight patients did not show signs of the disease, one patient died of disease for local and distant tumor relapse, and four patients survived, but still had the disease. Three of these four patients had distant metastases without local recurrence and one had local control after secondary resection but still experienced system relapse. We observed the following complications: hematoma (one patient; treated surgically with hematoma clearance), delayed wound healing (one patient; treated by débridement), deep vein thrombosis (one patient), and hip dislocation (one patient; treated with open reduction). The median 1993 Musculoskeletal Tumor Society score was 83% (25 of 30 points; range, 19-29 points), and all patients were community ambulators; one used a cane, three used a walker, and nine did not use any assistive devices. In this small series at short-term followup, we found that reconstruction of segmental bone defects after intraarticular resection of periacetabular tumors with femoral head autograft does not appear to impede local tumor control; complications were in the range of what might be expected in a series of large pelvic reconstructions, and postoperative function was generally good. Level IV, therapeutic study.

Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface.

PubMed

Zhou, Yiqin; Zhang, Jianying; Yang, Jinsong; Narava, Manoj; Zhao, Guangyi; Yuan, Ting; Wu, Haishan; Zheng, Nigel; Hogan, MaCalus V; Wang, James H-C

2017-12-01

Treatment of tendon-bone junction injuries is a challenge because tendon-bone interface often heals poorly and the fibrocartilage zone, which reduces stress concentration, at the interface is not formed. In this study, we used a compound called kartogenin (KGN) with platelet-rich plasma (PRP) to induce the formation of fibrocartilage zone in a rat tendon graft-bone tunnel model. The experimental rats received KGN-PRP or PRP injections in the tendon graft-bone tunnel interface. The control group received saline. After 4, 8 and 12 weeks, Safranin O staining of the tendon graft-bone tunnels revealed abundant proteoglycans in the KGN-PRP group indicating the formation of cartilage-like transition zone. Immunohistochemical and immuno-fluorescence staining revealed collagen types I (Col-I) and II (Col-II) in the newly formed fibrocartilage zone. Both fibrocartilage zone formation and maturation were healing time dependent. In contrast, the PRP and saline control groups had no cartilage-like tissues and minimal Col-I and Col-II staining. Some gaps were also present in the saline control group. Finally, pull-out strength in the KGN-PRP-treated group at 8 weeks was 1.4-fold higher than the PRP-treated group and 1.6-fold higher than the saline control group. These findings indicate that KGN, with PRP as a carrier, promotes the formation of fibrocartilage zone between the tendon graft and bone interface. Thus, KGN-PRP may be used as a convenient cell-free therapy in clinics to promote fibrocartilage zone formation in rotator calf repair and anterior cruciate ligament reconstruction, thereby enhancing the mechanical strength of the tendon-bone interface and hence the clinical outcome of these procedures. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Pathologic Changes of the Peripheral Vestibular System Secondary to Chronic Otitis Media.

PubMed

da Costa Monsanto, Rafael; Erdil, Mehmet; Pauna, Henrique F; Kwon, Geeyoun; Schachern, Patricia A; Tsuprun, Vladimir; Paparella, Michael M; Cureoglu, Sebahattin

2016-09-01

To evaluate the histopathologic changes of dark, transitional, and hair cells of the vestibular system in human temporal bones from patients with chronic otitis media. Comparative human temporal bone study. Otopathology laboratory. To compare the density of vestibular dark, transitional, and hair cells in temporal bones with and without chronic otitis media, we used differential interference contrast microscopy. In the chronic otitis media group (as compared with the age-matched control group), the density of type I and type II hair cells was significantly decreased in the lateral semicircular canal, saccule, and utricle (P < .05). The density of type I cells was also significantly decreased in the chronic otitis media group in the posterior semicircular canal (P = .005), but that of type II cells was not (P = .168). The mean number of dark cells was significantly decreased in the chronic otitis media group in the lateral semicircular canal (P = .014) and in the posterior semicircular canal (P = .002). We observed no statistically significant difference in the density of transitional cells between the 2 groups (P > .1). The findings of our study suggest that the decrease in the number of vestibular sensory cells and dark cells could be the cause of the clinical symptoms of imbalance of some patients with chronic otitis media. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Association of Angiotensin Converting Enzyme I/D and α-actinin-3 R577X Genotypes with Growth Factors and Physical Fitness in Korean Children

PubMed Central

Ahn, Nayoung; Cheun, Wookwang; Byun, Jayoung; Joo, Youngsik

2015-01-01

This study analyzed the differences in aerobic and anaerobic exercise ability and growth-related indicators, depending on the polymorphism of the ACE and the ACTN3 genes, to understand the genetic influence of exercise ability in the growth process of children. The subjects of the study consisted of elementary school students (n=856, age 10.32±0.07 yr). The anthropometric parameters, physical fitness and growth factors were compared among groups of the ACE I/D or the ACTN3 R577X polymorphisms. There were no significant differences between the anthropometric parameters, physical fitness and growth factors for the ACE gene ID or the ACTN3 gene R577X polymorphism. However, the DD type of ACE gene was highest in the side step test (p<0.05), and the DD type was significantly higher than the II+ID type (p<0.05) in the early bone age. The combined group of the ACE gene II+ID and the ACTN3 gene XX type significantly showed lower early bone age (p< 0.05). This study did not find any individual or compounding effects of the polymorphism in the ACE I/D or the ACTN3 R577X polymorphisms on the anthropometric parameters, physical fitness and growth factors of Korean children. However, the exercise experience and the DD type of the ACE gene may affect the early maturity of the bones. PMID:25729275

Management of fibular hemimelia using the Ilizarov method at Siriraj Hospital in Thailand.

PubMed

Unprasert, Prangthong; Kaewpornsawan, Kamolporn; Chotigavanichaya, Chatupon; Eamsobhana, Perajit

2014-09-01

Fibular hemimelia is one of the most common congenital longitudinal bone deficiencies. Previous treatment protocols called for amputation of the deficient limb; while others made attempts to save the limb. The objective of treatment is to restore function and achieve patient satisfaction. The authors evaluated the outcomes of the Ilizarov technique for the treatment of leg-length discrepancy and bone associated deformities in patients with fibular hemimelia. The present study also evaluated and assessed complications, knee and ankle function, and patient satisfaction with the treatment. Nine patients with fibular hemimelia who underwent tibial lengthening using the Ilizarov method were reviewed in the present study. Initial condition data, including age, gender type offibular hemimelia, initial limb-length discrepancy, predicted limb-length discrepancy, and the data were collected and analyzed. Activity level, patient satisfaction, complications, and residual leg-length discrepancy were assessed at the end of treatment. According to Achterman and Kalamchi classification, there were 4 patients with Type IA, 3 patients with Type IB, and 2 patients with Type II. In Type IA, the affected leg-length discrepancy and mean age at the initial treatment were 3.25 cm and 7.75 years, respectively. In type IB, the affected leg-length discrepancy and mean age at the initial treatment were 5.83 cm and 4.3 years, respectively. In Type II, the affected leg-length discrepancy and mean age at the initial treatment were 5.5 cm and 5 years, respectively. The mean follow-up was 5 years (range: 7-10). The mean lengthening was 7.52 cm (range: 4-13). The lengthening index was 1.28 mo/cm. The mean residual leg-length discrepancy was 0.94 cm. There was ankle joint stiffness and mild equinous foot in type II cases, but patients could walk well without gait aid. No patients were experiencing pain by the end of treatment. All patients expressed satisfaction with this technique. The Ilizarov technique for bone lengthening of the tibia has shown satisfactory results in the treatment of all types of congenital fibular hemimelia and should be considered an attractive alternative to amputation, as measureable functional improvement can be expected.

Fkbp10 Deletion in Osteoblasts leads to Qualitative Defects in Bone

PubMed Central

Lietman, Caressa D.; Lim, Joohyun; Grafe, Ingo; Chen, Yuqing; Ding, Hao; Bi, Xiaohong; Ambrose, Catherine G.; Fratzl-Zelman, Nadja; Roschger, Paul; Klaushofer, Klaus; Wagermaier, Wolfgang; Schmidt, Ingo; Fratzl, Peter; Rai, Jyoti; Weis, MaryAnn; Eyre, David; Keene, Douglas R.; Krakow, Deborah; Lee, Brendan H.

2017-01-01

Osteogenesis Imperfecta (OI), also known as brittle bone disease, displays a spectrum of clinical severity from mild (OI type I) to severe early lethality (OI type II), with clinical features including low bone mass, fractures and deformities. Mutations in the FK506 Binding Protein 10 (FKBP10), gene encoding the 65KDa protein FKBP65, cause a recessive form of OI and Bruck syndrome, the latter being characterized by joint contractures in addition to low bone mass. We previously showed that Fkbp10 expression is limited to bone, tendon and ligaments in postnatal tissues. Furthermore, in both patients and Fkbp10 knockout mice, collagen telopeptide hydroxylysine crosslinking is dramatically reduced. To further characterize the bone specific contributions of Fkbp10, we conditionally ablated FKBP65 in Fkbp10fl/fl mice (Mus musculus; C57BL/6) using the osteoblast specific Col1a1 2.3kb Cre recombinase. Using μCT, histomorphometry and quantitative backscattered electron imaging, we found minimal alterations in the quantity of bone and no differences in the degree of bone matrix mineralization in this model. However, mass spectroscopy of bone collagen demonstrated a decrease in mature, hydroxylysine-aldehyde crosslinking. Furthermore, bone of mutant mice exhibits a reduction in mineral-to-matrix ratio and in crystal size as shown by Raman spectroscopy and small angle x-ray scattering, respectively. Importantly, abnormalities in bone quality were associated with impaired bone biomechanical strength in mutant femurs compared with those of wild type littermates. Taken together, these data suggest that the altered collagen crosslinking through Fkbp10 ablation in osteoblasts primarily leads to a qualitative defect in the skeleton. PMID:28206698

A Phase II Trial on the Effect of Low-Dose versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1)

DTIC Science & Technology

2013-10-01

MD, PhD CONTRACTING ORGANIZATION: University of Utah REPORT DATE : October 2013 TYPE OF REPORT: Annual PREPARED FOR: U.S...of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE ...October 2013 2. REPORT TYPE Annual 3. DATES COVERED 15 September 2012-14 September 2013 4. TITLE AND SUBTITLE A Phase II Trial on the Effect of

ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats.

PubMed

Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

2017-08-01

The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis. 8 weeks after the surgical procedures, captopril was administered orally (40mgkg -1 d -1 ), while the specific Mas receptor blocker (A-779) was delivered at infusion rate of 400ngkg -1 min -1 for 6 weeks. Bone metabolic markers were measured in serum and urine. Minerals concentrations were quantified in serum, urine and femoral bones by inductive coupled plasma mass spectroscopy (ICP-MS). Trabecular and cortical morphometry was analyzed in the right distal femurs using micro-CT. Finally, the expressions of RAS peptides, enzymes and receptors along with the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were determined femurs heads. OVX animals markedly showed altered bone metabolism and mineralization along with disturbed bone micro-structure. Captopril significantly restored the metabolic bone bio-markers and corrected Ca 2+ and P values in urine and bones of estrogen deficient rats. Moreover, the trabecular and cortical morphometric features were repaired by captopril in OVX groups. Captopril also improved the expressions of ACE-2, Ang1-7, Mas and OPG, while abolished OVX-induced up-regulation of ACE-1, AngII, Ang type 1 receptor (AT1R) and RANKL. Inhibition of Ang1-7 cascade by A-779 significantly eradicated captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restored OVX effects on RANKL expression and ACE-1/AngII/AT1R cascade and down-regulated OPG expression and ACE-2/Ang1-7/Mas pathway. In line with the clinical observations of the bone-preservative properties following ACE-1 inhibition, local activation of ACE-2/Ang1-7/Mas signaling and suppressed osteoclastogenesis seem responsible for the osteo-preservative effect of captopril, which could offers a potential therapeutic value in treatment of disabling bone and skeletal muscular diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Novel use of gamma correction for precise (99m)Tc-HDP pinhole bone scan diagnosis and classification of knee occult fractures.

PubMed

Bahk, Yong-Whee; Jeon, Ho-Seung; Kim, Jang Min; Park, Jung Mee; Chung, Yong-An; Kim, E Edmund; Kim, Sung-Hoon; Chung, Soo-Kyo

2010-08-01

The aim of this study was to introduce gamma correction pinhole bone scan (GCPBS) to depict specific signs of knee occult fractures (OF) on (99m)Tc-hydroxydiphosphonate (HDP) scan. Thirty-six cases of six different types of knee OF in 27 consecutive patients (male = 20, female = 7, and age = 18-86 years) were enrolled. The diagnosis was made on the basis of a history of acute or subacute knee trauma, local pain, tenderness, cutaneous injury, negative conventional radiography, and positive magnetic resonance imaging (MRI). Because of the impracticability of histological verification of individual OF, MRI was utilized as a gold standard of diagnosis and classification. All patients had (99m)Tc-HDP bone scanning and supplementary GCPBS. GCPBS signs were correlated and compared with those of MRI. The efficacy of gamma correction of ordinary parallel collimator and pinhole collimator scans were collated. Gamma correction pinhole bone scan depicted the signs characteristic of six different types of OF. They were well defined stuffed globular tracer uptake in geographic I fractures (n = 9), block-like uptake in geographic II fractures (n = 7), simple or branching linear uptake in linear cancellous fractures (n = 4), compression in impacted fractures (n = 2), stippled-serpentine uptake in reticular fractures (n = 11), and irregular subcortical uptake in osteochondral fractures (n = 3). All fractures were equally well or more distinctly depicted on GCPBS than on MRI except geographic II fracture, the details of which were not appreciated on GCPBS. Parallel collimator scan also yielded to gamma correction, but the results were inferior to those of the pinhole scan. Gamma correction pinhole bone scan can depict the specific diagnostic signs in six different types of knee occult fractures. The specific diagnostic capability along with the lower cost and wider global availability of bone scanning would make GCPBS an effective alternative.

Sex-related differences of bone properties of pelvic limb and bone metabolism indices in 14-month-old ostriches (Struthio camelus).

PubMed

Krupski, W; Tatara, M R; Charuta, A; Brodzki, A; Szpetnar, M; Jóźwik, A; Strzałkowska, N; Poławska, E; Łuszczewska-Sierakowska, I

2018-06-01

1. Sex-related differences of long pelvic limb bones and serum bone metabolism indices were evaluated in 14-month-old female (N = 7) and male (N = 7) ostriches of similar body weights. 2. Densitometric parameters of femur, tibia and tarsometatarsus were determined using quantitative computed tomography (volumetric bone mineral density, calcium hydroxyapatite density and mean volumetric bone mineral density) and dual energy X-ray absorptiometry (bone mineral density and bone mineral content) methods. Geometrical parameters such as cortical bone area, cross-sectional area, second moment of inertia, mean relative wall thickness and cortical index were determined in the midshaft of bones. Mechanical properties of bones (maximum elastic strength and ultimate strength) were evaluated using three-point bending test. Serum concentrations of free amino acids, osteocalcin, N-terminal propeptide of type I procollagen, C-terminal telopeptides of type II collagen and total antioxidative capacity were also determined. 3. Bone weight and relative bone weight of all bones were significantly higher in males than in females. Significantly lower values of trabecular bone mineral density and calcium hydroxyapatite density were found in the trabecular bone of tibia in males. The highest number of the sex-related differences was observed in the tarsometatarsus where bone length, bone mineral content, cortical bone area, cross-sectional area and ultimate strength were higher in males. Serum concentrations of taurine, hydroxyproline, valine and isoleucine were significantly higher in males. 4. Higher loading of the tarsometatarsus in comparison to femur and tibia may be an important factor interacting with sex hormones in regulation of bone formation and mineralisation processes. Sex-related differences of bone properties were associated with increased serum concentration of selected amino acids in males.

Role of clinician's experience and implant design on implant stability. An ex vivo study in artificial soft bones.

PubMed

Romanos, Georgios E; Basha-Hijazi, Abdulaziz; Gupta, Bhumija; Ren, Yan-Fang; Malmstrom, Hans

2014-04-01

Clinical experience in implant placement is important in order to prevent implant failures. However, the implant design affects the primary implant stability (PS) especially in poor quality bones. Therefore, the aim of this study was to compare the effect of clinician surgical experience on PS, when placing different type of implant designs. A total of 180 implants (90 parallel walled-P and 90 tapered-T) were placed in freshly slaughtered cow ribs. Bone quality was evaluated by two examiners during surgery and considered as 'type IV' bone. Implants (ø 5 mm, length: 15 mm, Osseotite, BIOMET 3i, Palm Beach Gardens, FL, USA) were placed by three different clinicians (master/I, good/II, non-experienced/III, under direct supervision of a manufacturer representative; 30 implants/group). An independent observer assessed the accuracy of placement by resonance frequency analysis (RFA) with implant stability quotient (ISQ) values. Two-way analysis of variance (ANOVA) and Tukey's post hoc test were used to detect the surgical experience of the clinicians and their interaction and effects of implant design on the PS. All implants were mechanically stable. The mean ISQ values were: 49.57(± 18.49) for the P-implants and 67.07(± 8.79) for the T-implants. The two-way ANOVA showed significant effects of implant design (p < .0001), clinician (p < .0001), and their interaction (p < .0001). The Tukey's multiple comparison test showed significant differences in RFA for the clinician group I/II (p = .015) and highly significant (p < .0001) between I/III and II/III. The P-implants presented (for I, II, and III) mean ISQ values 31.25/49.18/68.17 and the T-implants showed higher ISQ values, 70.15/62.08/68.98, respectively. Clinicians I and II did not show extreme differences for T-implants (p = .016). In contrast, clinician III achieved high ISQ values using P- and T-implants following the exact surgical protocol based on the manufacturer guidelines. T-implants provided high stability for experienced clinicians compared with P-implants. T-implants achieved greater PS than the P-implants. All clinicians consistently achieved PS; however, experienced clinicians achieved higher ISQ values with T-implants in poor quality bone. © 2012 Wiley Periodicals, Inc.

Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis.

PubMed

Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

2017-05-23

The local and systemic renin angiotensin system (RAS) influences the skeletal system micro-structure and metabolism. Studies suggested angiotensin 1-7 (Ang(1-7)) as the beneficial RAS molecule via Mas receptor activation. This study examines the function of Ang(1-7) in bone micro-architecture and metabolism in an ovariectomized (OVX) rodent model of osteoporosis. OVX rats showed structural and bone metabolic degeneration in parallel with suppressed expressions of the angiotensin converting enzyme-2 (ACE-2)/Ang(1-7)/Mas components. The infusion of Ang(1-7) markedly alleviated the altered bone metabolism and significantly enhanced both trabecular (metaphyseal) and cortical (metaphyseal-diaphyseal) morphometry. Urinary and bones minerals were also improved in OVX rats by Ang(1-7). The infusion of the heptapeptide enhanced ACE-2/Mas receptor expressions, while down-regulated AngII, ACE, and AngII type-1 receptor (AT1R) in OVX animals. Moreover, Ang(1-7) markedly improved osteoprotegerin (OPG) and lowered receptor activator NF-κB ligand (RANKL) expressions. The defensive properties of Ang(1-7) on bone metabolism, structure and minerals were considerably eradicated after blockage of Mas receptor with A-779. Ang(1-7)-induced up-regulated ACE-2/Ang(1-7)/Mas cascade and OPG expressions were abolished and the expressions of ACE/AngII/AT1R and RANKL were provoked by A-779. These findings shows for the first time the novel valuable therapeutic role of Ang(1-7) on bone health and metabolism through the ACE-2/Mas cascade.

Substitutions of aspartic acid for glycine-220 and of arginine for glycine-664 in the triple helix of the pro alpha 1(I) chain of type I procollagen produce lethal osteogenesis imperfecta and disrupt the ability of collagen fibrils to incorporate crystalline hydroxyapatite.

PubMed Central

Culbert, A A; Lowe, M P; Atkinson, M; Byers, P H; Wallis, G A; Kadler, K E

1995-01-01

We identified two infants with lethal (type II) osteogenesis imperfecta (OI) who were heterozygous for mutations in the COL1A1 gene that resulted in substitutions of aspartic acid for glycine at position 220 and arginine for glycine at position 664 in the product of one COL1A1 allele in each individual. In normal age- and site-matched bone, approximately 70% (by number) of the collagen fibrils were encrusted with plate-like crystallites of hydroxyapatite. In contrast, approximately 5% (by number) of the collagen fibrils in the probands' bone contained crystallites. In contrast with normal bone, the c-axes of hydroxyapatite crystallites were sometimes poorly aligned with the long axis of fibrils obtained from OI bone. Chemical analysis showed that the OI samples contained normal amounts of calcium. The probands' bone samples contained type I collagen, overmodified type I collagen and elevated levels of type III and V collagens. On the basis of biochemical and morphological data, the fibrils in the OI samples were co-polymers of normal and mutant collagen. The results are consistent with a model of fibril mineralization in which the presence of abnormal type I collagen prevents normal collagen in the same fibril from incorporating hydroxyapatite crystallites. Images Figure 1 Figure 2 Figure 3 PMID:7487936

Calcimimetic and Calcilytic Drugs: Feats, Flops, and Futures.

PubMed

Nemeth, E F; Goodman, W G

2016-04-01

The actions of extracellular Ca(2+) in regulating parathyroid gland and kidney functions are mediated by the extracellular calcium receptor (CaR), a G protein-coupled receptor. The CaR is one of the essential molecules maintaining systemic Ca(2+) homeostasis and is a molecular target for drugs useful in treating bone and mineral disorders. Ligands that activate the CaR are termed calcimimetics and are classified as either agonists (type I) or positive allosteric modulators (type II); calcimimetics inhibit the secretion of parathyroid hormone (PTH). Cinacalcet is a type II calcimimetic that is used to treat secondary hyperparathyroidism in patients receiving dialysis and to treat hypercalcemia in some forms of primary hyperparathyroidism. The use of cinacalcet among patients with secondary hyperparathyroidism who are managed with dialysis effectively lowers circulating PTH levels, reduces serum phosphorus and FGF23 concentrations, improves bone histopathology, and may diminish skeletal fracture rates and the need for parathyroidectomy. A second generation type II calcimimetic (AMG 416) is currently under regulatory review. Calcilytics are CaR antagonists that stimulate the secretion of PTH. Several calcilytic compounds have been evaluated as orally active anabolic therapies for postmenopausal osteoporosis but clinical development of all of them has been abandoned because they lacked clinical efficacy. Calcilytics might be repurposed for new indications like autosomal dominant hypocalcemia or other disorders beyond those involving systemic Ca(2+) homeostasis.

Differential response of bone and kidney to ACEI in db/db mice: A potential effect of captopril on accelerating bone loss.

PubMed

Zhang, Yan; Li, Xiao-Li; Sha, Nan-Nan; Shu, Bing; Zhao, Yong-Jian; Wang, Xin-Luan; Xiao, Hui-Hui; Shi, Qi; Wong, Man-Sau; Wang, Yong-Jun

2017-04-01

The components of renin-angiotensin system (RAS) are expressed in the kidney and bone. Kidney disease and bone injury are common complications associated with diabetes. This study aimed to investigate the effects of an angiotensin-converting enzyme inhibitor, captopril, on the kidney and bone of db/db mice. The db/db mice were orally administered by gavage with captopril for 8weeks with db/+ mice as the non-diabetic control. Serum and urine biochemistries were determined by standard colorimetric methods or ELISA. Histological measurements were performed on the kidney by periodic acid-schiff staining and on the tibial proximal metaphysis by safranin O and masson-trichrome staining. Trabecular bone mass and bone quality were analyzed by microcomputed tomography. Quantitative polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. Captopril significantly improved albuminuria and glomerulosclerosis in db/db mice, and these effects might be attributed to the down-regulation of angiotensin II expression and the expression of its down-stream profibrotic factors in the kidney, like connective tissue growth factor and vascular endothelial growth factor. Urinary excretion of calcium and phosphorus markedly increased in db/db mice in response to captopril. Treatment with captopril induced a decrease in bone mineral density and deterioration of trabecular bone at proximal metaphysis of tibia in db/db mice, as shown in the histological and reconstructed 3-dimensional images. Even though captopril effectively reversed the diabetes-induced changes in calcium-binding protein 28-k and vitamin D receptor expression in the kidney as well as the expression of RAS components and bradykinin receptor-2 in bone tissue, treatment with captopril increased the osteoclast-covered bone surface, reduced the osteoblast-covered bone surface, down-regulated the expression of type 1 collagen and transcription factor runt-related transcription factor 2 (markers for osteoblastic functions), and up-regulated the expression of carbonic anhydrase II (marker for bone resorption). Captopril exerted therapeutic effects on renal injuries associated with type 2 diabetes but worsened the deteriorations of trabecular bone in db/db mice; the latter of which was at least in part due to the stimulation of osteoclastogenesis and the suppression of osteogenesis by captopril. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment of Class II malocclusion with mandibular skeletal anchorage.

PubMed

Cakir, Ezgi; Malkoç, Siddik; Kirtay, Mustafa

2017-06-01

The aim of this case report was to present the dentofacial changes obtained with bone anchorage in a Class II patient with moderate to severe crowding. A boy, aged 14.5 years, with a dolichofacial type, convex profile, and skeletal and dental Class II relationships was examined. After evaluation, functional treatment with bone anchorage and 4 first premolar extractions was decided as the treatment approach. Miniplates were placed on the buccal shelves of the mandibular third molars. The hook of the anchor was revealed from the first molar level. After surgery, the 4 first premolars were extracted to retract the protrusive mandibular incisors. The maxillary and mandibular first molars were banded, and a lip bumper was inserted to apply elastics and to help distalize the maxillary first molars. Orthodontic forces of 300 to 500 g were applied immediately after placement, originating from the miniscrews to the hooks of the appliance to advance the mandible. After 20 months of treatment, the patient had a dental and skeletal Class I relationship, the mandible was advanced, the maxilla was restrained, and overjet was decreased. The combination of a bone anchor, Class II elastics, and an inner bow is a promising alternative to functional treatment, along with extractions, in Class II patients. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Weak bones in diabetes mellitus - an update on pharmaceutical treatment options.

PubMed

Lin, Daphne P L; Dass, Crispin R

2018-01-01

Diabetes mellitus is often associated with a number of complications such as nephropathy, neuropathy, retinopathy and foot ulcers. However, weak bone is a diabetic complication that is often overlooked. Although the exact mechanism for weak bones within diabetes mellitus is unclear, studies have shown that the mechanism does differ in both type I (T1DM) and type II diabetes (T2DM). This review, however, investigates the application of mesenchymal stem cells, recombinant human bone morphogenetic protein-2, teriparatide, insulin administration and the effectiveness of a peroxisome proliferator-activated receptor-ϒ modulator, netoglitazone in the context of diabetic weak bones. In T1DM, weak bones may be the result of defective osteoblast activity, the absence of insulin's anabolic effects on bone, the deregulation of the bone-pancreas negative feedback loop and advanced glycation end product (AGE) aggregation within the bone matrix as a result of hyperglycaemia. Interestingly, T2DM patients placed on insulin administration, thiazolidinediones, SGLT2 inhibitors and sulfonylureas have an associated increased fracture risk. T2DM patients are also observed to have high sclerostin levels that impair osteoblast gene transcription, AGE aggregation within bone, which compromises bone strength and a decrease in esRAGE concentration resulting in a negative association with vertebral fractures. Effective treatment options for weak bones in the context of diabetes are currently lacking. There is certainly scope for discovery and development of novel agents that could alleviate this complication in diabetes patients. © 2017 Royal Pharmaceutical Society.

Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model.

PubMed

Bell, Angela D; Hurtig, Mark B; Quenneville, Eric; Rivard, Georges-Étienne; Hoemann, Caroline D

2017-10-01

Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan-NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro-computed tomography after 1 day ( n = 1) and 6 months ( n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage.

Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model

PubMed Central

Bell, Angela D.; Hurtig, Mark B.; Quenneville, Eric; Rivard, Georges-Étienne; Hoemann, Caroline D.

2016-01-01

Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan–NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro–computed tomography after 1 day (n = 1) and 6 months (n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage. PMID:28934884

Protein kinase D1 is essential for bone acquisition during pubertal growth.

PubMed

Ford, Jeffery J; Yeh, Lee-Chuan C; Schmidgal, Eric C; Thompson, Jason F; Adamo, Martin L; Lee, John C

2013-11-01

Bone formation and maintenance represents the summation of the balance of local and endocrine hormonal stimuli within a complex organ. Protein kinase D (PKD) is a member of the Ca(2+)/calmodulin-dependent kinase superfamily of serine/threonine kinases and has been described as the crossroads for the bone morphogenetic protein (BMP)-IGF-I signaling axis, which plays a major role in bone formation. The current study exploits the PKD1-deficient mouse model to examine the role of PKD in vivo in the skeleton. Dual-energy x-ray absorptiometry scan analysis of male and female pubescent mice demonstrated significantly decreased bone mineral density in the whole body and femoral bone compartments of PKD1 (+/-) mice, compared with their wild-type littermates. The body weight, nasal-anal length, and percentage body fat of the mice were not significantly different from their wild-type littermates. Cultured bone marrow stromal cells from PKD1 (+/-) mice demonstrated lower alkaline phosphatase activity in early differentiating osteoblasts and decreased mineralized nodule formation in mature osteoblasts. Quantitative RT-PCR analysis of osteoblast differentiation markers and osteoclast markers exhibited lower levels of expression in PKD1 (+/-) male mice than wild type. In female mice, however, only markers of osteoblast differentiation were reduced. PKD1 (+/-) mice also demonstrated a profound reduction in mRNA expression levels of BMP type II receptor and IGF-I receptor and in BMP-7 responsiveness in vitro. Together these data suggest that in mice, PKD1 action contributes to the regulation of osteoblastogenesis by altering gene expression with gender-specific effects on osteoclastogenesis, subsequently affecting skeletal matrix acquisition during puberty.

Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.

PubMed

Gleitz, Hélène Fe; Liao, Ai Yin; Cook, James R; Rowlston, Samuel F; Forte, Gabriella Ma; D'Souza, Zelpha; O'Leary, Claire; Holley, Rebecca J; Bigger, Brian W

2018-06-08

The pediatric lysosomal storage disorder mucopolysaccharidosis type II is caused by mutations in IDS, resulting in accumulation of heparan and dermatan sulfate, causing severe neurodegeneration, skeletal disease, and cardiorespiratory disease. Most patients manifest with cognitive symptoms, which cannot be treated with enzyme replacement therapy, as native IDS does not cross the blood-brain barrier. We tested a brain-targeted hematopoietic stem cell gene therapy approach using lentiviral IDS fused to ApoEII (IDS.ApoEII) compared to a lentivirus expressing normal IDS or a normal bone marrow transplant. In mucopolysaccharidosis II mice, all treatments corrected peripheral disease, but only IDS.ApoEII mediated complete normalization of brain pathology and behavior, providing significantly enhanced correction compared to IDS. A normal bone marrow transplant achieved no brain correction. Whilst corrected macrophages traffic to the brain, secreting IDS/IDS.ApoEII enzyme for cross-correction, IDS.ApoEII was additionally more active in plasma and was taken up and transcytosed across brain endothelia significantly better than IDS via both heparan sulfate/ApoE-dependent receptors and mannose-6-phosphate receptors. Brain-targeted hematopoietic stem cell gene therapy provides a promising therapy for MPS II patients. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

[Influencing factors for trauma-induced tibial infection in underground coal mine].

PubMed

Meng, W Z; Guo, Y J; Liu, Z K; Li, Y F; Wang, G Z

2016-07-20

Objective: To investigate the influencing factors for trauma-induced tibial infection in underground coal mine. Methods: A retrospective analysis was performed for the clinical data of 1 090 patients with tibial fracture complicated by bone infection who were injured in underground coal mine and admitted to our hospital from January 1995 to August 2015, including the type of trauma, injured parts, severity, and treatment outcome. The association between risk factors and infection was analyzed. Results: Among the 1 090 patients, 357 had the clinical manifestations of acute and chronic bone infection, 219 had red and swollen legs with heat pain, and 138 experienced skin necrosis, rupture, and discharge of pus. The incidence rates of tibial infection from 1995 to 2001, from 2002 to 2008, and from 2009 to 2015 were 31%, 26.9%, and 20.2%, respectively. The incidence rate of bone infection in the proximal segment of the tibia was significantly higher than that in the middle and distal segments (42.1% vs 18.9%/27.1%, P <0.01) . As for patients with different types of trauma (Gustilo typing) , the patients with type III fracture had a significantly higher incidence rate of bone infection than those with type I/II infection (52.8% vs 21.8%/24.6%, P <0.01) . The incidence rates of bone infection after bone traction, internal fixation with steel plates, fixation with external fixator, and fixation with intramedullary nail were 20.7%, 43.5%, 21.4%, and 26.1%, respectively, suggesting that internal fixation with steel plates had a significantly higher incidence rate of bone infection than other fixation methods ( P <0.01) . The multivariate logistic regression analysis showed that the position of tibial fracture and type of fracture were independent risk factors for bone infection. Conclusion: There is a high incidence rate of trauma-induced tibial infection in workers in underground coal mine. The position of tibial fracture and type of fracture are independent risk factors for bone infection. Vacuum sealing drainage and Ilizarov technique can achieve a satisfactory therapeutic effect.

Salter-Harris type II metacarpal and metatarsal fracture in three foals. Treatment by minimally-invasive lag screw osteosynthesis combined with external coaptation.

PubMed

Klopfenstein Bregger, Micaël D; Fürst, Anton E; Kircher, Patrick R; Kluge, Katharina; Kummer, Martin

2016-05-18

To describe minimally-invasive lag screw osteosynthesis combined with external coaptation for the treatment of Salter-Harris type II third metacarpal and third metatarsal bone fractures. Three foals aged two weeks to four months with a Salter-Harris type II third metacarpal or third metatarsal fracture. Surgery was carried out under general anaesthesia in lateral recumbency. After fracture reduction, the metaphyseal fragment was stabilized with two cortical screws placed in lag fashion under fluoroscopic control. A cast was applied for at least two weeks. All foals had a good outcome with complete fracture healing and return to complete soundness without any angular limb deformity. All foals had moderate transient digital hyperextension after cast removal. Internal fixation of Salter-Harris type II third metacarpal or third metatarsal fractures with two cortical screws in lag fashion, combined with external coaptation provided good stabilization and preserved the longitudinal growth potential of the injured physis.

Morphology of bone particles after harvesting with 4 different devices.

PubMed

Papadimitriou, Dimitrios E V; Schmidt, Erich C; Caton, Jack G; Romanos, Georgios E

2013-04-01

Autogenous bone is routinely used for regeneration of osseous defects around teeth and implants, and different instruments are available for bone harvesting. The purpose of this study was to describe the morphology of bone particles after harvesting with 4 different instruments. Bone particles were harvested from fresh cow ribs with 2 different types of back action chisels, a safescraper and a sonic device. The samples were examined morphologically using light microscopy and scanning electron microscopy. The bone particles after the back action chisel I had an appearance similar to "pencil shavings." With the back action chisel II, they were like thin paper with an "accordion bellows" appearance. After removal with the safescraper, they had an irregular shape (with an irregular surface) resembling "crushed stone." Finally, the appearance of the bone particles obtained with the sonic device was homogenous, condensed and continuous, and had a "seaweed" appearance. Harvesting of bone particles with 4 different devices produce distinctly difference sizes and shapes, which may influence the results of grafting procedures.

Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis

NASA Technical Reports Server (NTRS)

Conover, Cheryl A.; Johnstone, Edward W.; Turner, Russell T.; Evans, Glenda L.; John Ballard, F. John; Doran, Patrick M.; Khosla, Sundeep

2002-01-01

Elevated serum levels of insulin-like growth factor binding protein-2 (IGFBP-2) and a precursor form of IGF-II are associated with marked increases in bone formation and skeletal mass in patients with hepatitis C-associated osteosclerosis. In vitro studies indicate that IGF-II in complex with IGFBP-2 has high affinity for bone matrix and is able to stimulate osteoblast proliferation. The purpose of this study was to determine the ability of the IGF-II/IGFBP-2 complex to increase bone mass in vivo. Osteopenia of the femur was induced by unilateral sciatic neurectomy in rats. At the time of surgery, 14-day osmotic minipumps containing vehicle or 2 microg IGF-II+9 microg IGFBP-2/100g body weight/day were implanted subcutaneously in the neck. Bone mineral density (BMD) measurements were taken the day of surgery and 14 days later using a PIXImus small animal densitometer. Neurectomy of the right hindlimb resulted in a 9% decrease in right femur BMD (P<0.05 vs. baseline). This loss in BMD was completely prevented by treatment with IGF-II/IGFBP-2. On the control limb, there was no loss of BMD over the 14 days and IGF-II/IGFBP-2 treatment resulted in a 9% increase in left femur BMD (P<0.05). Bone histomorphometry indicated increases in endocortical and cancellous bone formation rates and in trabecular thickness. These results demonstrate that short-term administration of the IGF-II/IGFBP-2 complex can prevent loss of BMD associated with disuse osteoporosis and stimulate bone formation in adult rats. Furthermore, they provide proof of concept for a novel anabolic approach to increasing bone mass in humans with osteoporosis.

Temperature and time variations during osteotomies performed with different piezosurgical devices: an in vitro study.

PubMed

Delgado-Ruiz, R A; Sacks, D; Palermo, A; Calvo-Guirado, J L; Perez-Albacete, C; Romanos, G E

2016-09-01

The aim of this experimental in vitro study was to evaluate the effects of the piezoelectric device in temperature and time variations in standardized osteotomies performed with similar tip inserts in bovine bone blocks. Two different piezosurgical devices were used the OE-F15(®) (Osada Inc., Los Angeles, California, USA) and the Surgybone(®) (Silfradent Inc., Sofia, Forli Cesena, Italy). Serrated inserts with similar geometry were coupled with each device (ST94 insert/test A and P0700 insert/test B). Osteotomies 10 mm long and 3 mm deep were performed in bone blocks resembling type II (dense) and type IV (soft) bone densities with and without irrigation. Thermal changes and time variations were recorded. The effects of bone density, irrigation, and device on temperature changes and time necessary to accomplish the osteotomies were analyzed. Thermal analysis showed significant higher temperatures during piezosurgery osteotomies in hard bone without irrigation (P < 0.05). The type of piezosurgical device did not influence thermal variations (P > 0.05). Time analysis showed that the mean time values necessary to perform osteotomies were shorter in soft bone than in dense bone (P < 0.05). Within the limitations of this in vitro study, it may be concluded that the temperature increases more in piezosurgery osteotomies in dense bone without irrigation; the time to perform the osteotomy with piezosurgery is shorter in soft bone compared to hard bone; and the piezosurgical device have a minimal influence in the temperature and time variations when a similar tip design is used during piezosurgery osteotomies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An Immunohistochemical Study of Matrix Proteins in the Craniofacial Cartilage in Midterm Human Fetuses

PubMed Central

Shibata, S.; Sakamoto, Y.; Baba, O.; Qin, C.; Murakami, G.; Cho, B.H.

2013-01-01

Immunohistochemical localization of collagen types I, II, and X, aggrecan, versican, dentin matrix protein (DMP)-1, martix extracellular phosphoprotein (MEPE) were performed for Meckel’s cartilage, cranial base cartilage, and mandibular condylar cartilage in human midterm fetuses; staining patterns within the condylar cartilage were compared to those within other cartilaginous structures. Mandibular condylar cartilage contained aggrecan; it also had more type I collagen and a thicker hypertrophic cell layer than the other two types of cartilage; these three characteristics are similar to those of the secondary cartilage of rodents. MEPE immunoreactivity was first evident in the cartilage matrix of all types of cartilage in the human fetuses and in Meckel’s cartilage of mice and rats. MEPE immunoreactivity was enhanced in the deep layer of the hypertrophic cell layer and in the cartilaginous core of the bone trabeculae in the primary spongiosa. These results indicated that MEPE is a component of cartilage matrix and may be involved in cartilage mineralization. DMP-1 immunoreactivity first became evident in human bone lacunae walls and canaliculi; this pattern of expression was comparable to the pattern seen in rodents. In addition, chondroid bone was evident in the mandibular (glenoid) fossa of the temporal bone, and it had aggrecan, collagen types I and X, MEPE, and DMP-1 immunoreactivity; these findings indicated that chondroid bone in this region has phenotypic expression indicative of both hypertrophic chondrocytes and osteocytes. PMID:24441192

Influence of bone morphogenetic protein and proportion of hydroxyapatite on new bone formation in biphasic calcium phosphate graft: two pilot studies in animal bony defect model.

PubMed

Yun, Pil-Young; Kim, Young-Kyun; Jeong, Kyung-In; Park, Ju-Cheol; Choi, Yeon-Jo

2014-12-01

The purpose of these two pilot studies using animal bony defect models was to evaluate the influence of bone morphogenetic protein (BMP) and proportion of hydroxyapatite (HA)/beta-tricalcium phosphate (β-TCP) in biphasic calcium phosphate (BCP) graft on new bone formation. In this study, four kinds of synthetic osteoconductive bone materials known for bone growth scaffold, OSTEON™II(HA:β-TCP 30:70), OSTEON™III (HA:β-TCP 20:80), OSTEON™II Collagen, and OSTEON™III Collagen, were prepared as BCP graft materials. In pilot study 1, three BCP materials (OSTEON™II, OSTEON™III, and OSTEON™II Collagen) were grafted in rabbit calvarial defects after impregnating in rhBMP-2. OSTEON™II without the rhBMP-2 impregnation was included in the study as the control. The amount of new bone was examined and measured histologically at 2, 4, and 8 weeks. In pilot study 2, four BCP materials (OSTEON™II, OSTEON™III, OSTEON™II Collagen, and OSTEON™III Collagen) were grafted in beagle dog mandibular defects after soaking in the rhBMP-2. The amount of total bone and new bone were measured three-dimensionally using microCT and healing process was examined histologically at 2, 4, and 8 weeks. In pilot study 1, rhBMP-2 impregnated groups showed more new bone formation than the rhBMP-2 free group. In pilot study 2, increased new bone formation was observed in time-dependent manner after graft of BCP and BCP-collagen (OSTEON™II, OSTEON™III, OSTEON™II Collagen, and OSTEON™III Collagen) impregnated with rhBMP-2. Also, BCP with a higher proportion of HA (30% HA) showed more favorable result in new bone formation and space maintenance, especially at the 8 weeks. From the results of the pilot studies, rhBMP-2 played positive roles in new bone formation and BCP could become a scaffold candidate for rhBMP-2 impregnation to induce new bone formation. Moreover, BCP with a higher proportion of HA (30% HA) could be considered more appropriate for rhBMP-2 carrier. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

An {alpha}1(II) Gly{sup 913} to cys substitution prevents the matrix incorporation of type II collagen which is replaced with type I and III collagens in cartilage from a patient with hypochondrogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mundlos, S.; Chan, D.; Bateman, J.F.

1996-05-03

A heterozygous mutation in the COL2A1 gene was identified in a patient with hypochondrogenesis. The mutation was a single nucleotide transition of G3285T that resulted in an amino acid substitution of Cys for Gly{sup 913} in the {alpha}1(II) chain of type II collagen. This amino acid change disrupted the obligatory Gly-X-Y triplet motif required for the normal formation of a stable collagen triple helix and prevented the deposition of type II collagen into the proposita`s cartilage, which contained predominantly type I and III collagens and minor amounts of type XI collagen. Biosynthetic analysis of collagens produced and secreted by themore » patient`s chondrocytes cultured in alginate beads was consistent with the in vivo matrix composition, demonstrating that the main products were type I and III collagens, along with type XI collagen. The synthesis of the cartilage-specific type XI collagen at similar levels to controls indicated that the isolated cartilage cells had re-differentiated to the chondrocyte phenotype. The chondrocytes also produced small amounts of type II collagen, but this was post-translationally overmodified and not secreted. These data further delineate the biochemical and phenotypic consequences of mutations in the COL2A1 gene and suggest that cartilage formation and bone development can take place in the absence of type II collagen. 23 refs., 5 figs.« less

Microcontact printing of BMP-2 and its effect on human chondrocytes behavior

NASA Astrophysics Data System (ADS)

Pan, Chang-Jiang; Nie, Yu-Dong

2010-01-01

The present study is to investigate human chondrocytes behavior on microcontact printed bone morphogenetic protein-2 (BMP-2) lines on polystyrene (PS) surface. It was found that the cells aligned with BMP lines and expressed type II and VI collagen. The chondrocytes in vitro cultured on BMP lines were elongated, which resulted in altered cell morphology. Taking all these results into consideration, BMP-2 lines enhance cell adhesion, restrict spreading, and increase type II and VI collagen expression. The results represented in this study may be an approach to the problem of engineering reparative cartilage in vitro.

Alteration of the bone tissue material properties in type 1 diabetes mellitus: A Fourier transform infrared microspectroscopy study.

PubMed

Mieczkowska, Aleksandra; Mansur, Sity Aishah; Irwin, Nigel; Flatt, Peter R; Chappard, Daniel; Mabilleau, Guillaume

2015-07-01

Type 1 diabetes mellitus (T1DM) is a severe disorder characterized by hyperglycemia and hypoinsulinemia. A higher occurrence of bone fractures has been reported in T1DM, and although bone mineral density is reduced in this disorder, it is also thought that bone quality may be altered in this chronic pathology. Vibrational microscopies such as Fourier transform infrared microspectroscopy (FTIRM) represent an interesting approach to study bone quality as they allow investigation of the collagen and mineral compartment of the extracellular matrix in a specific bone location. However, as spectral feature arising from the mineral may overlap with those of the organic component, the demineralization of bone sections should be performed for a full investigation of the organic matrix. The aims of the present study were to (i) develop a new approach, based on the demineralization of thin bone tissue section to allow a better characterization of the bone organic component by FTIRM, (ii) to validate collagen glycation and collagen integrity in bone tissue and (iii) to better understand what alterations of tissue material properties in newly forming bone occur in T1DM. The streptozotocin-injected mouse (150 mg/kg body weight, injected at 8 weeks old) was used as T1DM model. Animals were randomly allocated to control (n = 8) or diabetic (n = 10) groups and were sacrificed 4 weeks post-STZ injection. Bones were collected at necropsy, embedded in polymethylmethacrylate and sectioned prior to examination by FTIRM. FTIRM collagen parameters were collagen maturity (area ratio between 1660 and 1690 cm(-1) subbands), collagen glycation (area ratio between the 1032 cm(-1) subband and amide I) and collagen integrity (area ratio between the 1338 cm(-1) subband and amide II). No significant differences in the mineral compartment of the bone matrix could be observed between controls and STZ-injected animals. On the other hand, as compared with controls, STZ-injected animals presented with significant higher value for collagen maturity (17%, p = 0.0048) and collagen glycation (99%, p = 0.0121), while collagen integrity was significantly lower by 170% (p = 0.0121). This study demonstrated the profound effect of early T1DM on the organic compartment of the bone matrix in newly forming bone. Further studies in humans are required to ascertain whether T1DM also lead to similar effect on the quality of the bone matrix. Copyright © 2015 Elsevier Inc. All rights reserved.

Phenotypic expressions of a Gly154Arg mutation in type II collagen in two unrelated patients with spondyloepimetaphyseal dysplasia (SEMD)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaitila, I.; Marttinen, E.; Koerkkoe, J.

1996-05-03

Type II collagenopathies consist of chondrodysplasia ranging from lethal to mild in severity. A large number of mutations has been found in the COL2A1 gene. Glycine substitutions have been the most common types of mutation. Genotype-phenotype correlations in type II collagenopathies have not been established, partly because of insufficient clinical and radiographic description of the patients. We found a glycine-to-arginine substitution at position 154 in type II collagen in two unrelated isolated propositi with spondyloepimetaphyseal dysplasia and provide a comparative clinical and radiographic analysis from birth to young adulthood for this condition. The clinical phenotype was disproportionate short stature withmore » varus/valgus deformities of the lower limbs requiring corrective osteotomies, and lumbar lordosis. The skeletal radiographs showed an evolution from short tubular bones, delayed epiphyseal development, and mild vertebral involvement to severe metaphyseal dysplasia with dappling irregularities, and hip {open_quotes}dysplasia.{close_quotes} The metaphyseal abnormalities disappeared by adulthood. 27 refs., 11 figs., 1 tab.« less

Current and emerging treatments for the management of osteogenesis imperfecta

PubMed Central

Monti, Elena; Mottes, Monica; Fraschini, Paolo; Brunelli, PierCarlo; Forlino, Antonella; Venturi, Giacomo; Doro, Francesco; Perlini, Silvia; Cavarzere, Paolo; Antoniazzi, Franco

2010-01-01

Osteogenesis imperfecta (OI) is the most common bone genetic disorder and it is characterized by bone brittleness and various degrees of growth disorder. Clinical severity varies widely; nowadays eight types are distinguished and two new forms have been recently described although not yet classified. The approach to such a variable and heterogeneous disease should be global and therefore multidisciplinary. For simplicity, the objectives of treatment can be reduced to three typical situations: the lethal perinatal form (type II), in which the problem is survival at birth; the severe and moderate forms (types III–IX), in which the objective is ‘autonomy’; and the mild form (type I), in which the aim is to reach ‘normal life’. Three types of treatment are available: non-surgical management (physical therapy, rehabilitation, bracing and splinting), surgical management (intramedullary rod positioning, spinal and basilar impression surgery) and medical-pharmacological management (drugs to increase the strength of bone and decrease the number of fractures as bisphosphonates or growth hormone, depending on the type of OI). Suggestions and guidelines for a therapeutic approach are indicated and updated with the most recent findings in OI diagnosis and treatment. PMID:20856683

Single-screw Fixation of Adolescent Salter-II Proximal Humeral Fractures: Biomechanical Analysis of the "One Pass Door Lock" Technique.

PubMed

Miller, Mark Carl; Redman, Christopher N; Mistovich, R Justin; Muriuki, Muturi; Sangimino, Mark J

2017-09-01

Pin fixation of Salter-II proximal humeral fractures in adolescents approaching skeletal maturity has potential complications that can be avoided with single-screw fixation. However, the strength of screw fixation relative to parallel and diverging pin fixation is unknown. To compare the biomechanical fixation strength between these fixation modalities, we used synthetic composite humeri, and then compared these results in composite bone with cadaveric humeri specimens. Parallel pinning, divergent pinning, and single-screw fixation repairs were performed on synthetic composite humeri with simulated fractures. Six specimens of each type were tested in axial loading and other 6 were tested in torsion. Five pair of cadaveric humeri were tested with diverging pins and single screws for comparison. Single-screw fixation was statistically stronger than pin fixation in axial and torsional loading in both composite and actual bone. There was no statistical difference between composite and cadaveric bone specimens. Single-screw fixation can offer greater stability to adolescent Salter-II fractures than traditional pinning. Single-screw fixation should be considered as a viable alternative to percutaneous pin fixation in transitional patients with little expected remaining growth.

In vivo outcomes of tissue-engineered osteochondral grafts.

PubMed

Bal, B Sonny; Rahaman, Mohamed N; Jayabalan, Prakash; Kuroki, Keiichi; Cockrell, Mary K; Yao, Jian Q; Cook, James L

2010-04-01

Tissue-engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue-engineered osteochondral grafts synthesized by bonding mesenchymal stem cell-loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow-derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue-engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth-implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline-like tissue at the graft surface, and expressing type II collagen in the articular cartilage.

"Ocular moyamoya" syndrome in a patient with features of microcephalic osteodysplastic primordial dwarfism type II.

PubMed

Bang, Genie M; Kirmani, Salman; Patton, Alice; Pulido, Jose S; Brodsky, Michael C

2013-02-01

Primordial dwarfism refers to severely impaired growth beginning early in fetal life. There are many genetic causes of primordial dwarfism, including disorders classified as microcephalic osteodysplastic primordial dwarfism. Microcephalic osteodysplastic primordial dwarfism type II is an autosomal-recessive disease characterized by small stature, bone and dental anomalies, and characteristic facies. Affected patients have a high risk of stroke secondary to progressive cerebral vascular anomalies, which often are classified as moyamoya disease. We present the case of a boy with features suggestive of MOPD II with unilateral moyamoya cerebrovascular changes and correlative moyamoya collaterals involving the iris of the ipsilateral eye. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Genotyping of samples from German patients with ocular, cerebral and systemic toxoplasmosis reveals a predominance of Toxoplasma gondii type II.

PubMed

Herrmann, Daland C; Maksimov, Pavlo; Hotop, Andrea; Groß, Uwe; Däubener, Walter; Liesenfeld, Oliver; Pleyer, Uwe; Conraths, Franz J; Schares, Gereon

2014-10-01

Toxoplasmosis is an important zoonosis transmitted from animals to humans world-wide. In order to determine Toxoplasma gondii genotypes in individuals living in Germany and to compare findings with those in animals, we analysed nine independent and unlinked genetic markers (nSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) by PCR-RFLP in 83 archived T. gondii-positive DNA samples from patients with ocular toxoplasmosis (n=35), toxoplasmic encephalitis (n=32), systemic toxoplasmosis after bone-marrow transplantation (n=15) and congenital toxoplasmosis (n=1). In 46 of these 83 samples the presence of T. gondii DNA was confirmed by conventional end-point PCR. Among these, 17 T. gondii-positive samples were typed at all nine loci. The majority (15/17, 88.2%) of these samples were of T. gondii type II (i.e., including both, the Apico type II and Apico type I variants). In addition, in one sample a T. gondii type II/type III allele combination and in another sample a T. gondii genotype displaying type III alleles at all markers was observed. In the remaining 11 samples, in which T. gondii could only be partially typed, exclusively type II (n=10) or type III (n=1) alleles were observed. Results of the present study suggest that the majority of patients in Germany are infected with type II T. gondii regardless of the clinical manifestation of toxoplasmosis. This finding is in accord with the predominance of type II T. gondii in oocysts isolated from cats and in tissues of other intermediate hosts in Germany. Copyright © 2014 Elsevier GmbH. All rights reserved.

A novel approach to breast cancer diagnosis via PET imaging of microcalcifications using 18F-NaF

PubMed Central

Wilson, George H.; Gore, John C.; Yankeelov, Thomas E.; Barnes, Stephanie; Peterson, Todd E.; True, Jarrod M.; Shokouhi, Sepideh; McIntyre, J. Oliver.; Sanders, Melinda; Abramson, Vandana; Ngyuen, The-Quyen; Mahadevan-Jansen, Anita; Tantawy, Mohammed N.

2015-01-01

Rationale Current radiological methods for diagnosing breast cancer detect specific morphological features of solid tumors and/or any associated calcium deposits. These deposits originate from an early molecular microcalcification process which consists of two types: type 1 is calcium oxylate (CO) and type II is carbonated calcium hydroxyapetite (HAP). Type I microcalcifications are mainly associated with benign tumors while type II have been shown to be produced, internally, by malignant cells. No current non-invasive in vivo techniques are available for detecting intratumoral microcalcifications. Such a technique would have a significant impact on breast cancer diagnosis and prognosis in preclinical and clinical settings. 18F-NaF PET has been solely used for bone imaging by targeting the bone HAP. In this work, we provide preliminary evidence that 18F-NaF PET imaging can be used to detect breast cancer by targeting the HAP lattice within the tumor microenvironment with high specificity and soft-tissue contrast-to-background ratio, while delineating tumors from inflammation. METHODS Mice were injected with approximately 106 MDA-MB-231 cells subcutaneously and imaged with 18F-NaF PET/CT in a 120 min dynamic sequence when the tumors reached a size of ~250 mm3. Regions-of-interest (ROIs) were drawn around the tumor, muscle, and bone. The concentration of the radiotracer within those ROIs were compared to one another. For comparison to inflammation, rats with inflammatory paws were subjected to 18F-NaF PET imaging. RESULTS Tumor uptake of 18F− was significantly higher (p<0.05) than muscle uptake where the tumor-to-muscle ratio was ~3.5. The presence of type II microcalcification in the MDA-MB-231 cell line was confirmed histologically using alizarin red S and von Kossa staining as well as Raman microspectroscopy. No uptake of 18F− was observed in the rat inflamed tissue. Lack of HAP in the inflamed tissue was verified histologically. CONCLUSIONS This study provides preliminary evidence suggesting that specific targeting of the HAP within the tumor microenvironment with 18F may be able to distinguishing between inflammation and cancer. PMID:24833491

Multivariate linear regression analysis to identify general factors for quantitative predictions of implant stability quotient values

PubMed Central

Huang, Hairong; Xu, Zanzan; Shao, Xianhong; Wismeijer, Daniel; Sun, Ping; Wang, Jingxiao

2017-01-01

Objectives This study identified potential general influencing factors for a mathematical prediction of implant stability quotient (ISQ) values in clinical practice. Methods We collected the ISQ values of 557 implants from 2 different brands (SICace and Osstem) placed by 2 surgeons in 336 patients. Surgeon 1 placed 329 SICace implants, and surgeon 2 placed 113 SICace implants and 115 Osstem implants. ISQ measurements were taken at T1 (immediately after implant placement) and T2 (before dental restoration). A multivariate linear regression model was used to analyze the influence of the following 11 candidate factors for stability prediction: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting, insertion torque, I-stage or II-stage healing pattern, implant diameter, implant length and T1-T2 time interval. Results The need for bone grafting as a predictor significantly influenced ISQ values in all three groups at T1 (weight coefficients ranging from -4 to -5). In contrast, implant diameter consistently influenced the ISQ values in all three groups at T2 (weight coefficients ranging from 3.4 to 4.2). Other factors, such as sex, age, I/II-stage implantation and bone type, did not significantly influence ISQ values at T2, and implant length did not significantly influence ISQ values at T1 or T2. Conclusions These findings provide a rational basis for mathematical models to quantitatively predict the ISQ values of implants in clinical practice. PMID:29084260

Influence of Drilling Speed on Stability of Tapered Dental Implants: An Ex Vivo Experimental Study.

PubMed

Almeida, Karen P; Delgado-Ruiz, Rafael; Carneiro, Leandro G; Leiva, Alberto Bordonaba; Calvo-Guirado, Jose Luis; Gómez-Moreno, Gerardo; Malmström, Hans; Romanos, Georgios E

2016-01-01

The aim of this study was to evaluate whether the drilling speed used during implant site preparation influences primary stability. Eighty tapered designed implants (3.8 × 10 mm) were inserted following osteotomies created in solid rigid polyurethane foam (simulating bone type II) and cellular rigid polyurethane foam (simulating bone type IV). Half were prepared using drilling speeds of 800 rpm (low speed), and the other half were prepared using speeds of 1,500 rpm (high speed). Following insertion, implant primary stability was measured using Periotest and Osstell (resonance frequency analysis [RFA]) devices. Two-way analysis of variance (ANOVA) used for this study found that the drilling speed used to create the osteotomies appeared to have no significant impact on primary stability. The bone quality and not the osteotomy drilling speed seems to influence the implant primary stability.

Optical assessment of bone bioimplants

NASA Astrophysics Data System (ADS)

Timchenko, P. E.; Timchenko, E. V.; Volova, L. T.; Dolgushkin, D. A.; Boltovskaya, V. V.; Frolov, O. O.; Fedorova, Ya. V.

2017-08-01

The results of application of the Raman spectroscopy method for the estimation of alternative sources for the production of bone spongy implants using the "Lioplast" technology, namely, the femoral heads resected in the operation of hip replacement surgery, are presented. It is shown that Raman spectroscopy can be used to estimate the component composition of the surface of bone implants during their processing. Comparing different sources of sponge bone production, no significant differences were found, but there are differences in the ratio of the intensities of the Raman peaks at wave numbers 1555 cm-1 and 1665 cm-1 corresponding to amide II and amide I, and also in the intensity of Raman peaks at wave numbers of 959 cm-1 (PO4 3- (ν1)) and 1068 cm-1 (CO3 2- (ν1) B-type substitution).

Generation of novel bone forming cells (monoosteophils) from the cathelicidin-derived peptide LL-37 treated monocytes.

PubMed

Zhang, Zhifang; Shively, John E

2010-11-15

Bone generation and maintenance involve osteoblasts, osteoclasts, and osteocytes which originate from unique precursors and rely on key growth factors for differentiation. However, an incomplete understanding of bone forming cells during wound healing has led to an unfilled clinical need such as nonunion of bone fractures. Since circulating monocytes are often recruited to sites of injury and may differentiate into various cell types including osteoclasts, we investigated the possibility that circulating monocytes in the context of tissue injury may also contribute to bone repair. In particular, we hypothesized that LL-37 (produced from hCAP-18, cathelicidin), which recruits circulating monocytes during injury, may play a role in bone repair. Treatment of monocytes from blood with LL-37 for 6 days resulted in their differentiation to large adherent cells. Growth of LL-37-differentiated monocytes on osteologic discs reveals bone-like nodule formation by scanning electron microscopy (SEM). In vivo transplantation studies in NOD/SCID mice show that LL-37-differentiated monocytes form bone-like structures similar to endochondral bone formation. Importantly, LL-37-differentiated monocytes are distinct from conventional monocyte-derived osteoclasts, macrophages, and dendritic cells and do not express markers of the mesenchymal stem cells (MSC) lineage, distinguishing them from the conventional precursors of osteoblasts. Furthermore, LL-37 differentiated monocytes express intracellular proteins of both the osteoblast and osteoclast lineage including osteocalcin (OC), osteonectin (ON), bone sialoprotein II (BSP II), osteopontin (OP), RANK, RANKL, MMP-9, tartrate resistant acid phosphatase (TRAP), and cathepsin K (CK). Blood derived monocytes treated with LL-37 can be differentiated into a novel bone forming cell that functions both in vitro and in vivo. We propose the name monoosteophil to indicate their monocyte derived lineage and their bone forming phenotype. These cells may have wide ranging implications in the clinic including repair of broken bones and treatment of osteoporosis.

Horizontal alveolar bone loss: A periodontal orphan

PubMed Central

Jayakumar, A.; Rohini, S.; Naveen, A.; Haritha, A.; Reddy, Krishnanjeneya

2010-01-01

Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician’s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs) (of patients diagnosed with chronic periodontitis and seeking periodontal care), which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm) or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36%) OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2%) teeth, and vertical defects were found only in 264 (7.8%) of the teeth, which was statistically significant (P<.001). Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3%) have addressed vertical bone loss, and 18 (3.7%) have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment modalities for this type of bone loss. This study should be an impetus for greater attention to an otherwise ubiquitous periodontal challenge. PMID:21760673

Management of localized advance loss of periodontal support associated Grade II furcation and intrabony defect in chronic periodontitis patient through amalgamation of platelet-rich fibrin and hydroxyapatite bioactive glass composite granules.

PubMed

Salaria, Sanjeev Kumar; Ghuman, Simrat Kaur; Kumar, Saurabh; Sharma, Garima

2016-01-01

Periodontal disease is infectious, complex, multifactorial, chronic inflammatory disease of supporting periodontal tissues that not only alters the bone morphology but also leads to the reduction in bone height. Different types of bony deformities such as horizontal, vertical, craters, and furcation result from periodontal disease, but vertical and Grade II furcation defects are more amenable to regenerative periodontal therapy. The present case report describes the current concept of periodontal diagnosis and the clinical radiographical efficiency of platelet-rich fibrin and hydroxyapatite bioactive glass composite granules graft combination in the management of localized advance osseous defects with respect to tooth number 36 in chronic periodontitis patient at 1 year postoperatively.

Effects of losartan treatment on the physicochemical properties of diabetic rat bone.

PubMed

Donmez, Baris Ozgur; Unal, Mustafa; Ozdemir, Semir; Ozturk, Nihal; Oguz, Nurettin; Akkus, Ozan

2017-03-01

Inhibitors of the renin-angiotensin system used to treat several diseases have also been shown to be effective on bone tissue, suggesting that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may reduce fracture risk. The present study investigated the effects of losartan on the physicochemical and biomechanical properties of diabetic rat bone. Losartan (5 mg/kg/day) was administered via oral gavage for 12 weeks. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Whole femurs were tested under tension to evaluate the biomechanical properties of bone. The physicochemical properties of bone were analyzed by Fourier transform infrared spectroscopy. Although losartan did not recover decreases in the BMD of diabetic bone, it recovered the physicochemical (mineral and collagen matrix) properties of diabetic rat bone. Furthermore, losartan also recovered ultimate tensile strength of diabetic rat femurs. Losartan, an angiotensin II type 1 receptor blocker, has a therapeutic effect on the physicochemical properties of diabetic bone resulting in improvement of bone strength at the material level. Therefore, specific inhibition of this pathway at the receptor level shows potential as a therapeutic target for diabetic patients suffering from bone diseases such as osteopenia.

Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients.

PubMed

Björkman, Mikko; Sorva, Antti; Risteli, Juha; Tilvis, Reijo

2008-01-01

to evaluate the effects of vitamin D supplementation on parathyroid function and bone turnover in aged, chronically immobile patients. a randomised double-blind controlled trial. two hundred and eighteen long-term inpatients aged over 65 years. the patients were randomised into treatment groups of I-III, each receiving 0 IU, 400 IU and 1200 IU cholecalciferol per day, respectively. In case of inadequate consumption of dairy products, patients received a daily calcium substitution of 500 mg. plasma concentrations of 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (PTH), amino-terminal propeptide of type I procollagen (PINP), a marker of bone formation, and carboxy-terminal telopeptide of type I collagen (ICTP), a marker of bone resorption, were measured at baseline and after 6 months. the patients (age 84.5 years) were chronically bedridden. The baseline 25-OHD was low (23 nmol/l), correlated inversely with PINP, and tended to associate inversely with PTH. The prevalence of vitamin D deficiency (VDD) (25-OHD < 50 nmol/l) was 98% and PTH was elevated in 23% of the patients. Vitamin D supplementation significantly increased 25-OHD concentrations (124% group II, 204% group III) and decreased PTH (-7% group II, -8% group III). PINP tended to decrease, but ICTP tended to increase, and only their ratio decreased significantly. The tendency of ICTP to increase was inconsistent. Changes in 25-OHD correlated inversely with those in PTH and PINP. vitamin D supplementation has minor effects on PTH and bone turnover in chronically immobilised aged patients with VDD. Further comparative studies and meta-analyses are warranted to elucidate the confounding effects of different mobility levels on the benefits of vitamin D supplementation in patients with differing baseline PTH levels.

Modic changes in lumbar spine: prevalence and distribution patterns of end plate oedema and end plate sclerosis.

PubMed

Xu, Lei; Chu, Bin; Feng, Yang; Xu, Feng; Zou, Yue-Fen

2016-01-01

The purpose of this study is to evaluate the distribution of end plate oedema in different types of Modic change especially in mixed type and to analyze the presence of end plate sclerosis in various types of Modic change. 276 patients with low back pain were scanned with 1.5-T MRI. Three radiologists assessed the MR images by T1 weighted, T2 weighted and fat-saturation T2 weighted sequences and classified them according to the Modic changes. Pure oedematous end plate signal changes were classified as Modic Type I; pure fatty end plate changes were classified as Modic Type II; and pure sclerotic end plate changes as Modic Type III. A mixed feature of both Types I and II with predominant oedematous signal change is classified as Modic I-II, and a mixture of Types I and II with predominant fatty change is classified as Modic II-I. Thus, the mixed types can further be subdivided into seven subtypes: Types I-II, Types II-I, Types I-III, Types III-I, Types II-III, Types III-II and Types I-III. During the same period, 52 of 276 patients who underwent CT and MRI were retrospectively reviewed to determine end plate sclerosis. (1) End plate oedema: of the 2760 end plates (276 patients) examined, 302 end plates showed Modic changes, of which 82 end plates showed mixed Modic changes. The mixed Modic changes contain 92.7% of oedematous changes. The mixed types especially Types I-II and Types II-I made up the majority of end plate oedematous changes. (2) End plate sclerosis: 52 of 276 patients were examined by both MRI and CT. Of the 520 end plates, 93 end plates showed Modic changes, of which 34 end plates have shown sclerotic changes in CT images. 11.8% of 34 end plates have shown Modic Type I, 20.6% of 34 end plates have shown Modic Type II, 2.9% of 34 end plates have shown Modic Type III and 64.7% of 34 end plates have shown mixed Modic type. End plate oedema makes up the majority of mixed types especially Types I-II and Types II-I. The end plate sclerosis on CT images may not just mean Modic Type III but does exist in all types of Modic changes, especially in mixed Modic types, and may reflect vertebral body mineralization rather than change in the bone marrow. End plate oedema and end plate sclerosis are present in a large proportion of mixed types.

Is trabecular bone permeability governed by molecular ordering-induced fluid viscosity gain? Arguments from re-evaluation of experimental data in the framework of homogenization theory.

PubMed

Abdalrahman, T; Scheiner, S; Hellmich, C

2015-01-21

It is generally agreed on that trabecular bone permeability, a physiologically important quantity, is governed by the material׳s (vascular or intertrabecular) porosity as well as by the viscosity of the pore-filling fluids. Still, there is less agreement on how these two key factors govern bone permeability. In order to shed more light onto this somewhat open issue, we here develop a random homogenization scheme for upscaling Poiseuille flow in the vascular porosity, up to Darcy-type permeability of the overall porous medium "trabecular bone". The underlying representative volume element of the macroscopic bone material contains two types of phases: a spherical, impermeable extracellular bone matrix phase interacts with interpenetrating cylindrical pore channel phases that are oriented in all different space directions. This type of interaction is modeled by means of a self-consistent homogenization scheme. While the permeability of the bone matrix equals to zero, the permeability of the pore phase is found through expressing the classical Hagen-Poiseuille law for laminar flow in the format of a "micro-Darcy law". The upscaling scheme contains pore size and porosity as geometrical input variables; however, they can be related to each other, based on well-known relations between porosity and specific bone surface. As two key results, validated through comprehensive experimental data, it appears (i) that the famous Kozeny-Carman constant (which relates bone permeability to the cube of the porosity, the square of the specific surface, as well as to the bone fluid viscosity) needs to be replaced by an again porosity-dependent rational function, and (ii) that the overall bone permeability is strongly affected by the pore fluid viscosity, which, in case of polarized fluids, is strongly increased due to the presence of electrically charged pore walls. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Diagnosis and treatment of Gaucher disease in Croatia].

PubMed

Mrsić, Mirando

2007-05-01

Gaucher disease is the most common lysosomal storage disorder. Incidence of disease is around 1:40-60,000 inhabitants and it is assuming that in Croatia we have 20-30 patients with Morbus Gaucher. Morbus Gaucher is recognized in three types. Type I or so called non-neuropatic from is most common in Europe while so called neuropatic forms (type II and III) are much rare (5-10%). Type II and III are characterized by central nervous system involvement and usually are diagnosed in childhood. Disease manifestations are observed in various human organs. The most common disease features are involved liver, spleen, bones, lungs and brain. Enzyme replacement therapy with imiglucerase (Cerezyme) is now day's therapeutic gold standard. Imiglucerase prevents progressive manifestation of disease and patients have normal life. Cost of the treatment is high due to the cost of the recombinant technology which was used to product imiglucerase. The cost of the enzyme replacement therapy is 150-200,000 EUR per year for imiglucerase in a typical adult patient. Because of high cost for the patient treatment Ministry of Health of Republic of Croatia, and Croatian Health Insurance Company in year 2002. established a special program for so called "Expensive drug treatment". This program covering treatment costs for patients with inherited metabolic disorders, adenosine deaminase deficiency, chronic myeloid leukemia, AIDS, multiple sclerosis, juvenile arthritis and ovarian cancer. Until now 11 adult patients and 2 children with Gaucher disease were diagnosed in Croatia and all are on enzyme replacement therapy with imiglucerase. According to our experience administration of imiglucerase decreased spleen and liver size and number of bone pain crisis as well as normalization of platelet and red blood cells. Administration of the imiglucerase do no revert bone changes e.g. avascular hip necrosis or vertebra collapses, but prevent further bone deterioration. According to this, treatment with imiglucerase should be started immediately after establishing diagnosis to prevent irreversible changes on human organs.

Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton

PubMed Central

Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

2015-01-01

Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. PMID:25779879

Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton.

PubMed

Chen, Shan; Grover, Monica; Sibai, Tarek; Black, Jennifer; Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

2015-05-01

Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development. Copyright © 2015 Elsevier Inc. All rights reserved.

Immunolocalization of matrix metalloproteinase-13 on bone surface under osteoclasts in rat tibia.

PubMed

Nakamura, Hiroaki; Sato, Ginga; Hirata, Azumi; Yamamoto, Toshio

2004-01-01

Matrix metalloproteinase (MMP)-13 (an interstitial collagenase also called collagenase 3) is involved in degradation of extracellular matrix in various tissues. Using immunohistochemistry and Western blotting, we investigated localization of MMP-13 in rat tibia, to clarify the role of MMP-13 in bone resorption. MMP-13 reactivity was mainly seen on bone surfaces under osteoclasts, and in some osteocytes and their lacunae near osteoclasts. However, immunoreactivity was not seen in chondrocytes or osteoclasts. MMP-13 was also localized on cement lines in the epiphysis. In the growth plate erosion zone, perivascular cells showed MMP-13 reactivity. Immunoelectron microscopy revealed that MMP-13 was localized on the bone surfaces, under the ruffled borders and some clear zones of osteoclasts. Gold-labeled MMP-13 was closely associated with collagen fibrils. Gold labeling was also detected in Golgi apparatus of osteocytes adjacent to osteoclasts and bone lining cells. Western blotting showed that MMP-13 was mainly associated with mineralized bone matrix. These findings suggest that MMP-13 synthesized and secreted by osteoblast-lineage cells is localized under the ruffled borders of osteoclasts. MMP-13 may play an important role in degradation of type I collagen in bone matrix, acting in concert with cathepsin K and MMP-9 produced by osteoclasts. MMP-13 in perivascular cells may be involved in removal of cartilage matrix proteins such as type II collagen and aggrecan.

Inhibition of TGF–β signaling in subchondral bone mesenchymal stem cells attenuates osteoarthritis

PubMed Central

Zhen, Gehua; Wen, Chunyi; Jia, Xiaofeng; Li, Yu; Crane, Janet L.; Mears, Simon C.; Askin, Frederic B.; Frassica, Frank J.; Chang, Weizhong; Yao, Jie; Nayfeh, Tariq; Johnson, Carl; Artemov, Dmitri; Chen, Qianming; Zhao, Zhihe; Zhou, Xuedong; Cosgarea, Andrew; Carrino, John; Riley, Lee; Sponseller, Paul; Wan, Mei; Lu, William Weijia; Cao, Xu

2013-01-01

Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for osteoarthritis due to limited understanding of osteoarthritis pathogenesis. We show that TGF–β1 is activated in the subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) osteoarthritis mouse model. TGF–β1 concentrations also increased in human osteoarthritis subchondral bone. High concentrations of TGF–β1 induced formation of nestin+ mesenchymal stem cell (MSC) clusters leading to aberrant bone formation accompanied by increased angiogenesis. Transgenic expression of active TGF–β1 in osteoblastic cells induced osteoarthritis. Inhibition of TGF–β activity in subchondral bone attenuated degeneration of osteoarthritis articular cartilage. Notably, knockout of the TGF–β type II receptor (TβRII) in nestin+ MSCs reduced development of osteoarthritis in ACLT mice. Thus, high concentrations of active TGF–β1 in the subchondral bone initiated the pathological changes of osteoarthritis, inhibition of which could be a potential therapeutic approach. PMID:23685840

Paralysis Episodes in Carbonic Anhydrase II Deficiency.

PubMed

Al-Ibrahim, Alia; Al-Harbi, Mosa; Al-Musallam, Sulaiman

2003-01-01

Carbonic anhydrase II (CAII) deficiency is an autosomal recessive disorder manifest by osteopetrosis, renal tubular acidosis, and cerebral calcification. Other features include growth failure and mental retardation. Complications of the osteopetrosis include frequent bone fractures, cranial nerve compression, and dental mal-occlusion. A hyper-chloremic metabolic acidosis, sometimes with hypokalemia, occurs due to renal tubular acidosis that may be proximal, distal, or more commonly, the combined type. Such patients may present with global hypotonia, muscle weakness or paralysis. We report a case of CA II deficiency with recurrent attacks of acute paralysis which was misdiagnosed initially as Guillian-Barre syndrome.

Three-Dimensional Bio-Printed Scaffold Sleeves With Mesenchymal Stem Cells for Enhancement of Tendon-to-Bone Healing in Anterior Cruciate Ligament Reconstruction Using Soft-Tissue Tendon Graft.

PubMed

Park, Sin Hyung; Choi, Yeong-Jin; Moon, Sang Won; Lee, Byung Hoon; Shim, Jin-Hyung; Cho, Dong-Woo; Wang, Joon Ho

2018-01-01

To investigate the efficacy of the insertion of 3-dimensional (3D) bio-printed scaffold sleeves seeded with mesenchymal stem cells (MSCs) to enhance osteointegration between the tendon and tunnel bone in anterior cruciate ligament (ACL) reconstruction in a rabbit model. Scaffold sleeves were fabricated by 3D bio-printing. Before ACL reconstruction, MSCs were seeded into the scaffold sleeves. ACL reconstruction with hamstring tendon was performed on both legs of 15 adult rabbits (aged 12 weeks). We implanted 15 bone tunnels with scaffold sleeves with MSCs and implanted another 15 bone tunnels with scaffold sleeves without MSCs before passing the graft. The specimens were harvested at 4, 8, and 12 weeks. H&E staining, immunohistochemical staining of type II collagen, and micro-computed tomography of the tunnel cross-sectional area were evaluated. Histologic assessment was conducted with a histologic scoring system. In the histologic assessment, a smooth bone-to-tendon transition through broad fibrocartilage formation was identified in the treatment group, and the interface zone showed abundant type II collagen production on immunohistochemical staining. Bone-tendon healing histologic scores were significantly higher in the treatment group than in the control group at all time points. Micro-computed tomography at 12 weeks showed smaller tibial (control, 9.4 ± 0.9 mm 2 ; treatment, 5.8 ± 2.9 mm 2 ; P = .044) and femoral (control, 9.6 ± 2.9 mm 2 ; treatment, 6.0 ± 1.0 mm 2 ; P = .03) bone-tunnel areas in the treated group than in the control group. The 3D bio-printed scaffold sleeve with MSCs exhibited excellent results in osteointegration enhancement between the tendon and tunnel bone in ACL reconstruction in a rabbit model. If secure biological healing between the tendon graft and tunnel bone can be induced in the early postoperative period, earlier, more successful rehabilitation may be facilitated. Three-dimensional bio-printed scaffold sleeves with MSCs have the potential to accelerate bone-tendon healing in ACL reconstruction. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Dual specificity of activin type II receptor ActRIIb in dorso-ventral patterning during zebrafish embryogenesis.

PubMed

Nagaso, H; Suzuki, A; Tada, M; Ueno, N

1999-04-01

Members of the transforming growth factor-beta (TGF-beta) superfamily are thought to regulate specification of a variety of tissue types in early embryogenesis. These effects are mediated through a cell surface receptor complex, consisting of two classes of ser/thr kinase receptor, type I and type II. In the present study, cDNA encoding zebrafish activin type II receptors, ActRIIa and ActRIIb was cloned and characterized. Overexpression of ActRIIb in zebrafish embryos caused dorsalization of embryos, as observed in activin-overexpressing embryos. However, in blastula stage embryos, ActRIIb induced formation of both dorsal and ventro-lateral mesoderm. It has been suggested that these inducing signals from ActRIIb are mediated through each specific type I receptor, TARAM-A and BMPRIA, depending on activin and bone morphogenetic protein (BMP), respectively. In addition, it was shown that a kinase-deleted form of ActRIIb (dnActRIIb) suppressed both activin- and BMP-like signaling pathways. These results suggest that ActRIIb at least has dual roles in both activin and BMP signaling pathways during zebrafish embryogenesis.

Osteoporosis and its association with non-gonadal hormones involved in hypertension, adiposity and hyperglycaemia.

PubMed

Poudyal, Hemant; Brown, Lindsay

2013-12-01

Osteoporosis is a high-prevalence disease, particularly in developed countries, and results in high costs both to the individual and to society through associated fragility fractures. There is an urgent need for identification of novel drug targets and development of new anti-osteoporotic agents. Between 30 and 80% of osteoporotic fractures cannot be prevented despite current treatments achieving relative fracture risk reduction of up to 20%, 50%, and 70% for non-vertebral, hip and spine fractures, respectively. Traditionally, the decline in gonadal hormones has been studied as the sole hormonal determinant for the loss of bone mineral density in osteoporosis. However, recent studies have identified receptors for numerous non-gonadal hormones such as PTH, angiotensin II, leptin, adiponectin, insulin and insulin-like growth factor-1 on the osteoblast lineage cells that directly regulate bone turnover. These hormones are also involved in the pathogenesis of metabolic syndrome risk factors, particularly hypertension, type-II diabetes and obesity. By activating their respective receptors on osteoblastic lineage cells, these hormones appear to act through a common mechanism by down-regulating receptors for activation of nuclear factor kappa B ligand (RANKL) and up-regulating osteoprotegerin (OPG) with inverse responses for adiponectin. Receptors for amylin, gastric inhibitory polypeptide and ghrelin and have also been identified on the osteoblast lineage cells although the roles of these receptors in bone turnover are controversial or poorly studied. Moreover, bone turnover may be independently regulated by modulation of osteoclast-osteoblast function and bone marrow adiposity. Leptin appears to be the only hormone that is a known regulator of both bone mineralisation and bone adiposity.

Hydrostatic pressure enhances chondrogenic differentiation of human bone marrow stromal cells in osteochondrogenic medium.

PubMed

Wagner, Diane R; Lindsey, Derek P; Li, Kelvin W; Tummala, Padmaja; Chandran, Sheena E; Smith, R Lane; Longaker, Michael T; Carter, Dennis R; Beaupre, Gary S

2008-05-01

This study demonstrated the chondrogenic effect of hydrostatic pressure on human bone marrow stromal cells (MSCs) cultured in a mixed medium containing osteogenic and chondrogenic factors. MSCs seeded in type I collagen sponges were exposed to 1 MPa of intermittent hydrostatic pressure at a frequency of 1 Hz for 4 h per day for 10 days, or remained in identical culture conditions but without exposure to pressure. Afterwards, we compared the proteoglycan content of loaded and control cell/scaffold constructs with Alcian blue staining. We also used real-time PCR to evaluate the change in mRNA expression of selected genes associated with chondrogenic and osteogenic differentiation (aggrecan, type I collagen, type II collagen, Runx2 (Cbfa-1), Sox9, and TGF-beta1). With the hydrostatic pressure loading regime, proteoglycan staining increased markedly. Correspondingly, the mRNA expression of chondrogenic genes such as aggrecan, type II collagen, and Sox9 increased significantly. We also saw a significant increase in the mRNA expression of type I collagen, but no change in the expression of Runx2 or TGF-beta1 mRNA. This study demonstrated that hydrostatic pressure enhanced differentiation of MSCs in the presence of multipotent differentiation factors in vitro, and suggests the critical role that this loading regime may play during cartilage development and regeneration in vivo.

Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells.

PubMed

Li, Q S; Meng, F Y; Zhao, Y H; Jin, C L; Tian, J; Yi, X J

2017-08-01

This study aimed to investigate the functional effects of microRNA (miR)-214-5p on osteoblastic cells, which might provide a potential role of miR-214-5p in bone fracture healing. Blood samples were obtained from patients with hand fracture or intra-articular calcaneal fracture and from healthy controls (HCs). Expression of miR-214-5p was monitored by qRT-PCR at day 7, 14 and 21 post-surgery. Mouse osteoblastic MC3T3-E1 cells were transfected with antisense oligonucleotides (ASO)-miR-214-5p, collagen type IV alpha 1 (COL4A1) vector or their controls; thereafter, cell viability, apoptotic rate, and the expression of collagen type I alpha 1 (COL1A1), type II collagen (COL-II), and type X collagen (COL-X) were determined. Luciferase reporter assay, qRT-PCR, and Western blot were performed to ascertain whether COL4A1 was a target of miR-214-5p. Plasma miR-214-5p was highly expressed in patients with bone fracture compared with HCs after fracture (p < 0.05 or p < 0.01). Inhibition of miR-214-5p increased the viability of MC3T3-E1 cells and the expressions of COL1A1 and COL-X, but decreased the apoptotic rate and COL-II expression (p < 0.05 or p < 0.01). COL4A1 was a target of miR-214-5p, and was negatively regulated by miR-214-5p (p < 0.05 or p < 0.01). Overexpression of COL4A1 showed a similar impact on cell viability, apoptotic rate, and COL1A1, COL-II, and COL-X expressions inhibiting miR-214-5p (p < 0.01). Inhibition of miR-214-5p promotes cell survival and extracellular matrix (ECM) formation of osteoblastic MC3T3-E1 cells by targeting COL4A1. Cite this article: Q. S. Li, F. Y. Meng, Y. H. Zhao, C. L. Jin, J. Tian, X. J. Yi. Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells. Bone Joint Res 2017;6:464-471. DOI: 10.1302/2046-3758.68.BJR-2016-0208.R2. © 2017 Yi et al.

Influence of collagen-fibril-based coatings containing decorin and biglycan on osteoblast behavior.

PubMed

Douglas, Timothy; Hempel, Ute; Mietrach, Carolin; Viola, Manuela; Vigetti, Davide; Heinemann, Sascha; Bierbaum, Susanne; Scharnweber, Dieter; Worch, Hartmut

2008-03-01

Collagen is used as a scaffold material for tissue engineering as well as a coating material for implants with a view to enhancing osseointegration by mimicry of the bone extracellular matrix in vivo. The biomimicry strategy can be taken further by incorporating the small leucine-rich proteoglycans (SLRPs) decorin and biglycan, which are expressed in bone. Both bind to fibrils during fibrillogenesis in vitro. In this study, the ability of collagen types I, II, and III to bind decorin and biglycan was compared. Collagen type II bound significantly more SLRPs in fibrils than collagen I and III, with more biglycan than decorin bound by all three collagen types. Therefore, type II fibrils with bound decorin or biglycan or neither were used to coat titanium surfaces. Bioavailability of SLRPs was confirmed by direct ELISA after SLRP biotinilation. The in vitro behavior of osteoblasts from rat calvaria (rOs) and human knee (hOs) cultured on different surfaces was compared. Proliferation and collagen synthesis were determined. Also, the influence of SLRPs on the formation of focal adhesions by rO was investigated. Biglycan enhanced the formation of focal adhesions after 2 and 24 h. Decorin and biglycan affected rO and hO proliferation and collagen synthesis differently. Biglycan stimulated hO proliferation significantly but had no effect on rO proliferation, and also inhibited rO collagen synthesis significantly while not affecting hO collagen synthesis. Decorin promoted hO proliferation slightly but did not influence rO proliferation. The results could be relevant when designing implant coatings or tissue engineering scaffolds. (c) 2007 Wiley Periodicals, Inc.

Effect of celastrol on bone structure and mechanics in arthritic rats.

PubMed

Cascão, Rita; Vidal, Bruno; Jalmari Finnilä, Mikko Arttu; Lopes, Inês Pascoal; Teixeira, Rui Lourenço; Saarakkala, Simo; Moita, Luis Ferreira; Fonseca, João Eurico

2017-01-01

Rheumatoid arthritis (RA) is characterised by chronic inflammation leading to articular bone and cartilage damage. Despite recent progress in RA management, adverse effects, lack of efficacy and economic barriers to treatment access still limit therapeutic success. Therefore, safer and less expensive treatments that control inflammation and bone resorption are needed. We have previously shown that celastrol is a candidate for RA treatment. We have observed that it inhibits both interleukin (IL)-1β and tumor necrosis factor (TNF) in vitro, and that it has anti-inflammatory properties and ability to decrease synovial CD68+ macrophages in vivo. Herein our goal was to evaluate the effect of celastrol in local and systemic bone loss. Celastrol was administrated intraperitoneally at a dose of 1 µg/g/day to female Wistar adjuvant-induced arthritic rats. Rats were sacrificed after 22 days of disease progression, and blood, femurs, tibiae and paw samples were collected for bone remodelling markers quantification, 3-point bending test, micro-CT analysis, nanoindentation and Fourier transform infrared spectroscopy measurements, and immunohistochemical evaluation. We have observed that celastrol preserved articular structures and decreased the number of osteoclasts and osteoblasts present in arthritic joints. Moreover, celastrol reduced tartrate-resistant acid phosphatase 5b, procollagen type 1 amino-terminal propeptide and C terminal crosslinked telopeptide of type II collagen serum levels. Importantly, celastrol prevented bone loss and bone microarchitecture degradation. Celastrol also preserved bone nanoproperties and mineral content. Additionally, animals treated with celastrol had less fragile bones, as depicted by an increase in maximum load and yield displacement. These results suggest that celastrol reduces both bone resorption and cartilage degradation, and preserves bone structural properties.

Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone

PubMed Central

Cui, Zhuang; Crane, Janet; Xie, Hui; Jin, Xin; Zhen, Gehua; Li, Changjun; Xie, Liang; Wang, Long; Bian, Qin; Qiu, Tao; Wan, Mei; Xie, Min; Ding, Sheng; Yu, Bin; Cao, Xu

2016-01-01

Objectives Examine whether osteoarthritis (OA) progression can be delayed by halofuginone in anterior cruciate ligament transection (ACLT) rodent models. Methods 3-month-old male C57BL/6J (wild type; WT) mice and Lewis rats were randomised to sham-operated, ACLT-operated, treated with vehicle, or ACLT-operated, treated with halofuginone. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Immunostaining, flow cytometry, RT-PCR and western blot analyses were conducted to detect relative protein and RNA expression. Bone micro CT (μCT) and CT-based microangiography were quantitated to detect alterations of microarchitecture and vasculature in tibial subchondral bone. Results Halofuginone attenuated articular cartilage degeneration and subchondral bone deterioration, resulting in substantially lower OARSI scores. Specifically, we found that proteoglycan loss and calcification of articular cartilage were significantly decreased in halofuginone-treated ACLT rodents compared with vehicle-treated ACLT controls. Halofuginone reduced collagen X (Col X), matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS 5) and increased lubricin, collagen II and aggrecan. In parallel, halofuginone-attenuated uncoupled subchondral bone remodelling as defined by reduced subchondral bone tissue volume, lower trabecular pattern factor (Tb.pf) and increased thickness of subchondral bone plate compared with vehicle-treated ACLT controls. We found that halofuginone exerted protective effects in part by suppressing Th17-induced osteoclastic bone resorption, inhibiting Smad2/3-dependent TGF-β signalling to restore coupled bone remodelling and attenuating excessive angiogenesis in subchondral bone. Conclusions Halofuginone attenuates OA progression by inhibition of subchondral bone TGF-β activity and aberrant angiogenesis as a potential preventive therapy for OA. PMID:26470720

Designer Self-Assembling Peptide Nanofiber Scaffolds Containing Link Protein N-Terminal Peptide Induce Chondrogenesis of Rabbit Bone Marrow Stem Cells

PubMed Central

Wang, Baichuan; Sun, Caixia; Shao, Zengwu; Yang, Shuhua; Che, Biao; Wu, Qiang; Liu, Jianxiang

2014-01-01

Designer self-assembling peptide nanofiber hydrogel scaffolds have been considered as promising biomaterials for tissue engineering because of their excellent biocompatibility and biofunctionality. Our previous studies have shown that a novel designer functionalized self-assembling peptide nanofiber hydrogel scaffold (RLN/RADA16, LN-NS) containing N-terminal peptide sequence of link protein (link N) can promote nucleus pulposus cells (NPCs) adhesion and three-dimensional (3D) migration and stimulate biosynthesis of type II collagen and aggrecan by NPCs in vitro. The present study has extended these investigations to determine the effects of this functionalized LN-NS on bone marrow stem cells (BMSCs), a potential cell source for NP regeneration. Although the functionalized LN-NS cannot promote BMSCs proliferation, it significantly promotes BMSCs adhesion compared with that of the pure RADA16 hydrogel scaffold. Moreover, the functionalized LN-NS remarkably stimulates biosynthesis and deposition of type II collagen and aggrecan. These data demonstrate that the functionalized peptide nanofiber hydrogel scaffold containing link N peptide as a potential matrix substrate will be very useful in the NP tissue regeneration. PMID:25243141

Effect of recombinant insulin-like growth factor-1 treatment on short-term linear growth in a child with Majewski osteodysplastic primordial dwarfism type II and hepatic insufficiency.

PubMed

Faienza, Maria Felicia; Acquafredda, Angelo; D'Aniello, Mariangela; Soldano, Lucia; Marzano, Flaviana; Ventura, Annamaria; Cavallo, Luciano

2013-01-01

We report the case of a boy affected by severe intrauterine and postnatal growth retardation, microcephaly, facial dysmorphisms and postnecrotic cirrhosis, diagnosed at birth as having Seckel syndrome, and subsequently confirmed as Majewski osteodysplastic primordial dwarfism type II (MOPD II) on the basis of clinical and radiological features of skeletal dysplasia. At our observation (6 years 7 months) he presented height -10.3 standard deviation score (SDS), weight -22.1 SDS, head circumference -8 SDS, delayed bone age of 4 years with respect to chronological age. In consideration of the low levels of insulin-like growth factor-1 (IGF-1) as well as of hepatic insufficiency, we started the treatment with recombinant human IGF-1 (rhIGF-1) at the dose of 0.04 mg/kg in 2 doses/day, with an increase of 0.04 mg/kg after 1 week until the maximum dose of 0.12 mg/kg. We observed an early response to rhIGF-1 treatment, with a shift of height velocity from 1.8 cm/year (-4.6 SDS) at 4 cm/year (-1.9 SDS), and an increase in bone age of 1.5 years during the first 6 months. rhIGF-1 treatment does not seem to be able to replace the physiological action of IGF-1 in patients with MOPD II and hepatic insufficiency, however, it seems to preserve the typical growth pattern of MOPD II patients, avoiding a further widening of the growth deficiency in these subjects.

Growth of severely hypoplastic phalanges and metacarpals in symbrachydactyly: an experimental study in mice.

PubMed

Kanauchi, Yumiko; Takahara, Masatoshi; Harada, Mikio; Ogino, Toshihiko

2008-11-01

Severely hypoplastic phalanges and metacarpals in symbrachydactyly are often associated with a delay or failure of primary ossification evident by radiography at birth. However, little is known about the ossification pattern and further growth of severely hypoplastic bones in symbrachydactyly. To clarify this mechanism, we observed development during ossification of the hypoplastic phalanges in brachypodism mice (which carry functional null mutations of growth differentiation factor 5 and exhibit hypoplastic phalanges) as a model of the bone hypoplasia in symbrachydactyly. Forelimbs of wild-type and brachypodism mice from embryonic day 16.5 to 21 days after birth were sectioned. We used radiography to examine the progression of ossification; safranin O fast green-iron hematoxylin staining and in situ hybridization for type II collagen to demonstrate cartilage; the transferase-mediated nick end-labeling assay to identify apoptosis; and tartrate-resistant acid phosphatase staining to demonstrate osteoclastic activity. In brachypodism mice, radiography showed markedly delayed ossification of the proximal phalanges in comparison with wild-type mice. Safranin O staining and type II collagen in situ hybridization showed that the cartilage anlagen of the proximal phalanges were extremely small, with diffuse endochondral ossification throughout, resulting in lack of growth plate and chondroepiphysis formation. Apoptotic cells were present under the perichondrium on the plantar side of the proximal phalanges from day 7 after birth and had spread randomly by day 14. Diffuse osteoclastic activity was evident throughout the proximal phalanges from days 7 to 14 after birth. These results indicate that severely hypoplastic proximal phalanges in brachypodism mice, although showing an endochondral ossification pattern, lack a growth plate and have no potential for secondary growth. These findings may be relevant to the treatment of symbrachydactyly with severely hypoplastic bones, which are not evident radiographically at birth.

Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro.

PubMed

Ying, Xiaozhou; Zhang, Wei; Cheng, Shaowen; Nie, Pengfei; Cheng, Xiaojie; Shen, Yue; Wang, Wei; Xue, Enxing; Chen, Qingyu; Kou, Dongquan; Peng, Lei; Zhang, Yu; Lu, Chuanzhu

2012-11-01

Nicotine has been reported that it has a dose-dependent effect on matrix mineralization by human bone marrow cells. However, there is no relevant research concerning on chondrogenic differentiation potential of bone marrow stromal stem cells (BMSCs) treated with nicotine in vitro. The aims of the study were to examine the effects of nicotine (0, 10(-7), 10(-6) and 10(-5) M) on the proliferation and chondrogenic differentiation of BMSCs from three healthy donors in vitro. BMSCs proliferation was analyzed by CCK8 assay and real-time polymerase chain reaction was used to assay the expression of type II collagen, aggrecan, type I collagen and type X collagen. The proteoglycan content was stained by Alcian blue, and the sulfated glycosaminoglycan (sGAG) content of BMSCs was quantified spectrofluorometrically using dimethylmethylene blue. The cell viability was not significantly impaired until up to a concentration of 10(-5) M nicotine. Nicotine promoted the proliferation and enhanced the expression of type II collagen at the level up to 10(-6) M (P < 0.05). The expression of aggrecan was reduced at the concentration of 10(-5) M nicotine at day 14 (P < 0.05), and there was no significant difference in aggrecan gene expression at 10(-7) and 10(-6) M nicotine levels compared to control group (n.s.). Also the fibroblastic and hypertrophic gene expressions were down-regulated in the chondrogenic medium with 10(-7)-10(-5) M nicotine (P < 0.05). It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing chondrogenic differentiation capacity of BMSCs in cell-based cartilage tissue engineering. Also these results indicate that nicotine maybe a potentially useful drug for the treatment of Osteoarthritis.

Bone Sialoproteins and Breast Cancer Detection

DTIC Science & Technology

2005-07-01

Fig. 8 shows (DSPP) gene within the critical dentinogenesis imperfecta type 11 and BSP with an intact RGD bridging MMP-2 to its cell-surface dentin...sialoprotein (BSP) and the pivotal transcriptional oebter Gasy seler I Freedma NcWe of BiselarMa.tMatix regulator of osteogenesis , Cbfal/Runx2, in malignant...potential the pathogenesis of dentinogenesis imperfecta type II. Genomics 1997; diagnostic biomarker for ovarian cancer. JAMA 2002;287:1671-9. 42:38-45

Dual delivery of rhPDGF-BB and bone marrow mesenchymal stromal cells expressing the BMP2 gene enhance bone formation in a critical-sized defect model.

PubMed

Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2013-11-01

Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis.

Spiral ligament and stria vascularis changes in cochlear otosclerosis: effect on hearing level.

PubMed

Doherty, Joni K; Linthicum, Fred H

2004-07-01

To investigate the effect of changes within the spiral ligament and stria vascularis on hearing in cochlear otosclerosis, we examined spiral ligament hyalinization, stria vascularis atrophy, and sensory hearing loss in cochlear otosclerosis and described changes in ion transport molecule expression. Retrospective. Tertiary referral center. Thirty-two cochleae from 24 temporal bone donors with histologic evidence of cochlear otosclerosis, including spiral ligament hyalinization. Audiography. Measurements of spiral ligament width, stria vascularis, and bone-conduction thresholds were compared by the amount of hyalinization. Expression of the ion transport molecules Na,K-ATPase, connexin 26, and carbonic anhydrase II were assessed by immunohistochemical techniques. Hyalinization most often involved the posterior basal turn (88%) and the posterior middle turn (27%). Spiral ligament hyalinization correlated significantly with stria vascularis atrophy in the posterior middle turn of the cochlea (rho = -0.63, p < 0.01). There was a trend toward a significant association in the posterior basal turn (rho = -0.31, p < 0.08). Bone-conduction thresholds at 2,000 and 4,000 Hz were significantly associated with the amount of stria vascularis atrophy (rho = -0.44, -0.40, p < 0.05). In addition, we observed decreased immunostaining for both carbonic anhydrase II with Type I fibrocytes and Na,K-ATPase with stria vascularis and Type II and Type IV fibrocytes of the spiral ligament in cochlear otosclerosis sections compared with normal cochlea. Na,K-ATPase staining within the stria vascularis was further decreased in the presence of spiral ligament hyalinization. No significant differences were seen with connexin 26 immunostaining. However, immunostaining results were somewhat inconsistent. These data suggest that spiral ligament structure and function are essential for stria vascularis survival. In addition, dampened expression of ion transport molecules within the spiral ligament and stria vascularis may disrupt potassium ion recycling, resulting in loss of endocochlear potential and sensory hearing loss.

Effects of extracellular matrix proteins on macrophage differentiation, growth, and function: comparison of liquid and agar culture systems

NASA Technical Reports Server (NTRS)

Armstrong, J. W.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

1994-01-01

Both spaceflight and skeletal unloading suppress the haematopoietic differentiation of macrophages (Sonnenfeld et al., Aviat. Space Environ. Med., 61:648-653, 1990; Armstrong et al., J. Appl. Physiol., 75:2734-2739, 1993). The mechanism behind this reduction in haematopoiesis has yet to be elucidated. However, changes in bone marrow extracellular matrix (ECM) may be involved. To further understand the role of ECM products in macrophage differentiation, we have performed experiments evaluating the effects of fibronectin, laminin, collagen type I, and collagen type IV on macrophage development and function. Bone marrow-derived macrophages cultured on four different ECM substrates in liquid culture medium showed less growth than those cultured on plastic. Significant morphological differences were seen on each of the substrates used. Phenotypically and functionally, as measured by class II major histocompatibility molecule (MHCII) expression, MAC-2 expression, and the secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), these macrophages were similar. In contrast, bone marrow-derived macrophages cultured in suspension, using agar, showed no difference in growth when exposed to ECM proteins. However, IL-6 and TNF-alpha secretion was affected by fibronectin, laminin, collagen type I, and collagen type IV in a concentration-dependent manner. We conclude that the ECM products fibronectin, laminin, collagen type I, and collagen type IV have profound effects on macrophage development and function. Additionally, we suggest that an ECM-supplemented agar culture system provides an environment more analogous to in vivo bone marrow than does a traditional liquid culture system.

Biomechanical and histologic basis of osseodensification drilling for endosteal implant placement in low density bone. An experimental study in sheep.

PubMed

Lahens, Bradley; Neiva, Rodrigo; Tovar, Nick; Alifarag, Adham M; Jimbo, Ryo; Bonfante, Estevam A; Bowers, Michelle M; Cuppini, Marla; Freitas, Helora; Witek, Lukasz; Coelho, Paulo G

2016-10-01

A bone drilling concept, namely osseodensification, has been introduced for the placement of endosteal implants to increase primary stability through densification of the osteotomy walls. This study investigated the effect of osseodensification on the initial stability and early osseointegration of conical and parallel walled endosteal implants in low density bone. Five male sheep were used. Three implants were inserted in the ilium, bilaterally, totaling 30 implants (n=15 conical, and n=15 parallel). Each animal received 3 implants of each type, inserted into bone sites prepared as follows: (i) regular-drilling (R: 2mm pilot, 3.2mm, and 3.8mm twist drills), (ii) clockwise osseodensification (CW), and (iii) counterclockwise (CCW) osseodensification drilling with Densah Bur (Versah, Jackson, MI, USA): 2.0mm pilot, 2.8mm, and 3.8mm multi-fluted burs. Insertion torque as a function of implant type and drilling technique, revealed higher values for osseodensification relative to R-drilling, regardless of implant macrogeometry. A significantly higher bone-to-implant contact (BIC) for both osseodensification techniques (p<0.05) was observed compared to R-drilling. There was no statistical difference in BIC as a function of implant type (p=0.58), nor in bone-area-fraction occupancy (BAFO) as a function of drilling technique (p=0.22), but there were higher levels of BAFO for parallel than conic implants (p=0.001). Six weeks after surgery, new bone formation along with remodeling sites was observed for all groups. Bone chips in proximity with the implants were seldom observed in the R-drilling group, but commonly observed in the CW, and more frequently under the CCW osseodensification technique. In low-density bone, endosteal implants present higher insertion torque levels when placed in osseodensification drilling sites, with no osseointegration impairment compared to standard subtractive drilling methods. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Descriptive study of activity of the bone marrow donor registry and bank from the Murcia Region (southeast of Spain) (1994-2004)].

PubMed

Rojas Montero, G M; Alvarez López, M R; López Bermejo, A; Moya Quiles, M R; Muro Amador, M

2006-11-01

To perform a descriptive study of the activity of the Bank of marrow donors from Murcia Region. All donors in the Bank of bone marrow from 1994 until 2004 (n=3137). This study analysed the number of donors, their origin and, performed donor searches activity. Donors were typed by serological microlymphocytotoxicity and molecular PCR-SSO and PCR-SSP techniques. The Bank of bone marrow has 3,137 voluntary donors typed in low- and high-resolution. A total of 680 donor searches have been realized. The origin of the donors according to several Areas of Health in which the Autonomous Community of Murcia is divided, is the following one: Area I (28%), Area II (18 %), Area III (23 %), Area IV (6 %), Area VI (10 %) and other provinces (12%). An increase is observed in the number of annual donors as well as an increase very marked of donor searches that are realized every year, especially in 2004.

Inhibition of bone resorption in vitro by antisense RNA and DNA molecules targeted against carbonic anhydrase II or two subunits of vacuolar H(+)-ATPase.

PubMed Central

Laitala, T; Väänänen, H K

1994-01-01

The bone resorbing cells, osteoclasts, express high levels of carbonic anhydrase II (CA II) and vacuolar H(+)-ATPase (V-ATPase) during bone resorption. We have used antisense RNA and DNA molecules targeted against CA II, and against 16- and 60-kD subunits of vacuolar H(+)-ATPase (V-ATPase), to block the expression of these proteins in vitro. Osteoclastic bone resorption was studied in two in vitro culture systems: release of 45Calcium from prelabeled newborn mouse calvaria cultures, and resorption pit assays performed with rat osteoclasts cultured on bovine bone slices. Both antisense RNA and DNA against CA II and the V-ATPase were used to compare their specificities as regards inhibiting bone resorption in vitro. The antisense molecules inhibited the synthesis of these proteins by decreasing the amounts of mRNA in the cells in a highly specific manner. In osteoclast cultures treated with the 16-kD V-ATPase antisense RNA, acidification of an unknown population of intracellular vesicles was highly stimulated. The acidification of these vesicles was not sensitive to amiloride or bafilomycin A1. This suggests the existence of a back-up system for acidification of intracellular vesicles, when the expression of the V-ATPase is blocked. Our results further indicate that blocking the expression of CA II and V-ATPase with antisense RNA or DNA leads to decreased bone resorption. Images PMID:8200964

Repulsive Guidance Molecules (RGMs) and Neogenin in Bone Morphogenetic Protein (BMP) signaling

PubMed Central

Tian, Chenxi; Liu, Jun

2015-01-01

Summary Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGFβ) superfamily. BMPs mediate a highly conserved signal transduction cascade through the type I and type II serine/threonine kinase receptors and intracellular Smad proteins. The BMP pathway regulates multiple developmental and homeostatic processes. Mutations in this pathway can cause various diseases in humans, such as skeletal disorders, cardiovascular diseases and various cancers. Multiple levels of regulation, including extracellular regulation, help to ensure proper spatiotemporal control of BMP signaling in the right cellular context. The family of repulsive guidance molecules (RGMs) and the type I trans-membrane protein neogenin, a paralog of DCC (Deleted in Colorectal Cancer), have been implicated in modulating the BMP pathway. In this review, we discuss the properties and functions of RGM proteins and neogenin, focusing on their roles in the modulation of BMP signal transduction. PMID:23740870

A predictive radiological analysis of short stems versus both shortened and long stems in primary hip replacement: A case-control study of 100 cases of Metha versus ABG II and Omnifit HA at 2-8years' follow-up.

PubMed

Epinette, J-A; Brax, M; Chammaï, Y

2017-11-01

Short hip stems, intended to conserve bone stock and ensure a more physiological distribution of stress in the femur under loading, are meeting with renewed interest. Radiologic semiology is not known exactly, particularly in relation to conventional implants; we therefore conducted a case-control study of 3 types of implant differing only in stem length: short, shortened or long. The aim was: (1) to compare radiographic aspects, (2) to attempt to systematize medium-term radiologic status for the 3 types, and (3) to assess the impact of radiographic aspect on loosening and revision rates. The short Metha stem is better adapted to the recipient bone than longer stems, without sacrificing stability. A prospective series comprising the first 100 selected cases of hip replacement using the short Metha stem was compared to two other series of 100 "long" (Omnifit HA) and 100 "shortened" (ABG II) stems at comparable follow-up: 4.05±1.44years (range: 2-8years) for Metha, 4.48±0.97years (range: 2-8years) for Omnifit, and 4.75±2.07years (range: 2-8years) for ABG II. Selection criteria in this initial phase were very strict: young age and/or high activity level, with good bone stock and femoral morphology suited to fitting a Metha stem (no "stovepipe" or "champagne-flute" femurs), for which 12.8% of primary hip replacements were selected. Matching was performed by sampling on criteria of age, gender, body-mass index and etiology. Radiographic parameters were compared between the short stem group and the two control groups and classified according to Engh-Massin score (10 points for fixation and 17 for stability). The short Metha stem provided excellent fixation scores: 7.65/10, versus 7.16 (P=0.003) and 5.92 (P=0.0001) for ABG II and Omnifit, respectively. Likewise, stability was scored 14.23/17 for Metha, vs. 14.51 (NS) and 11.83 (P=0.0001) respectively, and the total score was higher for Metha (21.88/27) than ABG II (21.67; P=0.03) or, more particularly, Omnifit (17.83; P=0.0001). The Metha stem was never associated with thigh pain or periprosthetic fracture. 8-year survival was 100%, without significant difference with respect to ABG II (100%; NS) or Omnifit (98.8%; 95% CI: 0.964-1; NS). The apparent radiologic superiority of the short Metha stem requires long-term confirmation in non-selected series. Meanwhile, Metha can be asserted to have demonstrated optimal compromise between lasting bone anchorage and respect of bone physiology under loading at medium term. III, case-control study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Direct bone morphogenetic protein 2 and Indian hedgehog gene transfer for articular cartilage repair using bone marrow coagulates.

PubMed

Sieker, J T; Kunz, M; Weißenberger, M; Gilbert, F; Frey, S; Rudert, M; Steinert, A F

2015-03-01

Bone morphogenetic protein 2 (BMP-2, encoded by BMP2) and Indian hedgehog protein (IHH, encoded by IHH) are well known regulators of chondrogenesis and chondrogenic hypertrophy. Despite being a potent chondrogenic factor BMP-2 was observed to induce chondrocyte hypertrophy in osteoarthritis (OA), growth plate cartilage and adult mesenchymal stem cells (MSCs). IHH might induce chondrogenic differentiation through different intracellular signalling pathways without inducing subsequent chondrocyte hypertrophy. The primary objective of this study is to test the efficacy of direct BMP2 and IHH gene delivery via bone marrow coagulates to influence histological repair cartilage quality in vivo. Vector-laden autologous bone marrow coagulates with 10(11) adenoviral vector particles encoding BMP2, IHH or the Green fluorescent protein (GFP) were delivered to 3.2 mm osteochondral defects in the trochlea of rabbit knees. After 13 weeks the histological repair cartilage quality was assessed using the ICRS II scoring system and the type II collagen positive area. IHH treatment resulted in superior histological repair cartilage quality than GFP controls in all of the assessed parameters (with P < 0.05 in five of 14 assessed parameters). Results of BMP2 treatment varied substantially, including severe intralesional bone formation in two of six joints after 13 weeks. IHH gene transfer is effective to improve repair cartilage quality in vivo, whereas BMP2 treatment, carried the risk intralesional bone formation. Therefore IHH protein can be considered as an attractive alternative candidate growth factor for further preclinical research and development towards improved treatments for articular cartilage defects. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Tendon healing in a bone tunnel. Part II: Histologic analysis after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep.

PubMed

Weiler, Andreas; Hoffmann, Reinhard F G; Bail, Hermann J; Rehm, Oliver; Südkamp, Norbert P

2002-02-01

Tendon-to-bone healing of soft-tissue grafts has been described to progress by the development of a fibrous interzone that undergoes a maturation process leading to the development of an indirect type of ligament insertion. Previous studies used extra-articular models or fixation far away from the joint line; thus, no data are available investigating tendon-to-bone healing of a soft-tissue graft fixed anatomically. Therefore, we studied the tendon-to-bone healing of the anatomic soft-tissue graft interference fit fixation in a model of anterior cruciate ligament (ACL) reconstruction in sheep. Animal study. Thirty-five mature sheep underwent ACL reconstruction with an autologous Achilles tendon split graft. Grafts were directly fixed with biodegradable poly-(D,L-lactide) interference screws. Animals were euthanized after 6, 9, 12, 24, and 52 weeks and histologic evaluations were performed. Undecalcified specimens were evaluated under normal and polarized light. Additionally, animals received a polychrome sequential labeling (tetracycline, xylenol orange, and calcein green) to determine bone growth per time under fluorescent light. Intratunnel histologic findings at 6 weeks showed a tendon-bone junction with only a partial fibrous interzone between the graft tissue and the surrounding bone. A mature intratunnel tendon-bone junction with a zone of fibrocartilage was found at 9 to 12 weeks. At the tunnel entrance site a wide regular ligamentous insertion site was seen in all specimens after 24 weeks. This insertion showed regular patterns such as the direct type of insertion of a normal ligament with a dense basophilic transition zone consisting of mineralized cartilage. A fibrous interzone between the graft tissue and the bone tunnel was only partially developed, which is in contrast to all previous studies in which nonanatomic fixation was used. Thus, it is reasonable to assume that the tendon-to-bone healing in the present study may progress partially by direct-contact healing without the development of a fibrous interzone. To our knowledge, this is the first report describing the development of a direct type of ligament insertion after ACL replacement with a soft-tissue graft. This is in contrast to previous studies reporting the development of an indirect type of insertion when using nonanatomic fixation far away from the joint line. Thus, histologic data strongly indicate that anatomic interference fit fixation is beneficial for tendon-to-bone incorporation by leading to the development of a direct type of ligament insertion.

Polarized type 2 alloreactive CD4+ and CD8+ donor T cells fail to induce experimental acute graft-versus-host disease.

PubMed

Krenger, W; Snyder, K M; Byon, J C; Falzarano, G; Ferrara, J L

1995-07-15

Acute graft-vs-host disease (GVHD) is thought to be mediated by alloreactive T cells with a type 1 cytokine phenotype. To prevent the development of acute GVHD, we have successfully polarized mature donor T cells toward a type 2 cytokine phenotype ex-vivo by incubating them with murine rIL-4 in a primary MLC. Polarized type 2 T cells were then transplanted with T cell-depleted bone marrow cells into irradiated recipients across either MHC class II (bm12-->C57BL/6) or class I (bm1-->C57BL/6) barriers, and the intensity of GVHD was measured by assessment of several in vitro and in vivo parameters. The injection of polarized type 2 T cells abrogated the mitogen-induced production of IFN-gamma by splenocytes from transplanted hosts on day 13 after bone marrow transplantation (BMT). Injection of polarized type 2 T cells failed to induce secretion of the effector phase cytokine TNF-alpha by splenocytes stimulated with LPS both in vitro and in vivo, and survival of transplanted mice after i.v. injection with LPS was significantly improved. Furthermore, cell-mixing experiments revealed that polarized type 2 T cells were able to inhibit type 1 cytokine responses induced by naive T cells after BMT. These data demonstrate that both polarized CD4+ and CD8+ type 2 alloreactive donor T cells can be generated in vitro from mature T cell populations. These cells function in vivo to inhibit type 1 T cell responses, and such inhibition attenuates the systemic morbidity of GVHD after BMT across both MHC class II or class I barriers in mice.

Operative Treatment of Fifth Metatarsal Jones Fractures (Zones II and III) in the NBA.

PubMed

O'Malley, Martin; DeSandis, Bridget; Allen, Answorth; Levitsky, Matthew; O'Malley, Quinn; Williams, Riley

2016-05-01

Proximal fractures of the fifth metatarsal (zone II and III) are common in the elite athlete and can be difficult to treat because of a tendency toward delayed union, nonunion, or refracture. The purpose of this case series was to report our experience in treating 10 NBA players, determine the healing rate, return to play, refracture rate, and role of foot type in these athletes. The records of 10 professional basketball players were retrospectively reviewed. Seven athletes underwent standard percutaneous internal fixation with bone marrow aspirate concentrate (BMAC) whereas the other 3 had open bone grafting primarily in addition to fixation and BMAC. Radiographic features evaluated included fourth-fifth intermetatarsal, fifth metatarsal lateral deviation, calcaneal pitch, and metatarsus adductus angles. Radiographic healing was observed at an overall average of 7.5 weeks and return to play was 9.8 weeks. Three athletes experienced refractures. There were no significant differences in clinical features or radiographic measurements except that the refracture group had the highest metatatarsus adductus angles. Most athletes were pes planus and 9 of 10 had a bony prominence under the fifth metatarsal styloid. This is the largest published series of operatively treated professional basketball players who exemplify a specific patient population at high risk for fifth metatarsal fracture. These players were large and possessed a unique foot type that seemed to be associated with increased risk of fifth metatarsal fracture and refracture. This foot type had forefoot metatarsus adductus and a fifth metatarsal that was curved with a prominent base. We continue to use standard internal fixation with bone marrow aspirate but advocate additional prophylactic open bone grafting in patients with high fourth-to-fifth intermetatarsal, fifth metatarsal lateral deviation, and metatarsus adductus angles as well as prominent fifth metatarsal styloids in order to improve fracture healing and potentially decrease the risk of refracture. Level IV, case series. © The Author(s) 2016.

In Vitro Expression of the Extracellular Matrix Components Aggrecan, Collagen Types I and II by Articular Cartilage-Derived Chondrocytes.

PubMed

Schneevoigt, J; Fabian, C; Leovsky, C; Seeger, J; Bahramsoltani, M

2017-02-01

The extracellular matrix (ECM) of hyaline cartilage is perfectly suited to transmit articular pressure load to the subchondral bone. Pressure is transferred by a high amount of aggrecan-based proteoglycans and collagen type II fibres in particular. After any injury, the hyaline cartilage is replaced by fibrocartilage, which is low in proteoglycans and contains collagen type I predominantly. Until now, long-term results of therapeutic procedures including cell-based therapies like autologous chondrocyte transplantation (ACT) lead to a replacement tissue meeting the composition of fibrocartilage. Therefore, it is of particular interest to discover how and to what extent isolation and in vitro cultivation of chondrocytes affect the cells and their expression of ECM components. Hyaline cartilage-derived chondrocytes were cultivated in vitro and observed microscopically over a time period of 35 days. The expression of collagen type I, collagen type II and aggrecan was analysed using RT-qPCR and Western blot at several days of cultivation. Chondrocytes presented a longitudinal shape for the entire cultivation period. While expression of collagen type I prevailed within the first days, only prolonged cultivation led to an increase in collagen type II and aggrecan expression. The results indicate that chondrocyte isolation and in vitro cultivation lead to a dedifferentiation at least to the stage of chondroprogenitor cells. © 2016 Blackwell Verlag GmbH.

Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the integrin-linked kinase in chondrocytes.

PubMed

Terpstra, Leonieke; Prud'homme, Josée; Arabian, Alice; Takeda, Shu; Karsenty, Gérard; Dedhar, Shoukat; St-Arnaud, René

2003-07-07

Chondrocyte proliferation and differentiation requires their attachment to the collagen type II-rich matrix of developing bone. This interaction is mediated by integrins and their cytoplasmic effectors, such as the integrin-linked kinase (ILK). To elucidate the molecular mechanisms whereby integrins control these processes, we have specifically inactivated the ILK gene in growth plate chondrocytes using the Cre-lox methodology. Mice carrying an ILK allele flanked by loxP sites (ILK-fl) were crossed to transgenic mice expressing the Cre recombinase under the control of the collagen type II promoter. Inactivation of both copies of the ILK-fl allele lead to a chondrodysplasia characterized by a disorganized growth plate and to dwarfism. Expression of chondrocyte differentiation markers such as collagen type II, collagen type X, Indian hedgehog and the PTH-PTHrP receptor was normal in ILK-deficient growth plates. In contrast, chondrocyte proliferation, assessed by BrdU or proliferating cell nuclear antigen labeling, was markedly reduced in the mutant growth plates. Cell-based assays showed that integrin-mediated adhesion of primary cultures of chondrocytes from mutant animals to collagen type II was impaired. ILK inactivation in chondrocytes resulted in reduced cyclin D1 expression, and this most likely explains the defect in chondrocyte proliferation observed when ILK is inactivated in growth plate cells.

Estrogenic Activity Including Bone Enhancement and Effect on Lipid Profile of Luteolin-7-O-glucoside Isolated from Trifolium alexandrinum L. in Ovariectomized Rats.

PubMed

Ammar, N M; El-Hawary, S S; Mohamed, D A; El-Halawany, A M; El-Anssary, A A; El-Kassem, L T Abou; Hussein, R A; Jaleel, G A Abdel; El-Dosoky, A H

2016-05-01

Luteolin-7-O-glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin-7-O-glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone-specific alkaline phosphatase, plasma osteocalsin, type I procollagen N-terminal, and C-telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Fracture characterization of human cortical bone under mode II loading using the end-notched flexure test.

PubMed

Silva, F G A; de Moura, M F S F; Dourado, N; Xavier, J; Pereira, F A M; Morais, J J L; Dias, M I R; Lourenço, P J; Judas, F M

2017-08-01

Fracture characterization of human cortical bone under mode II loading was analyzed using a miniaturized version of the end-notched flexure test. A data reduction scheme based on crack equivalent concept was employed to overcome uncertainties on crack length monitoring during the test. The crack tip shear displacement was experimentally measured using digital image correlation technique to determine the cohesive law that mimics bone fracture behavior under mode II loading. The developed procedure was validated by finite element analysis using cohesive zone modeling considering a trapezoidal with bilinear softening relationship. Experimental load-displacement curves, resistance curves and crack tip shear displacement versus applied displacement were used to validate the numerical procedure. The excellent agreement observed between the numerical and experimental results reveals the appropriateness of the proposed test and procedure to characterize human cortical bone fracture under mode II loading. The proposed methodology can be viewed as a novel valuable tool to be used in parametric and methodical clinical studies regarding features (e.g., age, diseases, drugs) influencing bone shear fracture under mode II loading.

Co-culture of chondrocytes and bone marrow mesenchymal stem cells in vitro enhances the expression of cartilaginous extracellular matrix components.

PubMed

Qing, Chang; Wei-ding, Cui; Wei-min, Fan

2011-04-01

Chondrocytes and bone marrow mesenchymal stem cells (BMSCs) are frequently used as seed cells in cartilage tissue engineering. In the present study, we determined if the co-culture of rabbit articular chondrocytes and BMSCs in vitro promotes the expression of cartilaginous extracellular matrix and, if so, what is the optimal ratio of the two cell types. Cultures of rabbit articular chondrocytes and BMSCs were expanded in vitro and then cultured individually or at a chondrocyte:BMSC ratio of 4:1, 2:1, 1:1, 1:2, 1:4 for 21 days and cultured in DMEM/F12. BMSCs were cultured in chondrogenic induction medium. Quantitative real-time RT-PCR and Western blot were used to evaluate gene expression. In the co-cultures, type II collagen and aggrecan expression increased on days 14 and 21. At the mRNA level, the expression of type II collagen and aggrecan on day 21 was much higher in the 4:1, 2:1, and 1:1 groups than in either the articular chondrocyte group or the induced BMSC group, and the best ratio of co-culture groups seems to be 2:1. Also on day 21, the expression of type II collagen and aggrecan proteins in the 2:1 group was much higher than in all other groups. The results demonstrate that the co-culture of rabbit chondrocytes and rabbit BMSCs at defined ratios can promote the expression of cartilaginous extracellular matrix. The optimal cell ratio appears to be 2:1 (chondrocytes:BMSCs). This approach has potential applications in cartilage tissue engineering since it provides a protocol for maintaining and promoting seed-cell differentiation and function.

Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease

PubMed Central

Knott, L.; Avery, N.C.; Hollander, A.P.; Tarlton, J.F.

2011-01-01

Summary Objective To examine effects of high omega-3 (n-3) polyunsaturated fatty acid (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig model, and to further characterise pathogenesis in this model. Modern diets low in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly including OA. However, n-3 is also thought to increases bone density, which is a possible contributing factor in OA. Therefore we aim to determine the net influence of n-3 in disease development. Method OA-prone Dunkin-Hartley (DH) Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and subchondral bone pathology by histology, and biochemistry, including collagen cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase, glycosaminoglycan (GAG), and denatured type II collagen. Results Dietary n-3 reduced disease in OA-prone animals. Most cartilage parameters were modified by n-3 diet towards those seen in the non-pathological BS2 strain – significantly active MMP-2, lysyl-pyridinoline and total collagen cross-links – the only exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG content was higher and denatured type II lower in the n-3 group. Subchondral bone parameters in the DH n-3 group also changed towards those seen in the non-pathological strain, significantly calcium:phosphate ratios and epiphyseal bone density. Conclusion Dietary n-3 PUFA reduced OA in the prone strain, and most disease markers were modified towards those of the non-OA strain, though not all significantly so. Omega-3 did not increase markers of pathology in either strain. PMID:21723952

BMP type II receptors have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism.

PubMed

Mayeur, Claire; Leyton, Patricio A; Kolodziej, Starsha A; Yu, Binglan; Bloch, Kenneth D

2014-09-25

Expression of hepcidin, the hepatic hormone controlling iron homeostasis, is regulated by bone morphogenetic protein (BMP) signaling. We sought to identify which BMP type II receptor expressed in hepatocytes, ActR2a or BMPR2, is responsible for regulating hepcidin gene expression. We studied Bmpr2 heterozygous mice (Bmpr2(+/-)), mice with hepatocyte-specific deficiency of BMPR2, mice with global deficiency of ActR2a, and mice in which hepatocytes lacked both BMPR2 and ActR2a. Hepatic hepcidin messenger RNA (mRNA) levels, serum hepcidin and iron levels, and tissue iron levels did not differ in wild-type mice, Bmpr2(+/-) mice, and mice in which either BMPR2 or ActR2a was deficient. Deficiency of both BMP type II receptors markedly reduced hepatic hepcidin gene expression and serum hepcidin levels leading to severe iron overload. Iron injection increased hepatic hepcidin mRNA levels in mice deficient in either BMPR2 or ActR2a, but not in mice deficient in both BMP type II receptors. In addition, in mouse and human primary hepatocytes, deficiency of both BMPR2 and ActR2a profoundly decreased basal and BMP6-induced hepcidin gene expression. These results suggest that BMP type II receptors, BMPR2 and ActR2a, have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism. © 2014 by The American Society of Hematology.

The ACE-2/Ang1-7/Mas cascade enhances bone structure and metabolism following angiotensin-II type 1 receptor blockade.

PubMed

Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

2017-07-15

The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p.o.) for 6 weeks. A specific Mas receptor blocker (A-779) was delivered via mini-osmotic pumps during the losartan treatment period. Serum and urine bone metabolism biomarker levels were measured. Bone trabecular and cortical morphometry were quantified in distal femurs, whereas mineral contents were estimated in ashed bones, serum and urine. Finally, the expression of RAS components, the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) was determined. Losartan significantly improved the elevated bone metabolism marker levels and altered trabecular and cortical structures in OVX animals, and restored normal urinary and skeletal mineral levels. Mas receptor inhibition significantly abolished all osteo-protective effects of losartan and enhanced the deleterious effects of OVX. Losartan enhanced OVX-induced up-regulation of ACE-1, AngII, angiotensin type 1 (AT 1 ) receptor and RANKL expression, and increased ACE-2, Ang1-7, Mas and OPG expression in OVX animals. However, A-779 significantly eradicated the effects of losartan on RAS components and RANKL/OPG expression. Thus, Ang1-7 are involved in the osteo-preservative effects of losartan via Mas receptor, which may add therapeutic value to this well-known antihypertensive agent. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone

PubMed Central

Lanocha-Arendarczyk, Natalia; Kosik-Bogacka, Danuta I.; Kalisinska, Elzbieta; Sokolowski, Sebastian; Kolodziej, Lukasz; Budis, Halina; Safranow, Krzysztof; Kot, Karolina; Ciosek, Zaneta; Tomska, Natalia; Galant, Katarzyna

2016-01-01

The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V), chromium (Cr), and calcium (Ca) and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C), cortical bone (CB), and spongy bone (SB) samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i) the amount of consumed beer and (ii) seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone). PMID:27294138

Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone.

PubMed

Lanocha-Arendarczyk, Natalia; Kosik-Bogacka, Danuta I; Kalisinska, Elzbieta; Sokolowski, Sebastian; Kolodziej, Lukasz; Budis, Halina; Safranow, Krzysztof; Kot, Karolina; Ciosek, Zaneta; Tomska, Natalia; Galant, Katarzyna

2016-01-01

The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V), chromium (Cr), and calcium (Ca) and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C), cortical bone (CB), and spongy bone (SB) samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i) the amount of consumed beer and (ii) seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone).

Augmentation of tibial plateau fractures with an injectable bone substitute: CERAMENT™. Three year follow-up from a prospective study.

PubMed

Iundusi, Riccardo; Gasbarra, Elena; D'Arienzo, Michele; Piccioli, Andrea; Tarantino, Umberto

2015-05-13

Reduction of tibial plateau fractures and maintain a level of well aligned congruent joint is key to a satisfactory clinical outcome and is important for the return to pre-trauma level of activity. Stable internal fixation support early mobility and weight bearing. The augmentation with bone graft substitute is often required to support the fixation to mantain reduction. For these reasons there has been development of novel bone graft substitutes for trauma applications and in particular synthetic materials based on calcium phosphates and/or apatite combined with calcium sulfates. Injectable bone substitutes can optimize the filling of irregular bone defects. The purpose of this study was to assess the potential of a novel injectable bone substitute CERAMENT™|BONE VOID FILLER in supporting the initial reduction and preserving alignment of the joint surface until fracture healing. From June 2010 through May 2011 adult patients presenting with acute, closed and unstable tibial plateau fractures which required both grafting and internal fixation, were included in a prospective study with percutaneous or open reduction and internal fixation (ORIF) augmented with an injectable ceramic biphasic bone substitute CERAMENT™|BONE VOID FILLER (BONESUPPORT™, Lund, Sweden) to fill residual voids. Clinical follow up was performed at 1, 3, 9 and 12 months and any subsequent year; including radiographic analysis and Rasmussen system for knee functional grading. Twenty four patients, balanced male-to-female, with a mean age of 47 years, were included and followed with an average of 44 months (range 41-52 months). Both Schatzker and Müller classifications were used and was type II or 41-B3 in 7 patients, type III or 41-B2 in 12 patients, type IV or 41-C1 in 2 patients and type VI or 41-C3 in 3 patients, respectively. The joint alignement was satisfactory and manteined within a range of 2 mm, with an average of 1.18 mm. The mean Rasmussen knee function score was 26.5, with 14 patients having an excellent result and the remaining 10 with a good result. It can be concluded that radiological and clinical outcome was satisfactory and obtained in all cases without complications. This injectable novel biphasic hydroxyapatite and calcium sulfate ceramic material is a valuable armamentarium in the treatment of trauma where bone graft is required.

Bone morphogenetic protein 9 (BMP9) and BMP10 enhance tumor necrosis factor-α-induced monocyte recruitment to the vascular endothelium mainly via activin receptor-like kinase 2.

PubMed

Mitrofan, Claudia-Gabriela; Appleby, Sarah L; Nash, Gerard B; Mallat, Ziad; Chilvers, Edwin R; Upton, Paul D; Morrell, Nicholas W

2017-08-18

Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis. The aim of this study was to investigate the roles of BMP9 and BMP10 in mediating monocyte-endothelial interactions using an in vitro flow adhesion assay. Herein, we report that whereas BMP9/BMP10 alone had no effect on monocyte recruitment, at higher concentrations both cytokines synergized with tumor necrosis factor-α (TNFα) to increase recruitment to the vascular endothelium. The BMP9/BMP10-mediated increase in monocyte recruitment in the presence of TNFα was associated with up-regulated expression levels of E-selectin, vascular cell adhesion molecule (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Using siRNAs to type I and II BMP receptors and the signaling intermediaries (Smads), we demonstrated a key role for ALK2 in the BMP9/BMP10-induced surface expression of E-selectin, and both ALK1 and ALK2 in the up-regulation of VCAM-1 and ICAM-1. The type II receptors, BMPR-II and ACTR-IIA were both required for this response, as was Smad1/5. The up-regulation of cell surface adhesion molecules by BMP9/10 in the presence of TNFα was inhibited by LDN193189, which inhibits ALK2 but not ALK1. Furthermore, LDN193189 inhibited monocyte recruitment induced by TNFα and BMP9/10. BMP9/10 increased basal IκBα protein expression, but did not alter p65/RelA levels. Our findings suggest that higher concentrations of BMP9/BMP10 synergize with TNFα to induce the up-regulation of endothelial selectins and adhesion molecules, ultimately resulting in increased monocyte recruitment to the vascular endothelium. This process is mediated mainly via the ALK2 type I receptor, BMPR-II/ACTR-IIA type II receptors, and downstream Smad1/5 signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Extracellular matrix components and culture regimen selectively regulate cartilage formation by self-assembling human mesenchymal stem cells in vitro and in vivo.

PubMed

Ng, Johnathan; Wei, Yiyong; Zhou, Bin; Burapachaisri, Aonnicha; Guo, Edward; Vunjak-Novakovic, Gordana

2016-12-09

Cartilage formation from self-assembling mesenchymal stem cells (MSCs) in vitro recapitulate important cellular events during mesenchymal condensation that precedes native cartilage development. The goal of this study was to investigate the effects of cartilaginous extracellular matrix (ECM) components and culture regimen on cartilage formation by self-assembling human MSCs in vitro and in vivo. Human bone marrow-derived MSCs (hMSCs) were seeded and compacted in 6.5-mm-diameter transwell inserts with coated (type I, type II collagen) or uncoated (vehicle) membranes, at different densities (0.5 × 10 6 , 1.0 × 10 6 , 1.5 × 10 6 per insert). Pellets were formed by aggregating hMSCs (0.25 × 10 6 ) in round-bottomed wells. All tissues were cultured for up to 6 weeks for in vitro analyses. Discs (cultured for 6, 8 or 10 weeks) and pellets (cultured for 10 weeks) were implanted subcutaneously in immunocompromised mice to evaluate the cartilage stability in vivo. Type I and type II collagen coatings enabled cartilage disc formation from self-assembling hMSCs. Without ECM coating, hMSCs formed dome-shaped tissues resembling the pellets. Type I collagen, expressed in the prechondrogenic mesenchyme, improved early chondrogenesis versus type II collagen. High seeding density improved cartilage tissue properties but resulted in a lower yield of disc formation. Discs and pellets exhibited compositional and organizational differences in vitro and in vivo. Prolonged chondrogenic induction of the discs in vitro expedited endochondral ossification in vivo. The outcomes of cartilage tissues formed from self-assembling MSCs in vitro and in vivo can be modulated by the control of culture parameters. These insights could motivate new directions for engineering cartilage and bone via a cartilage template from self-assembling MSCs.

Effects of intermittent versus continuous parathyroid hormone administration on condylar chondrocyte proliferation and differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Qi; Wan, Qilong; Yang, Rongtao

Highlights: Black-Right-Pointing-Pointer Different PTH administration exerts different effects on condylar chondrocyte. Black-Right-Pointing-Pointer Intermittent PTH administration suppresses condylar chondrocyte proliferation. Black-Right-Pointing-Pointer Continuous PTH administration maintains condylar chondrocyte proliferating. Black-Right-Pointing-Pointer Intermittent PTH administration enhances condylar chondrocyte differentiation. -- Abstract: Endochondral ossification is a complex process involving chondrogenesis and osteogenesis regulated by many hormones and growth factors. Parathyroid hormone (PTH), one of the key hormones regulating bone metabolism, promotes osteoblast differentiation and osteogenesis by intermittent administration, whereas continuous PTH administration inhibits bone formation. However, the effects of PTH on chondrocyte proliferation and differentiation are still unclear. In this study, intermittent PTH administration presentedmore » enhanced effects on condylar chondrocyte differentiation and bone formation, as demonstrated by increased mineral nodule formation and alkaline phosphatase (ALP) activity, up-regulated runt-related transcription factor 2 (RUNX2), ALP, collagen type X (COL10a1), collagen type I (COL1a1), osteocalcin (OCN), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2) and osterix (OSX) mRNA and/or protein expression. On the contrary, continuous PTH administration promoted condylar chondrocyte proliferation and suppressed its differentiation, as demonstrated by up-regulated collagen type II (COL2a1) mRNA expression, reduced mineral nodule formation and down-regulated expression of the mRNAs and/or proteins mentioned above. Our data suggest that PTH can regulate condylar chondrocyte proliferation and differentiation, depending on the type of PTH administration. These results provide new insight into the effects of PTH on condylar chondrocytes and new evidence for using local PTH administration to cure mandibular asymmetry.« less

Two novel mutations of CLCN7 gene in Chinese families with autosomal dominant osteopetrosis (type II).

PubMed

Zheng, Hui; Shao, Chong; Zheng, Yan; He, Jin-Wei; Fu, Wen-Zhen; Wang, Chun; Zhang, Zhen-Lin

2016-07-01

Autosomal dominant osteopetrosis type II (ADO-II) is a heritable bone disorder characterized by osteosclerosis, predominantly involving the spine (vertebral end-plate thickening, or rugger-jersey spine), the pelvis ("bone-within-bone" structures) and the skull base. Chloride channel 7 (CLCN7) has been reported to be the causative gene. In this study, we aimed to identify the pathogenic mutation in four Chinese families with ADO-II. All 25 exons of the CLCN7 gene, including the exon-intron boundaries, were amplified and sequenced directly in four probands from the Chinese families with ADO-II. The mutation site was then identified in other family members and 250 healthy controls. In family 1, a known missense mutation c.296A>G in exon 4 of CLCN7 was identified in the proband, resulting in a tyrosine (UAU) to cysteine (UGU) substitution at p.99 (Y99C); the mutation was also identified in his affected father. In family 2, a novel missense mutation c.865G>C in exon 10 was identified in the proband, resulting in a valine (GUC) to leucine (CUC) substitution at p.289 (V289L); the mutation was also identified in her healthy mother and sister. In family 3, a novel missense mutation c.1625C>T in exon 17 of CLCN7 was identified in the proband, resulting in an alanine (GCG) to valine (GUG) substitution at p.542 (A542V); the mutation was also identified in her father. In family 4, a hot spot, R767W (c.2299C>T, CGG>TGG), in exon 24 was found in the proband which once again proved the susceptibility of the site or the similar genetic background in different races. Moreover, two novel mutations, V289L and A542V, occurred at a highly conserved position, found by a comparison of the protein sequences from eight vertebrates, and were predicted to have a pathogenic effect by PolyPhen-2 software, which showed "probably damaging" with a score of approximately 1. These mutation sites were not identified in 250 healthy controls. Our present findings suggest that the novel missense mutations V289L and A542V in the CLCN7 gene were responsible for ADO-II in the two Chinese families.

[Effect of the middle ear status on the recording of vestibular evoked myogenic potential--VEMP].

PubMed

Kurzyna, Agnieszka; Hassmann-Poznańska, Elzbieta; Topolska, Małgorzata Maria

2005-01-01

The aim of this study was to assess the effect of the middle ear status on the recording of air- and bone-conducted vestibular evoked myogenic potential. Forty eight children were included in the study, ranging in age from 4 to 10 years. All of the children underwent otoscopy, pure tone audiometry, tympanometry and air- and bone-conducted VEMP in response to click. There were 3 groups according to the condition of the middle ear: group I--52 ears (type A and C1 tympanogram, pure tone average < or = 20 dB), group II--23 ears (type C2 and B tympanogram, pure tone average < or = 20 dB), group III--21 (type B tympanogram, pure tone average > 20 dB). The threshold, presence of correct waveform morphology of the response and latency was evaluated. The condition of the middle ear has no significant effect on the recording of VEMP and mean level of the response threshold with bone stimulation, based on the performed studies. However, with air stimulation it has effect on the recording of VEMP, increase of the mean threshold response and shortening of latency p13 and n23.

Severe Clinical Course in a Patient with Congenital Amegakaryocytic Thrombocytopenia Due to a Missense Mutation of the c-MPL Gene.

PubMed

Ok Bozkaya, İkbal; Yaralı, Neşe; Işık, Pamir; Ünsal Saç, Rukiye; Tavil, Betül; Tunç, Bahattin

2015-06-01

Congenital amegakaryocytic thrombocytopenia (CAMT) generally begins at birth with severe thrombocytopenia and progresses to pancytopenia. It is caused by mutations in the thrombopoietin receptor gene, the myeloproliferative leukemia virus oncogene (c-MPL). The association between CAMT and c-MPL mutation type has been reported in the literature. Patients with CAMT have been categorized according to their clinical symptoms caused by different mutations. Missense mutations of c-MPL have been classified as type II and these patients have delayed onset of bone marrow failure compared to type I patients. Here we present a girl with severe clinical course of CAMT II having a missense mutation in exon 4 of the c-MPL gene who was admitted to our hospital with intracranial hemorrhage during the newborn period.

Assessment of Non-Invasive Methods of Measuring Bone Repair in Naval Casualty Victims.

DTIC Science & Technology

1980-02-01

the pin-hole colurnator on a high resolution gamma camera. In addition, the pilot project was necessary to train new technicians who had been hired...after the loss of trained technicians in 1976. Finally, the project was under- taken to help define any problems with regards to radiation contamination...allograft was entirely normal and equivalent to its autogenous control except that its histologic rating was a Type II repair rather than a Type I. In

[Phakomatosis pigmento-vascularis. Report of 2 cases associated with angiodysplasia].

PubMed

Peyron, N; Dereure, O; Bessis, D; Guilhou, J J; Guillot, B

1993-01-01

Phakomatosis pigmentovascularis is an uncommon disease, with a peculiar association of capillary hemangioma and pigmented lesions. Four entities have to date been described (I to IV), with localized (a) or systematical (b) involvement. In this latter subtype, the cutaneous lesions are associated with visceral (eye, central nervous system) and bony abnormalities. We describe two additional cases of phakomatosis pigmentovascularis type II (b) associated with a Klippel-Trenaunay syndrome. These reports emphasize the frequent occurrence of angiodysplasia of the Klippel-Trenaunay or Sturge-Weber-Krabbe type in the systemic subtype, especially II (b). Accordingly, complete investigations are warranted in all cases, with special attention for bones and some internal organs like eye and central nervous system. Pathophysiological hypothesis for phakomatosis pigmentovascularis are discussed.

Alveolar bone thickness and lower incisor position in skeletal Class I and Class II malocclusions assessed with cone-beam computed tomography

PubMed Central

Ucar, Faruk Izzet; Buyuk, Suleyman Kutalmis; Ozer, Torun; Uysal, Tancan

2013-01-01

Objective To evaluate lower incisor position and bony support between patients with Class II average- and high-angle malocclusions and compare with the patients presenting Class I malocclusions. Methods CBCT records of 79 patients were divided into 2 groups according to sagittal jaw relationships: Class I and II. Each group was further divided into average- and high-angle subgroups. Six angular and 6 linear measurements were performed. Independent samples t-test, Kruskal-Wallis, and Dunn post-hoc tests were performed for statistical comparisons. Results Labial alveolar bone thickness was significantly higher in Class I group compared to Class II group (p = 0.003). Lingual alveolar bone angle (p = 0.004), lower incisor protrusion (p = 0.007) and proclination (p = 0.046) were greatest in Class II average-angle patients. Spongious bone was thinner (p = 0.016) and root apex was closer to the labial cortex in high-angle subgroups when compared to the Class II average-angle subgroup (p = 0.004). Conclusions Mandibular anterior bony support and lower incisor position were different between average- and high-angle Class II patients. Clinicians should be aware that the range of lower incisor movement in high-angle Class II patients is limited compared to average- angle Class II patients. PMID:23814708

Alveolar bone thickness and lower incisor position in skeletal Class I and Class II malocclusions assessed with cone-beam computed tomography.

PubMed

Baysal, Asli; Ucar, Faruk Izzet; Buyuk, Suleyman Kutalmis; Ozer, Torun; Uysal, Tancan

2013-06-01

To evaluate lower incisor position and bony support between patients with Class II average- and high-angle malocclusions and compare with the patients presenting Class I malocclusions. CBCT records of 79 patients were divided into 2 groups according to sagittal jaw relationships: Class I and II. Each group was further divided into average- and high-angle subgroups. Six angular and 6 linear measurements were performed. Independent samples t-test, Kruskal-Wallis, and Dunn post-hoc tests were performed for statistical comparisons. Labial alveolar bone thickness was significantly higher in Class I group compared to Class II group (p = 0.003). Lingual alveolar bone angle (p = 0.004), lower incisor protrusion (p = 0.007) and proclination (p = 0.046) were greatest in Class II average-angle patients. Spongious bone was thinner (p = 0.016) and root apex was closer to the labial cortex in high-angle subgroups when compared to the Class II average-angle subgroup (p = 0.004). Mandibular anterior bony support and lower incisor position were different between average- and high-angle Class II patients. Clinicians should be aware that the range of lower incisor movement in high-angle Class II patients is limited compared to average- angle Class II patients.

Reconstructive surgery using interference screw fixation for painful accessory navicular in adult athletes.

PubMed

Miyamoto, Wataru; Takao, Masato; Yamada, Kazuaki; Yasui, Youichi; Matsushita, Takashi

2012-10-01

To examine the effectiveness of a new technique for reattaching the posterior tibial tendon (PTT) using a bone tunnel and interference screw after resection of the accessory navicular for painful accessory navicular (type II) in adult athletes. Ten adult athletes (7 male, 3 female; mean age 30 years, range 23-45) underwent reconstruction using a bone tunnel with an interference screw for a painful accessory navicular. All patients complained of pain on the medial aspect of the foot after eversion sprain during sports activities and radiographs revealed type II accessory navicular. Clinical evaluation with the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS) and visual analogue scale (VAS) before surgery was compared with that at most recent follow up (mean 30 months, range 24-39). Mean AOFAS score improved from a preoperative 62.8 ± 2.9 points (range 61-82) to a postoperative 92.1 ± 7.0 points (range 83-100; p < 0.01). Furthermore, mean VAS score improved from a preoperative 92.5 ± 5.4 points (range 85-100) to a postoperative 4.5 ± 3.8 points (range 0-10; p < 0.01). All patients could return to full sports activity at a mean of 14 weeks (range 12-18) after surgery. The presented technique reconstructs the bone-tendon interface of the PTT at the primary navicular with sufficient fixation after resection of the accessory navicular, which preserves the strength of the PTT in adult athletes with an intractably painful accessory navicular.

Molecular Imaging With Quantum Dots Probing EMT and Prostate Cancer Metastasis in Live Animals

DTIC Science & Technology

2007-10-01

of humanprostate cancer metastasis to human bone. Cancer Res 1999;59(8): 1987 – 1993. 14. Navone NM, Olive M, Ozen M, Davis R, Troncoso P, Tu SM...changing the particle size. J. Am. Chem. Soc. 125, 7100–7106. 27. Kim, S., Fisher, B., Eisler , H. J., and Bawendi, M. (2003) Type-II quantum dots

Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism.

PubMed

Su, W C; Kitagawa, M; Xue, N; Xie, B; Garofalo, S; Cho, J; Deng, C; Horton, W A; Fu, X Y

1997-03-20

The achondroplasia class of chondrodysplasias comprises the most common genetic forms of dwarfism in humans and includes achondroplasia, hypochondroplasia and thanatophoric dysplasia types I and II (TDI and TDII), which are caused by different mutations in a fibroblast growth-factor receptor FGFR3 (ref. 1). The molecular mechanism and the mediators of these FGFR3-related growth abnormalities are not known. Here we show that mutant TDII FGFR3 has a constitutive tyrosine kinase activity which can specifically activate the transcription factor Stat1 (for signal transducer and activator of transcription). Furthermore, expression of TDII FGFR3 induced nuclear translocation of Stat1, expression of the cell-cycle inhibitor p21(WAF1/CIP1), and growth arrest of the cell. Thus, TDII FGFR3 may use Stat1 as a mediator of growth retardation in bone development. Consistent with this, Stat1 activation and increased p21(WAF1/CIP1) expression was found in the cartilage cells from the TDII fetus, but not in those from the normal fetus. Thus, abnormal STAT activation and p21(WAF1/CIP1) expression by the TDII mutant receptor may be responsible for this FGFR3-related bone disease.

[Application of rafting K-wire technique for tibial plateau fractures].

PubMed

Zhang, Xing-zhou; Yu, Wei-zhong; Li, Yun-feng; Liu, Yan-hui

2015-12-01

To summarize application of rafting K-wires technique for tibial plateau fractures. From January 2013 to January 2015,45 patients with tibial plateau fractures were treated by locking plate with rafting K-wires, including 33 males and 12 females with an average of 44.2 years old ranging from 22 to 56 years old. According to Schatzker classification, 6 cases were type II, 8 were type Ill, 4 were type IV, 4 were type V, and 5 were type VI. Allogeneic bone graft were performed for bone defects. All patients were fixed with two to five K-wires. Part of weight loading were encouraged at 3 months after operation,and full weight-loading were done at 5 months after operation. Postoperative complications were observed,and Rasmussen clinical and radiological assessment were used to evaluate clinical results. All Patients were followed up from 10 to 23 months with average of 14 months. According to Rasmussen clinical and radiological assessment, clinical scores 23.58 ± 6.33, radiological scores were 14.00 ± 6.33; and excellent and good rates were 82.2% and 77.8% respectively. Four patients occurred severe osteoporosis and collapse of articular surface; 5 patients occurred traumatic arthritis. Rafting K-wires technique with anatomized armor plate could effective fix and support platform collapse and joint bone fragments, increase support surface area and reduce postoperative reduction loss rate.

Small subchondral drill holes improve marrow stimulation of articular cartilage defects.

PubMed

Eldracher, Mona; Orth, Patrick; Cucchiarini, Magali; Pape, Dietrich; Madry, Henning

2014-11-01

Subchondral drilling is an established marrow stimulation technique. Osteochondral repair is improved when the subchondral bone is perforated with small drill holes, reflecting the physiological subchondral trabecular distance. Controlled laboratory study. A rectangular full-thickness chondral defect was created in the trochlea of adult sheep (n = 13) and treated with 6 subchondral drillings of either 1.0 mm (reflective of the trabecular distance) or 1.8 mm in diameter. Osteochondral repair was assessed after 6 months in vivo by macroscopic, histological, and immunohistochemical analyses and by micro-computed tomography. The application of 1.0-mm subchondral drill holes led to significantly improved histological matrix staining, cellular morphological characteristics, subchondral bone reconstitution, and average total histological score as well as significantly higher immunoreactivity to type II collagen and reduced immunoreactivity to type I collagen in the repair tissue compared with 1.8-mm drill holes. Analysis of osteoarthritic changes in the cartilage adjacent to the defects revealed no significant differences between treatment groups. Restoration of the microstructure of the subchondral bone plate below the chondral defects was significantly improved after 1.0-mm compared to 1.8-mm drilling, as shown by higher bone volume and reduced thickening of the subchondral bone plate. Likewise, the microarchitecture of the drilled subarticular spongiosa was better restored after 1.0-mm drilling, indicated by significantly higher bone volume and more and thinner trabeculae. Moreover, the bone mineral density of the subchondral bone in 1.0-mm drill holes was similar to the adjacent subchondral bone, whereas it was significantly reduced in 1.8-mm drill holes. No significant correlations existed between cartilage and subchondral bone repair. Small subchondral drill holes that reflect the physiological trabecular distance improve osteochondral repair in a translational model more effectively than larger drill holes. These results have important implications for the use of subchondral drilling for marrow stimulation, as they support the use of small-diameter bone-cutting devices. © 2014 The Author(s).

Hyperlipidemia affects multiscale structure and strength of murine femur.

PubMed

Ascenzi, Maria-Grazia; Lutz, Andre; Du, Xia; Klimecky, Laureen; Kawas, Neal; Hourany, Talia; Jahng, Joelle; Chin, Jesse; Tintut, Yin; Nackenhors, Udo; Keyak, Joyce

2014-07-18

To improve bone strength prediction beyond limitations of assessment founded solely on the bone mineral component, we investigated the effect of hyperlipidemia, present in more than 40% of osteoporotic patients, on multiscale structure of murine bone. Our overarching purpose is to estimate bone strength accurately, to facilitate mitigating fracture morbidity and mortality in patients. Because (i) orientation of collagen type I affects, independently of degree of mineralization, cortical bone׳s micro-structural strength; and, (ii) hyperlipidemia affects collagen orientation and μCT volumetric tissue mineral density (vTMD) in murine cortical bone, we have constructed the first multiscale finite element (mFE), mouse-specific femoral model to study the effect of collagen orientation and vTMD on strength in Ldlr(-/-), a mouse model of hyperlipidemia, and its control wild type, on either high fat diet or normal diet. Each µCT scan-based mFE model included either element-specific elastic orthotropic properties calculated from collagen orientation and vTMD (collagen-density model) by experimentally validated formulation, or usual element-specific elastic isotropic material properties dependent on vTMD-only (density-only model). We found that collagen orientation, assessed by circularly polarized light and confocal microscopies, and vTMD, differed among groups and that microindentation results strongly correlate with elastic modulus of collagen-density models (r(2)=0.85, p=10(-5)). Collagen-density models yielded (1) larger strains, and therefore lower strength, in simulations of 3-point bending and physiological loading; and (2) higher correlation between mFE-predicted strength and 3-point bending experimental strength, than density-only models. This novel method supports ongoing translational research to achieve the as yet elusive goal of accurate bone strength prediction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis.

PubMed

Earp, Justin C; Dubois, Debra C; Molano, Diana S; Pyszczynski, Nancy A; Almon, Richard R; Jusko, William J

2008-08-01

A mechanism-based model for pharmacodynamic effects of dexamethasone (DEX) was incorporated into our model for arthritis disease progression in the rat to aid in identification of the primary factors responsible for edema and bone loss. Collagen-induced arthritis was produced in male Lewis rats after injection of type II porcine collagen. DEX was given subcutaneously in single doses of 0.225 or 2.25 mg/kg or 7-day multiple doses of 0.045 or 0.225 mg/kg at 21 days postdisease induction. Effects on disease progression were measured by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST), and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue. Lumbar and femur BMD was determined by PIXImus II dual-energy X-ray absorptiometry. Plasma CST was assayed by high-performance liquid chromatography. Cytokine and GR mRNA were assayed by quantitative real-time polymerase chain reaction. Indirect response models, drug interaction models, transduction processes, and the fifth-generation model of corticosteroid dynamics were integrated and applied using S-ADAPT software to describe how dexamethasone binding to GR can regulate diverse processes. Cytokine mRNA, GR mRNA, plasma CST, and paw edema were suppressed after DEX administration. TNF-alpha mRNA expression and BMD seemed to increase immediately after dosing but were ultimately reduced. Model parameters indicated that IL-6 and IL-1beta were most sensitive to inhibition by DEX. TNF-alpha seemed to primarily influence edema, whereas IL-6 contributed the most to bone loss. Lower doses of corticosteroids may be sufficient to suppress the cytokines most relevant to bone erosion.

Repatriation and Identification of Finnish World War II Soldiers

PubMed Central

Palo, Jukka U.; Hedman, Minttu; Söderholm, Niklas; Sajantila, Antti

2007-01-01

Aim To present a summary of the organization, field search, repatriation, forensic anthropological examination, and DNA analysis for the purpose of identification of Finnish soldiers with unresolved fate in World War II. Methods Field searches were organized, executed, and financed by the Ministry of Education and the Association for Cherishing the Memory of the Dead of the War. Anthropological examination conducted on human remains retrieved in the field searches was used to establish the minimum number of individuals and description of the skeletal diseases, treatment, anomalies, or injuries. DNA tests were performed by extracting DNA from powdered bones and blood samples from relatives. Mitochondrial DNA (mtDNA) sequence comparisons, together with circumstantial evidence, were used to connect the remains to the putative family members. Results At present, the skeletal remains of about a thousand soldiers have been found and repatriated. In forensic anthropological examination, several injuries related to death were documented. For the total of 181 bone samples, mtDNA HVR-1 and HVR-2 sequences were successfully obtained for 167 (92.3%) and 148 (81.8%) of the samples, respectively. Five samples yielded no reliable sequence data. Our data suggests that mtDNA preserves at least for 60 years in the boreal acidic soil. The quality of the obtained mtDNA sequence data varied depending on the sample bone type, with long compact bones (femur, tibia and humerus) having significantly better (90.0%) success rate than other bones (51.2%). Conclusion Although more than 60 years have passed since the World War II, our experience is that resolving the fate of soldiers missing in action is still of uttermost importance for people having lost their relatives in the war. Although cultural and individual differences may exist, our experience presented here gives a good perspective on the importance of individual identification performed by forensic professionals. PMID:17696308

Expression of a partially deleted gene of human type II procollagen (COL2A1) in transgenic mice produces a chondrodysplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vandenberg, P.; Khillan, J.S.; Prockop, D.J.

A minigene version of the human gene for type II procollagen (COL2AI) was prepared that lacked a large central region containing 12 of the 52 exons and therefore 291 of the 1523 codons of the gene. The construct was modeled after sporadic in-frame deletions of collagen genes that cause synthesis of shortened pro{alpha} chains that associate with normal pro{alpha} chains and thereby cause degradation of the shortened and normal pro{alpha} chains through a process called procollagen suicide. The gene construct was used to prepare five lines of transgenic mice expressing the minigene. A large proportion of the mice expressing themore » minigene developed a phenotype of a chondrodysplasia with dwarfism, short and thick limbs, a short snout, a cranial bulge, a cleft palate, and delayed mineralization of bone. A number of mice died shortly after birth. Microscopic examination of cartilage revealed decreased density and organization of collagen fibrils. In cultured chondrocytes from the transgenic mice, the minigene was expressed as shortened pro{alpha}1(II) chains that were disulfide-linked to normal mouse pro{alpha}1(II) chains. Therefore, the phenotype is probably explained by depletion of the endogenous mouse type II procollagen through the phenomenon of procollagen suicide.« less

Ascorbic acid induces alkaline phosphatase, type X collagen, and calcium deposition in cultured chick chondrocytes.

PubMed

Leboy, P S; Vaias, L; Uschmann, B; Golub, E; Adams, S L; Pacifici, M

1989-10-15

During the process of endochondral bone formation, proliferating chondrocytes give rise to hypertrophic chondrocytes, which then deposit a mineralized matrix to form calcified cartilage. Chondrocyte hypertrophy and matrix mineralization are associated with expression of type X collagen and the induction of high levels of the bone/liver/kidney isozyme of alkaline phosphatase. To determine what role vitamin C plays in these processes, chondrocytes derived from the cephalic portion of 14-day chick embryo sternae were grown in the absence or presence of exogenous ascorbic acid. Control untreated cells displayed low levels of type X collagen and alkaline phosphatase activity throughout the culture period. However, cells grown in the presence of ascorbic acid produced increasing levels of alkaline phosphatase activity and type X collagen mRNA and protein. Both alkaline phosphatase activity and type X collagen mRNA levels began to increase within 24 h of ascorbate treatment; by 9 days, the levels of both alkaline phosphatase activity and type X collagen mRNA were 15-20-fold higher than in non-ascorbate-treated cells. Ascorbate treatment also increased calcium deposition in the cell layer and decreased the levels of types II and IX collagen mRNAs; these effects lagged significantly behind the elevation of alkaline phosphatase and type X collagen. Addition of beta-glycerophosphate to the medium increased calcium deposition in the presence of ascorbate but had no effect on levels of collagen mRNAs or alkaline phosphatase. The results suggest that vitamin C may play an important role in endochondral bone formation by modulating gene expression in hypertrophic chondrocytes.

Molecular cloning and chromosomal mapping of bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishikawa, Jun; Kaisho, Tsuneyasu; Tomizawa, Hitoshi

1995-04-10

Bone marrow stromal cells regulate B-cell growth and development through their surface molecules and cytokines. In this study, we generated a mAb, RS38, that recognized a novel human membrane protein, BST-2, expressed on bone marrow stromal cell lines and synovial cell lines. We cloned a cDNA encoding BST-2 from a rheumatoid arthritis-derived synovial cell line. BST-2 is a 30- to 36-kDa type II transmembrane protein, consisting of 180 amino acids. The BST-2 gene (HGMW-approved symbol BST2) is located on chromosome 19p13.2. BST-2 is expressed not only on certain bone marrow stromal cell lines but also on various normal tissues, althoughmore » its expression pattern is different from that of another bone marrow stromal cell surface molecule, BST-1. BST-2 surface expression on fibroblast cell lines facilitated the stromal cell-dependent growth of a murine bone marrow-derived pre-B-cell line, DW34. The results suggest that BST-2 may be involved in pre-B-cell growth. 45 refs., 7 figs., 2 tabs.« less

Skeletal muscle metastases on magnetic resonance imaging: analysis of 31 cases.

PubMed

Li, Qi; Wang, Lei; Pan, Shinong; Shu, Hong; Ma, Ying; Lu, Zaiming; Fu, Xihu; Jiang, Bo; Guo, Qiyong

2016-01-01

To investigate the magnetic resonance imaging (MRI) features of skeletal muscle metastases (SMM). The records of 31 patients with proven SMM were retrospectively reviewed. Clinical history, type of primary malignancy, location of metastases, and MRI features of SMM were evaluated. Based on MRI findings, SMM were divided into three MRI types. The correlation between MRI types with ages and pathology category, between MRI types of SMM and ages, as well as MRI types of SMM and pathology category were analysed with Spearman's rho. The most common primary tumour was genital tumour (25.8%) and bronchial carcinoma (19.4%), and the most common cell type was adenocarcinoma (58.1%). SMM were located in the iliopsoas muscle (26.3%), paravertebral muscles (21.1%), and upper extremity muscles (18.4%). MRI features: (1) Type-I localised lesions (12.90%), round-like mass limited to local regions with heterogeneous iso-signal intensity in T1WI and heterogeneous hyper-intensity in T2WI; (2) Type-II diffuse lesions without bone destruction (35.48%), abnormal diffuse swelling of the muscle with irregular boundaries and slightly hypo- to iso-intensity in T1WI and hyper-intensity in T2WI; and (3) Type-III diffuse lesions with bone destruction (51.61%), distinct irregular lump with iso-intensity in T1WI and heterogeneous hyper-intensity in T2WI with adjacent bone invasion. There was positive correlation between MRI types and ages (r = 0.431, p < 0.05). There were no significant differences of MRI types with pathology category (p > 0.05). SMM features on MRI can be broadly used to classify lesions, which is beneficial for SMM diagnosis.

Skeletal muscle metastases on magnetic resonance imaging: analysis of 31 cases

PubMed Central

Li, Qi; Wang, Lei; Shu, Hong; Ma, Ying; Lu, Zaiming; Fu, Xihu; Jiang, Bo; Guo, Qiyong

2016-01-01

Aim of the study To investigate the magnetic resonance imaging (MRI) features of skeletal muscle metastases (SMM). Material and methods The records of 31 patients with proven SMM were retrospectively reviewed. Clinical history, type of primary malignancy, location of metastases, and MRI features of SMM were evaluated. Based on MRI findings, SMM were divided into three MRI types. The correlation between MRI types with ages and pathology category, between MRI types of SMM and ages, as well as MRI types of SMM and pathology category were analysed with Spearman's rho. Results The most common primary tumour was genital tumour (25.8%) and bronchial carcinoma (19.4%), and the most common cell type was adenocarcinoma (58.1%). SMM were located in the iliopsoas muscle (26.3%), paravertebral muscles (21.1%), and upper extremity muscles (18.4%). MRI features: (1) Type-I localised lesions (12.90%), round-like mass limited to local regions with heterogeneous iso-signal intensity in T1WI and heterogeneous hyper-intensity in T2WI; (2) Type-II diffuse lesions without bone destruction (35.48%), abnormal diffuse swelling of the muscle with irregular boundaries and slightly hypo- to iso-intensity in T1WI and hyper-intensity in T2WI; and (3) Type-III diffuse lesions with bone destruction (51.61%), distinct irregular lump with iso-intensity in T1WI and heterogeneous hyper-intensity in T2WI with adjacent bone invasion. There was positive correlation between MRI types and ages (r = 0.431, p < 0.05). There were no significant differences of MRI types with pathology category (p > 0.05). Conclusions SMM features on MRI can be broadly used to classify lesions, which is beneficial for SMM diagnosis. PMID:27647989

Early failure mechanisms of constrained tripolar acetabular sockets used in revision total hip arthroplasty.

PubMed

Cooke, Christopher C; Hozack, William; Lavernia, Carlos; Sharkey, Peter; Shastri, Shani; Rothman, Richard H

2003-10-01

Fifty-eight patients received an Osteonics constrained acetabular implant for recurrent instability (46), girdlestone reimplant (8), correction of leg lengthening (3), and periprosthetic fracture (1). The constrained liner was inserted into a cementless shell (49), cemented into a pre-existing cementless shell (6), cemented into a cage (2), and cemented directly into the acetabular bone (1). Eight patients (13.8%) required reoperation for failure of the constrained implant. Type I failure (bone-prosthesis interface) occurred in 3 cases. Two cementless shells became loose, and in 1 patient, the constrained liner was cemented into an acetabular cage, which then failed by pivoting laterally about the superior fixation screws. Type II failure (liner locking mechanism) occurred in 2 cases. Type III failure (femoral head locking mechanism) occurred in 3 patients. Seven of the 8 failures occurred in patients with recurrent instability. Constrained liners are an effective method for treatment during revision total hip arthroplasty but should be used in select cases only.

Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro.

PubMed

Xu, Xiu-Ping; He, Hong-Li; Hu, Shu-Ling; Han, Ji-Bin; Huang, Li-Li; Xu, Jing-Yuan; Xie, Jian-Feng; Liu, Ai-Ran; Yang, Yi; Qiu, Hai-Bo

2017-07-12

Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319). To exclude the effect of proliferation on MSC migration, we measured MSC proliferation after stimulation with the same concentration of Ang II. Additionally, we employed the focal adhesion kinase (FAK) inhibitor PF-573228, RhoA inhibitor C3 transferase, Rac1 inhibitor NSC23766, or Cdc42 inhibitor ML141 to investigate the role of cell adhesion proteins and the Rho-GTPase protein family (RhoA, Rac1, and Cdc42) in Ang II-mediated MSC migration. Cell adhesion proteins (FAK, Talin, and Vinculin) were detected by western blot analysis. The Rho-GTPase family protein activities were assessed by G-LISA and F-actin levels, which reflect actin cytoskeletal organization, were detected by using immunofluorescence. Human bone marrow MSCs constitutively expressed AT1R and AT2R. Additionally, Ang II increased MSC migration in an AT2R-dependent manner. Notably, Ang II-enhanced migration was not mediated by Ang II-mediated cell proliferation. Interestingly, Ang II-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased Talin and Vinculin expression. Moreover, RhoA and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. Furthermore, FAK, Talin, and Vinculin activation and F-actin reorganization in response to Ang II were prevented by PD-123319 but not Losartan, indicating that FAK activation and F-actin reorganization were downstream of AT2R. These data indicate that Ang II-AT2R regulates human bone marrow MSC migration by signaling through the FAK and RhoA/Cdc42 pathways. This study provides insights into the mechanisms by which MSCs home to injury sites and will enable the rational design of targeted therapies to improve MSC engraftment.

Skeletal Remains from World War II Mass Grave: from Discovery to Identification

PubMed Central

Definis Gojanović, Marija; Sutlović, Davorka

2007-01-01

Aim To present the process of identification of skeletal remains from a mass grave found on a Dalmatian mountain-range in 2005, which allegedly contained the remains of civilians from Herzegovina killed in the World War II, including a group of 8 Franciscan monks. Methods Excavation of the site in Dalmatian hinterland, near the village of Zagvozd, was accomplished according to archeological procedures. Anthropological analysis was performed to estimate sex, age at death, and height of the individuals, as well as pathological and traumatic changes of the bones. Due to the lack of ante-mortem data, DNA typing using Y-chromosome was performed. DNA was isolated from bones and teeth samples using standard phenol/chloroform/isoamyl alcohol extraction. Two Y-chromosome short tandem repeats (STR) systems were used for DNA quantification and amplification. Typing of polymerase chain reaction (PCR) products was performed on an ABI Prism 310 Genetic Analyzer. PCR typing results were matched with results from DNA analysis of samples collected from the relatives of supposed victims – blood samples from the living relatives and bone samples collected during further exhumation of died parents or relatives of the supposed victims. Results The remains contained 18 almost complete skeletons, with considerable post-mortal damage. All remains were men, mainly middle-aged, with gunshot wounds to the head. DNA analysis and cross-matching of the results with relatives’ data resulted in three positive identifications using the Y-chromosomal short tandem repeat (Y-STR) systems. All of the positively identified remains belonged to the Franciscan friars allegedly killed in Herzegovina and buried at the analyzed site. Conclusion Our analysis of remains from a mass grave from the World War II confirmed the value of patrilineal lineage based on Y-STRs, even when missing persons had left no offspring, as was the case with Franciscan monks. Although this report is primarily focused on the identification of remains from a mass grave, it also emphasizes the role of forensic approach in documenting human right violations. PMID:17696307

Addition of bone morphogenetic protein type 2 to ascorbate and β-glycerophosphate supplementation did not enhance osteogenic differentiation of human adipose-derived stem cells.

PubMed

Cruz, Ariadne Cristiane Cabral; Silva, Mariana Lúcia; Caon, Thiago; Simões, Cláudia Maria Oliveira

2012-01-01

Bone morphogenetic protein type 2 (BMP-2) is a potent local factor, which promotes bone formation and has been used as an osteogenic supplement for mesenchymal stem cells. This study evaluated the effect of a recombinant BMP-2 as well as the endogenous BMP-4 and BMP-7 in the osteogenic differentiation of adipose-derived stem cells (ASCs) in medium supplemented with ascorbate and β-glycerophosphate. Human ASCs were treated with osteogenic medium in the presence (ASCs+OM+BMP-2) or absence (ASCs+OM) of BMP-2. The alkaline phosphatase (ALP) activity was determined and the extracellular matrix mineralization was evaluated by Von Kossa staining and calcium quantification. The expressions of BMP-4, BMP-7, Smad1, Smad4, and phosphorylated Smad1/5/8 were analyzed by western blotting. Relative mRNA expressions of Smad1, BMP receptor type II (BMPR-II), osteonectin, and osteocalcin were evaluated by qPCR. ASCs+OM demonstrated the highest expression of BMP-4 and BMP-7 at days 21 and 7, respectively, the highest levels of BMPR-II mRNA expression at day 28, and the highest levels of Smad1 mRNA at days 14 and 28. ASCs+OM+BMP-2 demonstrated the highest levels of Smad1 mRNA expression at days 1, 7, and 21, the highest expression of Smad1 at day 7, the highest expression of Smad4 at day 14, the highest ALP activity at days 14 and 21, and expression of phosphorylated Smad1/5/8 at day 7. ASCs+OM and ASCs+OM+BMP2 showed similar ALP activity at days 7 and 28, similar osteonectin and osteocalcin mRNA expression at all time periods, and similar calcium depositions at all time periods. We concluded that human ASCs expressed endogenous BMP-4 and BMP-7. Moreover, the supplementation of ASCs with BMP-2 did not increase the level of osteogenic markers in the initial (ALP activity), intermediate (osteonectin and osteocalcin), or final (calcium deposition) phases, suggesting that the exogenous addition of BMP-2 did not improve the in vitro osteogenesis process of human ASCs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ecarot-Charrier, B.; Bouchard, F.; Delloye, C.

Isolated mouse osteoblasts that retain their osteogenic activity in culture were incubated with (35S) sulfate. Two radiolabeled proteins, in addition to proteoglycans, were extracted from the calcified matrix of osteoblast cultures. All the sulfate label in both proteins was in the form of tyrosine sulfate as assessed by amino acid analysis and thin layer chromatography following alkaline hydrolysis. The elution behavior on DEAE-Sephacel of the major sulfated protein and the apparent Mr on sodium dodecyl sulfate gels were characteristic of bone sialoprotein II extracted from rat. This protein was shown to cross-react with an antiserum raised against bovine bone sialoproteinmore » II, indicating that bone sialoprotein II synthesized by cultured mouse osteoblasts is a tyrosine-sulfated protein. The minor sulfated protein was tentatively identified as bone sialoprotein I or osteopontin based on its elution properties on DEAE-Sephacel and anomalous behavior on sodium dodecyl sulfate gels similar to those reported for rat bone sialoprotein I.« less

PPAR-δ Agonist With Mesenchymal Stem Cells Induces Type II Collagen-Producing Chondrocytes in Human Arthritic Synovial Fluid.

PubMed

Heck, Bruce E; Park, Joshua J; Makani, Vishruti; Kim, Eun-Cheol; Kim, Dong Hyun

2017-08-01

Osteoarthritis (OA) is an inflammatory joint disease characterized by degeneration of articular cartilage within synovial joints. An estimated 27 million Americans suffer from OA, and the population is expected to reach 67 million in the United States by 2030. Thus, it is urgent to find an effective treatment for OA. Traditional OA treatments have no disease-modifying effect, while regenerative OA therapies such as autologous chondrocyte implantation show some promise. Nonetheless, current regenerative therapies do not overcome synovial inflammation that suppresses the differentiation of mesenchymal stem cells (MSCs) to chondrocytes and the expression of type II collagen, the major constituent of functional cartilage. We discovered a synergistic combination that overcame synovial inflammation to form type II collagen-producing chondrocytes. The combination consists of peroxisome proliferator-activated receptor (PPAR) δ agonist, human bone marrow (hBM)-derived MSCs, and hyaluronic acid (HA) gel. Interestingly, those individual components showed their own strong enhancing effects on chondrogenesis. GW0742, a PPAR-δ agonist, greatly enhanced MSC chondrogenesis and the expression of type II collagen and glycosaminoglycan (GAG) in hBM-MSC-derived chondrocytes. GW0742 also increased the expression of transforming growth factor β that enhances chondrogenesis and suppresses cartilage fibrillation, ossification, and inflammation. HA gel also increased MSC chondrogenesis and GAG production. However, neither GW0742 nor HA gel could enhance the formation of type II collagen-producing chondrocytes from hBM-MSCs within human OA synovial fluid. Our data demonstrated that the combination of hBM-MSCs, PPAR-δ agonist, and HA gel significantly enhanced the formation of type II collagen-producing chondrocytes within OA synovial fluid from 3 different donors. In other words, the novel combination of PPAR-δ agonist, hBM-MSCs, and HA gel can overcome synovial inflammation to form type II collagen cartilage within human OA synovial fluid. This novel articularly injectable formula could improve OA treatment in the future clinical application.

Factors associated with infection following open distal radius fractures.

PubMed

Glueck, Dane A; Charoglu, Constantine P; Lawton, Jeffrey N

2009-09-01

Open fractures are often classified according to a system described by Gustilo and Anderson. However, this system was applied to open long bone fractures, which may not predict the incidence of infection in open metaphyseal fractures of the upper extremity. Other studies have found that wound contamination and systemic illness were the best predictors of infections in open hand fractures. Our study assessed infection in open distal radius fractures and identifies factors that are associated with these infections. We hypothesize that contamination, rather than absolute wound size, is the best predictor of infection associated with open distal radius fractures. A review by CPT code yielded 42 patients with open distal radius fractures between 1997 and 2002 treated at a level one trauma center. Medical records and radiographic follow-up were reviewed to assess the time to irrigation and debridement, the number of debridements in initial treatment period, the method of operative stabilization, the Gustilo and Anderson type of fracture, the Swanson type of fracture, and description of wound contamination. Forty-two patients were followed up for an average of 15 months (range 4 to 68 months). Twenty-four fractures were classified as Gustilo and Anderson type I, ten were type II, and eight were type III, 30 were Swanson type I, and 12 were Swanson type II. Five of the 42 fractures were considered contaminated. Two were exposed to fecal contamination. The others were contaminated with tar, dirt/grass, and gravel, respectively. Three of 42 (7%) fractures developed infections. All three infected cases received a single irrigation and debridement. Two of five contaminated fractures (40%) developed a polymicrobial infection. Both were exposed to fecal contamination and, therefore, considered Swanson type II fractures. They were classified as Gustilo and Anderson type II and IIIB based solely upon the size of the wound. Both required multiple debridements and eventually wrist fusions. The third infection occurred in a Gustilo and Anderson type II and Swanson type I open fracture treated with one debridement and plate fixation. Hardware removal, debridement, and antibiotics resolved the infection. Three contaminated fractures that healed uneventfully received two debridements. Statistical analysis revealed a correlation with infection and contamination (p = 0.0331). The number of initial debridements played a role in infection, but was not statistically significant. No relationship between infection and time to initial irrigation and debridement, method of fixation, Gustilo and Anderson type, or Swanson type was found. We propose that open distal radius fractures behave differently than open long bone fractures. Infection developed in 7% of the distal radius fractures in our study and was significantly associated with wound contamination. We recommend that contamination be included as factor for prognosis in open distal radius fractures. Contaminated fractures should be treated with multiple debridements as part of the initial plan not based upon subsequent development of an infection.

The synergistic effects of shear stress and cyclic hydrostatic pressure modulate chondrogenic induction of human mesenchymal stem cells.

PubMed

Hosseini, Motahare-Sadat; Tafazzoli-Shadpour, Mohammad; Haghighipour, Nooshin; Aghdami, Naser; Goodarzi, Alireza

2015-10-01

In this study, we examined chondrogenic regulation of 2 types of mesenchymal stem cells seeded on the bioengineered substrate in monolayer cultures under mechanically defined conditions to mimic the in vivo microenvironment of chondrocytes within articular cartilage tissues. Human adipose-derived mesenchymal stem cells (ASCs) and bone marrow mesenchymal stem cells (BSCs) were exposed to 0.2 Pa shear stress, 3 MPa cyclic hydrostatic pressure, and combined loading with different sequences on chemically designed medical-grade silicone rubber, while no soluble growth factors were added to the culture medium. The expression levels of chondrogenic-specific genes of SOX9, aggrecan, and type II collagen (Col II) were measured. Results were compared to those of cells treated by biological growth factor. Gene expression patterns were dependent on the loading regime. Moreover, the source of mesenchymal stem cells (adipose or bone marrow) was influential in gene expression. Overall, enhanced expression of chondrogenic markers was found through application of mechanical stimuli. The response was generally found to be significantly promoted when the 2 loading regimes were superimposed. Differentiation of ASCs was shown by a modest increase in gene expression profiles. In general, BSCs expressed higher levels of chondrogenic gene expression than ASCs after 3 weeks. A greater effect on Col II and SOX9 mRNA expression was observed when combined loadings were applied. Results may be applied in determining the proper loading sequence for obtaining functional target cells in cartilage engineering applications.

[Research of repairing rabbit knee joint cartilage defect by compound material of fibrin glue and decalcified bone matrix (DBM) and chondrocytes].

PubMed

He, Jie; Yang, Xiang; Yue, Peng-ju; Wang, Guan-yu; Guo, Ting; Zhao, Jian-ning

2009-07-01

To investigate the feasibility and effectivity of using compound material of fibrin glue and DBM as scaffolds for cartilage tissue engineering. Chondrocytes isolated from articular cartilage were seeded into prepared scaffolds, after incubation for 4 weeks in vitro. Chondrocytes and fibrin glue and DBM constructs were implanted in the joint cave of rabbit. The specimens were excised at the 4th, 8th, 12th week, examined grossly analyzed by haematoxylin cosine, toluidine blues staining and type II collagen immunohistochemistry reaction. Wakitani score was counted to evaluate the repairing effect. Grossly analysis showed some ivory tissue filled the caves after 4 weeks and the caves were full filled with smooth surface after 12 weeks. The microscope showed a good deal of chondrocytes appeared after 8 weeks and more type II collagen than 4 weeks. Twelve weeks later, cartilage lacuna could be observed. The cells arrangement and the amount of type II collagen both showed the same as the natural one. Complicated material of fibrin glue and DBM as scaffolds can be used as scaffolds for cartilage tissue engineering.

Transforming growth factor-beta1 promotes articular cartilage repair through canonical Smad and Hippo pathways in bone mesenchymal stem cells.

PubMed

Ying, Jun; Wang, Pinger; Zhang, Shanxing; Xu, Taotao; Zhang, Lei; Dong, Rui; Xu, Shibing; Tong, Peijian; Wu, Chengliang; Jin, Hongting

2018-01-01

Transforming growth factor-β1 (TGF-β1) is a chondrogenic factor and has been reported to be able to enhance chondrocyte differentiation from bone marrow mesenchymal stem cells (BMSCs). Here we investigate the molecular mechanism through which TGF-β1 chronically promotes the repair of cartilage defect and inhibit chondrocyte hypertrophy. Animal models of full thickness cartilage defects were divided into three groups: model group, BMSCs group (treated with BMSCs/calcium alginate gel) and BMSCs+TGF-β1 group (treated with Lentivirus-TGF-β1-EGFP transduced BMSCs/calcium alginate gel). 4 and 8weeks after treatment, macroscopic observation, histopathological study and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were done to analyze phenotypes of the animals. BMSCs were transduced with Lentivirus-TGF-β1-EGFP in vitro and Western blot analysis was performed. We found that TGF-β1-expressiing BMSCs improved the repair of the cartilage defect. The impaired cartilage contained higher amount of GAG and type II collagen and was integrated to the surrounding normal cartilage and higher content of GAG and type II collagen. The major events include increased expression of type II collagen following Smad2/3 phosphorylation, and inhibition of cartilage hypertrophy by increasing Yes-associated protein-1 (YAP-1) and inhibiting Runx2 and Col10 after the completion of chondrogenic differentiation. We conclude that TGF-β1 is beneficial to chondrogenic differentiation of BMSCs via canonical Smad pathway to promote early-repairing of cartilage defect. Furthermore, TGF-β1 inhibits chondrocyte hypertrophy by decreasing hypertrophy marker gene expression via Hippo signaling. Long-term rational use of TGF-β1 may be an alternative approach in clinic for cartilage repair and regeneration. Copyright © 2017. Published by Elsevier Inc.

Recombinant human type II collagen hydrogel provides a xeno-free 3D micro-environment for chondrogenesis of human bone marrow-derived mesenchymal stromal cells.

PubMed

Muhonen, Virpi; Narcisi, Roberto; Nystedt, Johanna; Korhonen, Matti; van Osch, Gerjo J V M; Kiviranta, Ilkka

2017-03-01

Recombinant human type II collagen (rhCII) hydrogel was tested as a xeno-free micro-environment for the chondrogenesis of human bone marrow-derived mesenchymal stromal cells (BM-MSCs). The rhCII hydrogels were seeded with BM-MSCs and cultured in a xeno-free chondro-inductive medium for 14, 28 and 84 days. High-density pellet cultures served as controls. The samples were subjected to biochemical, histological and gene expression analyses. Although the cells deposited glycosaminoglycans into the extracellular space significantly more slowly in the rhCII hydrogels compared to the high-density pellets, a similar potential of matrix deposition was reached by the end of the 84-day culture. At day 28 of culture, the gene expression level for cartilage marker genes (i.e. genes encoding for Sox9 transcription factor, Collagen type II and Aggrecan) were considerably lower in the rhCII hydrogels than in the high-density pellets, but at the end of the 84-day culture period, all the cartilage marker genes analysed were expressed at a similar level. Interestingly, the expression of the matrix metallopeptidases (MMP)-13, MMP-14 and MMP-8, i.e. extracellular collagen network-degrading enzymes, were transiently upregulated in the rhCII hydrogel, indicating active matrix reorganization. This study demonstrated that the rhCII hydrogel functions as a xeno-free platform for BM-MSC chondrogenesis, although the process is delayed. The reversible catabolic reaction evoked by the rhCII hydrogel might be beneficial in graft integration in vivo and pinpoints the need to further explore the use of hydrogels containing recombinant extracellular matrix (ECM) proteins to induce the chondrogenesis of MSCs. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Thermal evaluation by infrared measurement of implant site preparation between single and gradual drilling in artificial bone blocks of different densities.

PubMed

Möhlhenrich, S C; Abouridouane, M; Heussen, N; Hölzle, F; Klocke, F; Modabber, A

2016-11-01

The aim of this study was to investigate the influence of bone density and drilling protocol on heat generation during implant bed preparation. Ten single and 10 gradual implant sites with diameters of 2.8, 3.5, and 4.2mm were prepared in four artificial bone blocks (density types I-IV; D1-D4). Drilling was done at constant speed (1500rpm) and with external irrigation (50ml/min); vertical speed was set at 2mm/s. An infrared camera was used for temperature measurements. Significantly higher temperatures for single drilling were found between 2.8-mm drills in D1 (P=0.0014) and D4 (P<0.0001) and between 3.5-mm drills in D3 (P=0.0087) and D4 (P<0.0001), as well as between 4.2-mm drills in D1 (P<0.0001) and D4 (P=0.0014). Low bone density led to a thermal decrease after single drilling and a thermal increase after gradual drilling. Burs with a large diameter always showed a higher temperature generation. In comparisons between 2.8- and 4.2-mm diameters for both single and gradual drills, significant differences (P<0.001) were noted for bone types II, III, and IV. Single drilling could generate more heat than traditional sequential drilling, and bone density, as well as drill diameter, influenced thermal increases. Particularly in lower-density bone, conventional sequential drilling seems to raise the temperature less. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Influence of different abutment diameter of implants on the peri-implant stress in the crestal bone: A three-dimensional finite element analysis--In vitro study.

PubMed

Aradya, Anupama; Kumar, U Krishna; Chowdhary, Ramesh

2016-01-01

The study was designed to evaluate and compare stress distribution in transcortical section of bone with normal abutment and platform switched abutment under vertical and oblique forces in posterior mandible region. A three-dimensional finite element model was designed using ANSYS 13.0 software. The type of bone selection for the model was made of type II mandibular bone, having cortical bone thickness ranging from 0.595 mm to 1.515 mm with the crestal region measuring 1.5 mm surrounding dense trabecular bone. The implant will be modulated at 5 mm restorative platform and tapering down to 4.5 mm wide at the threads, 13 mm long with an abutment 3 mm in height. The models will be designed for two situations: (1) An implant with a 5 mm diameter abutment representing a standard platform in the posterior mandible region. (2) An implant with a 4.5 mm diameter abutment representing platform switching in the posterior mandible region. Force application was performed in both oblique and vertical conditions using 100 N as a representative masticatory force. For oblique loading, a force of 100 N was applied at 15° from the vertical axis. von Mises stress analysis was evaluated. The results of the study showed cortical stress in the conventional and platform switching model under oblique forces were 59.329 MPa and 39.952 MPa, respectively. Cortical stress in the conventional and platform switching model under vertical forces was 13.914 MPa and 12.793 MPa, respectively. Results from this study showed the platform switched abutment led to relative decrease in von Mises stress in transcortical section of bone compared to normal abutment under vertical and oblique forces in posterior mandible region.

Inductive specification and axonal orientation of spinal neurons mediated by divergent bone morphogenetic protein signaling pathways

PubMed Central

2011-01-01

Background Bone morphogenetic protein (BMP)7 evokes both inductive and axon orienting responses in dorsal interneurons (dI neurons) in the developing spinal cord. These events occur sequentially during the development of spinal neurons but in these and other cell types such inductive and acute chemotactic responses occur concurrently, highlighting the requirement for divergent intracellular signaling. Both type I and type II BMP receptor subtypes have been implicated selectively in orienting responses but it remains unclear how, in a given cell, divergence occurs. We have examined the mechanisms by which disparate BMP7 activities are generated in dorsal spinal neurons. Results We show that widely different threshold concentrations of BMP7 are required to elicit the divergent inductive and axon orienting responses. Type I BMP receptor kinase activity is required for activation of pSmad signaling and induction of dI character by BMP7, a high threshold response. In contrast, neither type I BMP receptor kinase activity nor Smad1/5/8 phosphorylation is involved in the low threshold orienting responses of dI axons to BMP7. Instead, BMP7-evoked axonal repulsion and growth cone collapse are dependent on phosphoinositide-3-kinase (PI3K) activation, plausibly through type II receptor signaling. BMP7 stimulates PI3K-dependent signaling in dI neurons. BMP6, which evokes neural induction but does not have orienting activity, activates Smad signaling but does not stimulate PI3K. Conclusions Divergent signaling through pSmad-dependent and PI3K-dependent (Smad-independent) mechanisms mediates the inductive and orienting responses of dI neurons to BMP7. A model is proposed whereby selective engagement of BMP receptor subunits underlies choice of signaling pathway. PMID:22085733

21 CFR 888.3027 - Polymethylmethacrylate (PMMA) bone cement.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Polymethylmethacrylate (PMMA) bone cement. 888... Polymethylmethacrylate (PMMA) bone cement. (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a device... metallic prosthetic implants to living bone. (b) Classification. Class II (special controls). The special...

21 CFR 888.3027 - Polymethylmethacrylate (PMMA) bone cement.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Polymethylmethacrylate (PMMA) bone cement. 888... Polymethylmethacrylate (PMMA) bone cement. (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a device... metallic prosthetic implants to living bone. (b) Classification. Class II (special controls). The special...

21 CFR 888.3027 - Polymethylmethacrylate (PMMA) bone cement.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Polymethylmethacrylate (PMMA) bone cement. 888... Polymethylmethacrylate (PMMA) bone cement. (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a device... metallic prosthetic implants to living bone. (b) Classification. Class II (special controls). The special...

21 CFR 888.3027 - Polymethylmethacrylate (PMMA) bone cement.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Polymethylmethacrylate (PMMA) bone cement. 888... Polymethylmethacrylate (PMMA) bone cement. (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a device... metallic prosthetic implants to living bone. (b) Classification. Class II (special controls). The special...

21 CFR 888.3027 - Polymethylmethacrylate (PMMA) bone cement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Polymethylmethacrylate (PMMA) bone cement. 888... Polymethylmethacrylate (PMMA) bone cement. (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a device... metallic prosthetic implants to living bone. (b) Classification. Class II (special controls). The special...

Comparative ex vivo evaluation of two electronic percussive testing devices measuring the stability of dental implants.

PubMed

Geckili, Onur; Bilhan, Hakan; Cilingir, Altug; Bilmenoglu, Caglar; Ates, Gokcen; Urgun, Aliye Ceren; Bural, Canan

2014-12-01

A comparative ex vivo study was performed to determine electronic percussive test values (PTVs) measured by cabled and wireless electronic percussive testing (EPT) devices and to evaluate the intra- and interobserver reliability of the wireless EPT device. Forty implants were inserted into the vertebrae and forty into the pelvis of a steer, a safe distance apart. The implants were all 4.3 mm wide and 13 mm long, from the same manufacturer. PTV of each implant was measured by four different examiners, using both EPT devices, and compared. Additionally, the intra- and interobserver reliability of the wireless EPT device was evaluated. Statistically significant differences (P <0.05) were observed between PTVs made by the two EPT devices. PTVs measured by the wireless EPT device were significantly higher than the cabled EPT device (P <0.05), indicating lower implant stability. The intraobserver reliability of the wireless EPT device was evaluated as excellent for the measurements in type II bone and good-to-excellent in type IV bone; interobserver reliability was evaluated as fair-to-good in both bone types. The wireless EPT device gives PTVs higher than the cabled EPT device, indicating lower implant stability, and its inter- and intraobserver reliability is good and acceptable.

Sclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing

NASA Astrophysics Data System (ADS)

Spatz, J. M.; Ellman, R.; Cloutier, A. M.; Louis, L.; van Vliet, M.; Dwyer, D.; Stolina, M.; Ke, H. Z.; Bouxsein, M. L.

2017-02-01

Whereas much is known regarding the musculoskeletal responses to full unloading, little is known about the physiological effects and response to pharmacological agents in partial unloading (e.g. Moon and Mars) environments. To address this, we used a previously developed ground-based model of partial weight-bearing (PWB) that allows chronic exposure to reduced weight-bearing in mice to determine the effects of murine sclerostin antibody (SclAbII) on bone microstructure and strength across different levels of mechanical unloading. We hypothesize that treatment with SclAbII would improve bone mass, microarchitecture and strength in all loading conditions, but that there would be a greater skeletal response in the normally loaded mice than in partially unloaded mice suggesting the importance of combined countermeasures for exploration-class long duration spaceflight missions. Eleven-week-old female mice were assigned to one of four loading groups: normal weight-bearing controls (CON) or weight-bearing at 20% (PWB20), 40% (PWB40) or 70% (PWB70) of normal. Mice in each group received either SclAbII (25 mg/kg) or vehicle (VEH) via twice weekly subcutaneous injection for 3 weeks. In partially-unloaded VEH-treated groups, leg BMD decreased -5 to -10% in a load-dependent manner. SclAbII treatment completely inhibited bone deterioration due to PWB, with bone properties in SclAbII-treated groups being equal to or greater than those of CON, VEH-treated mice. SclAbII treatment increased leg BMD from +14 to +18% in the PWB groups and 30 ± 3% in CON (p < 0.0001 for all). Trabecular bone volume, assessed by μCT at the distal femur, was lower in all partially unloaded VEH-treated groups vs. CON-VEH (p < 0.05), and was 2-3 fold higher in SclAbII-treated groups (p < 0.001). Midshaft femoral strength was also significantly higher in SclAbII vs. VEH-groups in all-loading conditions. These results suggest that greater weight bearing leads to greater benefits of SclAbII on bone mass, particularly in the trabecular compartment. Altogether, these results demonstrate the efficacy of sclerostin antibody therapy in preventing astronaut bone loss during terrestrial solar system exploration.

Sclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing.

PubMed

Spatz, J M; Ellman, R; Cloutier, A M; Louis, L; van Vliet, M; Dwyer, D; Stolina, M; Ke, H Z; Bouxsein, M L

2017-02-01

Whereas much is known regarding the musculoskeletal responses to full unloading, little is known about the physiological effects and response to pharmacological agents in partial unloading (e.g. Moon and Mars) environments. To address this, we used a previously developed ground-based model of partial weight-bearing (PWB) that allows chronic exposure to reduced weight-bearing in mice to determine the effects of murine sclerostin antibody (SclAbII) on bone microstructure and strength across different levels of mechanical unloading. We hypothesize that treatment with SclAbII would improve bone mass, microarchitecture and strength in all loading conditions, but that there would be a greater skeletal response in the normally loaded mice than in partially unloaded mice suggesting the importance of combined countermeasures for exploration-class long duration spaceflight missions. Eleven-week-old female mice were assigned to one of four loading groups: normal weight-bearing controls (CON) or weight-bearing at 20% (PWB20), 40% (PWB40) or 70% (PWB70) of normal. Mice in each group received either SclAbII (25mg/kg) or vehicle (VEH) via twice weekly subcutaneous injection for 3 weeks. In partially-unloaded VEH-treated groups, leg BMD decreased -5 to -10% in a load-dependent manner. SclAbII treatment completely inhibited bone deterioration due to PWB, with bone properties in SclAbII-treated groups being equal to or greater than those of CON, VEH-treated mice. SclAbII treatment increased leg BMD from +14 to +18% in the PWB groups and 30 ± 3% in CON (p< 0.0001 for all). Trabecular bone volume, assessed by μCT at the distal femur, was lower in all partially unloaded VEH-treated groups vs. CON-VEH (p< 0.05), and was 2-3 fold higher in SclAbII-treated groups (p< 0.001). Midshaft femoral strength was also significantly higher in SclAbII vs. VEH-groups in all-loading conditions. These results suggest that greater weight bearing leads to greater benefits of SclAbII on bone mass, particularly in the trabecular compartment. Altogether, these results demonstrate the efficacy of sclerostin antibody therapy in preventing astronaut bone loss during terrestrial solar system exploration. Copyright © 2017 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Peripheral vestibular pathology in Mondini dysplasia.

PubMed

Kaya, Serdar; Hızlı, Ömer; Kaya, Fatıma Kübra; Monsanto, Rafael DaCosta; Paparella, Michael M; Cureoglu, Sebahattin

2017-01-01

In this study, our objective was to histopathologically analyze the peripheral vestibular system in patients with Mondini dysplasia. Comparative human temporal bone study. We assessed the sensory epithelium of the human vestibular system with a focus on the number of type I and type II hair cells, as well as the total number of hair cells. We compared those numbers in our Mondini dysplasia group versus our control group. The loss of type I and type II hair cells in the cristae of the superior, lateral, and posterior semicircular canals, as well as in the saccular and utricular macula, was significantly higher in our Mondini dysplasia group than in our control group. The total number of hair cells significantly decreased in the cristae of the superior, lateral, and posterior semicircular canals, as well as in the saccular and utricular macula, in our Mondini dysplasia group. Loss of vestibular hair cells can lead to vestibular dysfunction in patients with Mondini dysplasia. NA Laryngoscope, 127:206-209, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Levels of Evidence in Orthopaedic Trauma Literature.

PubMed

Scheschuk, Joseph P; Mostello, Andrew J; Lombardi, Nicholas J; Maltenfort, Mitchell G; Freedman, Kevin B; Tjoumakaris, Fotios P

2016-07-01

To review and critically assess trends observed regarding the levels of evidence in published articles in orthopaedic traumatology literature. The Journal of Orthopaedic Trauma, Journal of Bone and Joint Surgery-American, and Clinical Orthopaedics and Related Research. All articles from the years 1998, 2003, 2008, and 2013 in The Journal of Orthopaedic Trauma (JOT) and orthopaedic trauma-related articles from The Journal of Bone and Joint Surgery-American (JBJS-A) and Clinical Orthopaedics and Related Research (CORR) were analyzed. Articles were categorized by type and ranked for level of evidence according to guidelines from the Centre for Evidence-Based Medicine. Study type and standardized level of evidence were determined for each article. Articles were subcategorized as high-level evidence (I, II), moderate-level evidence (III), and low-level evidence (IV, V). During the study period, Journal of Bone and Joint Surgery-American reduced its low-level studies from 80% to 40% (P = 0.00015), Clinical Orthopaedics and Related Research decreased its low-level studies from 70% to 27%, and Journal of Orthopaedic Trauma decreased its low-level studies from 78% to 45%. Level IV and V therapeutic, prognostic, and diagnostic studies demonstrated significant decreases during the study period (P = 0.0046, P < 0.0001, P = 0.026). The percentage of high-level studies increased from 13% to 19%; however, this was not significant (P = 0.42). There was a trend showing an increase in level I and II studies for therapeutic, prognostic, and diagnostic studies (P = 0.06). There has been a statistically significant decrease in lower level of evidence studies published in the orthopaedic traumatology literature over the past 15 years.

Isolation and characterization of multipotent human periodontal ligament stem cells.

PubMed

Gay, I C; Chen, S; MacDougall, M

2007-08-01

Periodontal ligament (PDL) repair is thought to involve mesenchymal progenitor cells capable of forming fibroblasts, osteoblasts and cementoblasts. However, full characterization of PDL stem cell (SC) populations has not been achieved. To isolate and characterize PDLSC and assess their capability to differentiate into bone, cartilage and adipose tissue. Human PDL cells were stained for STRO-1, FACS sorted and expanded in culture. Human bone marrow SC (BMSC) served as a positive control. PDLSC and BMSC were cultured using standard conditions conducive for osteogenic, chondrogenic and adipogenic differentiation. Osteogenic induction was assayed using alizarine red S staining and expression of alkaline phosphatase (ALP) and bone sialoprotein (BSP). Adipogenic induction was assayed using Oil Red O staining and the expression of PPAR gamma 2 (early) and LPL (late) adipogenic markers. Chondrogenic induction was assayed by collagen type II expression and toluidine blue staining. Human PDL tissue contains about 27% STRO-1 positive cells with 3% strongly positive. In osteogenic cultures ALP was observed by day-7 in BMSC and day-14 in PDLSC. BSP expression was detectable by day-7; with more intense staining in PDLSC cultures. In adipogenic cultures both cell populations showed positive Oil Red O staining by day-25 with PPAR gamma 2 and LPL expression. By day-21, both BMSC and PDLSC chondrogenic induced cultures expressed collagen type II and glycosaminoglycans. The PDL contains SC that have the potential to differentiate into osteoblasts, chondrocytes and adipocytes, comparable with previously characterized BMSC. This adult PDLSC population can be utilized for potential therapeutic procedures related to PDL regeneration.

Adsorption/reduction of Hg(II) and Pb(II) from aqueous solutions by using bone ash/nZVI composite: effects of aging time, Fe loading quantity and co-existing ions.

PubMed

Gil, Antonio; Amiri, Mohammad Javad; Abedi-Koupai, Jahangir; Eslamian, Saeid

2018-01-01

In this research, a versatile and highly efficient method for the stabilization of nanoscale zerovalent iron particles (nZVI) on the surface of ostrich bone ash (OBA) was presented as a novel inorganic adsorbent (OBA/nZVI) for the removal of Hg(II) and Pb(II) ions from aqueous solutions, even after 1 year of storage under room conditions. The removal behavior of the OBA/nZVI was assessed as a function of the initial pH, contact time, initial pollutants concentration, temperature, amount of adsorbent, effect of competitive metal ions, and ionic strength. The synthesized adsorbent was characterized by several techniques including N 2 adsorption at - 196 °C, FT-IR spectroscopy, scanning electron microscopy, X-ray diffraction, and zeta potential. The results confirmed that the OBA is a good candidate as support of nZVI. The maxima adsorption capacity for Hg(II) and Pb(II) ions found from experimental results were 170 and 160 mg g -1 , when the loading quantities of Fe were 20%. The equilibrium sorption data obeyed a Langmuir-Freundlich isotherm type model. The kinetic data of the adsorption followed the mechanism of the pseudo-second-order model. The thermodynamic experiments indicated that the removal of metal ions were feasible, endothermic, and spontaneous. It can be found that fresh and aged OBA/nZVI maintained its usability even after five cycles in the order: fresh (OBA/nZVI)-Hg(II) > fresh (OBA/nZVI)-Pb(II) > aged (OBA/nZVI)-Hg(II) > aged (OBA/nZVI)-Pb(II), which indicate that OBA/nZVI can be regenerated as adsorbent. The existence of Fe in the OBA/nZVI was proved by SEM-EDX results and X-ray diffraction analysis also confirmed adsorption/reduction of some of the Hg(II) to Hg 0 and Pb(II) to Pb 0 .

PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis.

PubMed

Orth, P; Cucchiarini, M; Wagenpfeil, S; Menger, M D; Madry, H

2014-06-01

To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit in vivo. Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P < 0.05). Moreover, PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P < 0.03). These early osteoarthritic changes correlated with and were ascribed to the increased thickness of the calcified cartilage layer (P = 0.026) and enhanced mineral density of the subarticular spongiosa (P = 0.001). Modifications of the subarticular spongiosa by PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effect of the masseter muscle injection of botulinum toxin A on the mandibular bone growth of developmental rats.

PubMed

Seok, Hyun; Kim, Seong-Gon; Kim, Min-Keun; Jang, Insan; Ahn, Janghoon

2018-12-01

The objective of this study was to evaluate the influence of masticatory muscle injection of botulinum toxin type A (BTX-A) on the growth of the mandibular bone in vivo. Eleven Sprague-Dawley rats were used, and BTX-A ( n  = 6) or saline ( n  = 5) was injected at 13 days of age. All injections were given to the right masseter muscle, and the BTX-A dose was 0.5 units. All of the rats were euthanized at 60 days of age. The skulls of the rats were separated and fixed with 10% formalin for micro-computed tomography (micro-CT) analysis. The anthropometric analysis found that the ramus heights and bigonial widths of the BTX-A-injected group were significantly smaller than those of the saline-injected group ( P  < 0.05), and the mandibular plane angle of the BTX-A-injected group was significantly greater than in the saline-injected group ( P  < 0.001). In the BTX-A-injected group, the ramus heights II and III and the mandibular plane angles I and II showed significant differences between the injected and non-injected sides ( P  < 0.05). The BTX-A-injected side of the mandible in the masseter group showed significantly lower mandibular bone growth compared with the non-injected side. BTX-A injection into the masseter muscle influences mandibular bone growth.

Elastomeric enriched biodegradable polyurethane sponges for critical bone defects: a successful case study reducing donor site morbidity.

PubMed

Lavrador, Catarina; Mascarenhas, Ramiro; Coelho, Paulo; Brites, Cláudia; Pereira, Alfredo; Gogolewski, Sylwester

2016-03-01

Bone substitutes have been a critical issue as the natural source can seldom provide enough bone to support full healing. No bone substitute complies with all necessary functions and characteristics that an autograft does. Polyurethane sponges have been used as a surgical alternative to cancellous bone grafts for critical bone defect donor sites. Critical bone defects were created on the tibial tuberosity and iliac crest using an ovine model. In group I (control-untreated), no bone regeneration was observed in any animal. In group II (defects left empty but covered with a microporous polymeric membrane), the new bone bridged the top ends in all animals. In groups III and IV, bone defects were implanted with polyurethane scaffolds modified with biologically active compounds, and bone regeneration was more efficient than in group II. In groups III and IV there were higher values of bone regeneration specific parameters used for evaluation (P < 0.05) although the comparison between these groups was not possible. The results obtained in this study suggest that biodegradable polyurethane substitutes modified with biologically active substances may offer an alternative to bone graft, reducing donor site morbidity associated with autogenous cancellous bone harvesting.

Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation.

PubMed

Liu, Chang; Rajapakse, Angana G; Riedo, Erwin; Fellay, Benoit; Bernhard, Marie-Claire; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

2016-02-05

Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II(-/-) mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-α and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II(-/-) mice liver. Moreover, release of TNF-α and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II(-/-) mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II(-/-)-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-α and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-α and IL-6 in obesity.

Bilateral calcaneal epiphysiolysis in a dog.

PubMed

Font, J; Pèlach, M; Font, C; Cairo, J

2013-01-01

A case of bilateral calcaneal epiphysiolysis in a six-month-old female Dobermann Pinscher is described in this report. The absence of a traumatic event and the clinical, radiographic and histopathological abnormalities led us to the diagnosis of simultaneous bilateral epiphysiolysis of the calcaneus. A tension band and a type II transarticular external fixator were placed. The clinical signs were resolved only temporarily because of the gravity of the bone changes.

Remission of Collagen-Induced Arthritis through Combination Therapy of Microfracture and Transplantation of Thermogel-Encapsulated Bone Marrow Mesenchymal Stem Cells

PubMed Central

Liu, He; Ding, Jianxun; Wang, Jincheng; Wang, Yinan; Yang, Modi; Zhang, Yanbo; Chang, Fei; Chen, Xuesi

2015-01-01

The persistent inflammation of rheumatoid arthritis (RA) always leads to partial synovial hyperplasia and the destruction of articular cartilage. Bone marrow mesenchymal stem cells (BMMSCs) have been proven to possess immunosuppressive effects, and widely explored in the treatment of autoimmune diseases. However, poor inhibitory effect on local inflammatory state and limited capacity of preventing destruction of articular cartilage by systemic BMMSCs transplantation were observed. Herein, toward the classical type II collagen-induced arthritis in rats, the combination treatment of microfracture and in situ transplantation of thermogel-encapsulated BMMSCs was verified to obviously down-regulate the ratio of CD4+ to CD8+ T lymphocytes in peripheral blood. In addition, it resulted in the decreased levels of inflammatory cytokines, such as interleukin-1β, tumor necrosis factor-α and anti-collagen type II antibody, in the serum. Simultaneously, the combination therapy also could inhibit the proliferation of antigen specific lymphocytes and local joint inflammatory condition, and prevent the articular cartilage damage. The results indicated that the treatment programs could effectively stimulate the endogenous and exogenous BMMSCs to exhibit the immunosuppression and cartilage protection capability. This study provided a new therapeutic strategy for autoimmune inflammatory diseases, such as RA. PMID:25774788

[Morphological analysis of alveolar bone of anterior mandible in high-angle skeletal class II and class III malocclusions assessed with cone-beam computed tomography].

PubMed

Ma, J; Jiang, J H

2018-02-18

To evaluate the difference of features of alveolar bone support under lower anterior teeth between high-angle adults with skeletal class II malocclusions and high-angle adults presenting skeletal class III malocclusions by using cone-beam computed tomography (CBCT). Patients who had taken the images of CBCT were selected from the Peking University School and Hospital of Stomatology between October 2015 and August 2017. The CBCT archives from 62 high-angle adult cases without orthodontic treatment were divided into two groups based on their sagittal jaw relationships: skeletal class II and skeletal class III. vertical bone level (VBL), alveolar bone area (ABA), and the width of alveolar bone were measured respectively at the 2 mm, 4 mm, 6 mm below the cemento-enamel junction (CEJ) level and at the apical level. After that, independent samples t-tests were conducted for statistical comparisons. The ABA of the mandibular alveolar bone in the area of lower anterior teeth was significantly thinner in the patients of skeletal class III than those of skeletal class II, especially in terms of the apical ABA, total ABA on the labial and lingual sides and the ABA at 6 mm below CEJ level on the lingual side (P<0.05). The thickness of the alveolar bone of mandibular anterior teeth was significantly thinner in the subjects of skeletal class III than those of skeletal class II, especially regarding the apical level on the labial and lingual side and at the level of 4 mm, 6 mm below CEJ level on the lingual side (P<0.05). The ABA and the thickness of the alveolar bone of mandibular anterior teeth were significantly thinner in the group of skeletal class III adult patients with high-angle when compared with the sample of high-angle skeletal class II adult cases. We recommend orthodontists to be more cautious in treatment of high-angle skeletal class III patients, especially pay attention to control the torque of lower anterior teeth during forward and backward movement, in case that the apical root might be absorbed or fenestration happen in the area of lower anterior teeth.

Repair of articular cartilage and subchondral defects in rabbit knee joints with a polyvinyl alcohol/nano-hydroxyapatite/polyamide 66 biological composite material.

PubMed

Guo, Tao; Tian, Xiaobin; Li, Bo; Yang, Tianfu; Li, Yubao

2017-11-15

This study sought to prepare a new PVA/n-HA/PA66 composite to investigate the repair of articular cartilage and subchondral defects in rabbit knee joints. A 5 × 5 × 5 mm-sized defect was created in the patellofemoral joints of 72 healthy adult New Zealand rabbits. The rabbits were then randomly divided into three groups (n = 24): PVA/n-HA+PA66 group, polyvinyl alcohol (PVA) group, and control (untreated) group. Cylindrical PVA/n-HA+PA66, 5 × 5 mm, comprised an upper PVA layer and a lower n-HA+PA66 layer. Macroscopic and histological evaluations were performed at 4, 8, 12, and 24 weeks, postoperatively. Type II collagen was measured by immunohistochemical staining. The implant/cartilage and bone interfaces were observed by scanning electron microscopy. At 24 weeks postoperatively, the lower PVA/n-HA+PA66 layer became surrounded by cartilage, with no obvious degeneration. In the PVA group, an enlarged space was observed between the implant and the host tissue that had undergone degeneration. In the control group, the articular cartilage had become calcified. In the PVA/n-HA+PA66 group, positive type II collagen staining was observed between the composite and the surrounding cartilage and on the implant surface. In the PVA group, positive staining was slightly increased between the PVA and the surrounding cartilage, but reduced on the PVA surface. In the control group, reduced staining was observed throughout. Scanning electron microscopy showed increased bone tissue in the lower n-HA+PA66 layer that was in close approximation with the upper PVA layer of the composite. In the PVA group, the bone tissue around the material had receded, and in the control group, the defect was filled with bone tissue, while the superior aspect of the defect was filled with disordered, fibrous tissue. The diphase biological composite material PVA/n-HA+PA66 exhibits good histocompatibility and offers a satisfactory substitute for articular cartilage and subchondral bone.

A Primary Investigation on Serum CTX-II Changes in Patients Infected with Brucellosis in Qinghai Plateau, China.

PubMed

Zhao, Zhi Jun; Li, Qiang; Zhou, Xin; Ma, Li; Xu, Li Qing; Yang, Pei Zhen; Meng, Xian Ya; Yu, Hui Zhen; Xu, Xiao Qing; Cao, Jian Ying

2016-03-01

Brucellosis is one of the most widespread zoonotic diseases, with the most frequent complication being osteoarticular changes. The aim of this study was to assess the changes of C-terminal telopeptide of type II collagen (CTX-II) in patients infected with brucellosis. A total of 84 brucellosis patients and 43 volunteers were selected and divided into brucellosis vs. control groups. Serum samples were subjected to serological tests for brucellosis, and CTX-II levels in all samples were measured simultaneously with ELISA. The results showed that serum CTX-II levels in human brucellosis were higher than those of healthy controls, without a statistically significant difference, but serum CTX-II levels in male patients were significantly higher than those of female patients (P<0.05). This finding could indicate the biological changes in the cartilage and bone in human brucellosis. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Conditional deletion of Pkd1 in osteocytes disrupts skeletal mechanosensing in mice

PubMed Central

Xiao, Zhousheng; Dallas, Mark; Qiu, Ni; Nicolella, Daniel; Cao, Li; Johnson, Mark; Bonewald, Lynda; Quarles, L. Darryl

2011-01-01

We investigated whether polycystin-1 is a bone mechanosensor. We conditionally deleted Pkd1 in mature osteoblasts/osteocytes by crossing Dmp1-Cre with Pkd1flox/m1Bei mice, in which the m1Bei allele is nonfunctional. We assessed in wild-type and Pkd1-deficient mice the response to mechanical loading in vivo by ulna loading and ex vivo by measuring the response of isolated osteoblasts to fluid shear stress. We found that conditional Pkd1 heterozygotes (Dmp1-Cre;Pkd1flox/+) and null mice (Pkd1Dmp1-cKO) exhibited a ∼40 and ∼90% decrease, respectively, in functional Pkd1 transcripts in bone. Femoral bone mineral density (12 vs. 27%), trabecular bone volume (32 vs. 48%), and cortical thickness (6 vs. 17%) were reduced proportionate to the reduction of Pkd1 gene dose, as were mineral apposition rate (MAR) and expression of Runx2-II, Osteocalcin, Dmp1, and Phex. Anabolic load-induced periosteal lamellar MAR (0.58±0.14; Pkd1Dmp1-cKO vs. 1.68±0.34 μm/d; control) and increases in Cox-2, c-Jun, Wnt10b, Axin2, and Runx2-II gene expression were significantly attenuated in Pkd1Dmp1-cKO mice compared with controls. Application of fluid shear stress to immortalized osteoblasts from Pkd1null/null and Pkd1m1Bei/m1Bei-derived osteoblasts failed to elicit the increments in cytosolic calcium observed in wild-type controls. These data indicate that polycystin-1 is essential for the anabolic response to skeletal loading in osteoblasts/osteocytes.—Xiao, Z., Dallas, M., Qiu, N., Nicolella, D., Cao, L., Johnson, M., Bonewald, L., Quarles, L. D. Conditional deletion of Pkd1 in osteocytes disrupts skeletal mechanosensing in mice. PMID:21454365

Disentangling Early Stone Age palimpsests: determining the functional independence of hominid- and carnivore-derived portions of archaeofaunas.

PubMed

Egeland, Charles P; Pickering, Travis Rayne; Domínguez-Rodrigo, Manuel; Brain, C K

2004-11-01

Determining the extent to which hominid- and carnivore-derived components of fossil bone palimpsests formed independently of each other can provide valuable information to paleoanthropologists interested in reconstructing the foraging adaptations of hominids. Because stone tool cutmarks, hammerstone percussion marks, and carnivore tooth marks are usually only imparted on bone during nutrient extraction from a carcass, these bone surface modifications are particularly amenable to the types of analyses that might meet this goal. This study compares the percentage of limb bone specimens that preserve evidence of both hominid- and carnivore-imparted bone damage from actualistic control samples and several Plio-Pleistocene archaeofaunas, including new data from Swartkrans Member 3 (South Africa). We argue that this procedure, which elucidates the degree of hominid-carnivore independence in assemblage formation, will allow researchers to extract for focused analyses high integrity components (hominid and carnivore) from presumably low integrity sites. Comparisons suggest that the hominid- and carnivore-derived components from sites in Olduvai Gorge Bed II (Tanzania), the ST Site Complex at Peninj (Tanzania), and Swartkrans Member 3 formed largely independent of each other, while data from the FLK 22 Zinjanthropus (FLK Zinj) site (Olduvai Gorge Bed I) indicate significant interdependence in assemblage formation. This contrast suggests that some Early Stone Age assemblages (e.g., the Olduvai Gorge Bed II sites, the Peninj ST Site Complex, and Swartkrans Member 3) are probably more useful than others (e.g., FLK Zinj) for assessing the maximal carcass-acquiring abilities of early hominids; in such assemblages as those in the former set, sole hominid-contribution is more confidently discerned and isolated for analysis than in assemblages such as FLK Zinj.

A new technique in the surgical treatment of Hangman's fractures: Neurospinal Academy (NSA) technique

PubMed Central

Dalbayrak, Sedat; Yaman, Onur; Yılmaz, Mesut

2013-01-01

Context: Treatment of Hangman's fractures is still controversial. Hangman's fractures Type II and IIA are usually treated with surgical procedures. Aim: This study aims at describing the Neurospinal Academy (NSA) technique as an attempt to achieve an approximation of the fracture line to the axis body, which may be used for Type II and IIA patients with severe displacement and angulation. Settings and Design: NSA technique both pars or pedicle screws are placed bicortically to ensure that anterior surface of C2 vertebral body will be crossed 1-2 mm. A rod is prepared in suitable length and curve to connect the two screws. For placing the rod, sufficient amount of bone is resected from the C2 spinous process. C2 vertebral body is pulled back by means of the screws that crossed the anterior surface of C2 vertebral body. Materials and Methods: Hangman II and IIA patient are treated with NSA technique. Result: Angulated and tilted C2 vertebral body was pulled back and approximated to posterior elements. Conclusions: In Hangman's fractures Type II and IIA with severe vertebral body and pedicle displacement, NSA technique is an effective and reliable treatment alternative for the approximation of posterior elements to the C2 vertebral body, which is tilted, angulated, and dislocated. PMID:24744563

A new technique in the surgical treatment of Hangman's fractures: Neurospinal Academy (NSA) technique.

PubMed

Dalbayrak, Sedat; Yaman, Onur; Yılmaz, Mesut

2013-07-01

Treatment of Hangman's fractures is still controversial. Hangman's fractures Type II and IIA are usually treated with surgical procedures. This study aims at describing the Neurospinal Academy (NSA) technique as an attempt to achieve an approximation of the fracture line to the axis body, which may be used for Type II and IIA patients with severe displacement and angulation. NSA technique both pars or pedicle screws are placed bicortically to ensure that anterior surface of C2 vertebral body will be crossed 1-2 mm. A rod is prepared in suitable length and curve to connect the two screws. For placing the rod, sufficient amount of bone is resected from the C2 spinous process. C2 vertebral body is pulled back by means of the screws that crossed the anterior surface of C2 vertebral body. Hangman II and IIA patient are treated with NSA technique. Angulated and tilted C2 vertebral body was pulled back and approximated to posterior elements. In Hangman's fractures Type II and IIA with severe vertebral body and pedicle displacement, NSA technique is an effective and reliable treatment alternative for the approximation of posterior elements to the C2 vertebral body, which is tilted, angulated, and dislocated.

Bone x-ray

MedlinePlus

... different views of the bone may be uncomfortable. Why the Test is Performed A bone x-ray ... neoplasia (MEN) II Multiple myeloma Osgood-Schlatter disease Osteogenesis imperfecta Osteomalacia Paget's disease Primary hyperparathyroidism Rickets Risks There ...

21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Resorbable calcium salt bone void filler device... salt bone void filler device. (a) Identification. A resorbable calcium salt bone void filler device is... entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for...

21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Resorbable calcium salt bone void filler device... salt bone void filler device. (a) Identification. A resorbable calcium salt bone void filler device is... entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for...

21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Resorbable calcium salt bone void filler device... salt bone void filler device. (a) Identification. A resorbable calcium salt bone void filler device is... entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for...

21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Resorbable calcium salt bone void filler device... salt bone void filler device. (a) Identification. A resorbable calcium salt bone void filler device is... entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for...

21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Resorbable calcium salt bone void filler device... salt bone void filler device. (a) Identification. A resorbable calcium salt bone void filler device is... entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for...

Novel antiosteoclastogenic activity of phloretin antagonizing RANKL-induced osteoclast differentiation of murine macrophages.

PubMed

Kim, Jung-Lye; Kang, Min-Kyung; Gong, Ju-Hyun; Park, Sin-Hye; Han, Seon-Young; Kang, Young-Hee

2012-08-01

Bone-remodeling imbalance resulting in more bone resorption than bone formation is known to cause skeletal diseases such as osteoporosis. Phloretin, a natural dihydrochalcone compound largely present in apple peels, possesses antiphotoaging, and antiinflammatory activity. Phloretin inhibited receptor activator of NF-κB ligand (RANKL)-induced formation of multinucleated osteoclasts and diminished bone resorption area produced during the osteoclast differentiation process. It was also found that ≥ 10 μM phloretin reduced RANKL-enhanced tartrate-resistance acid phosphatase activity and matrix metalloproteinase-9 secretion in a dose-dependent manner. The phloretin treatment retarded RANKL-induced expression of carbonic anhydrase II, vacuolar-type H(+) -ATPase D2 and β3 integrin, all involved in the bone resorption. Furthermore, submicromolar phloretin diminished the expression and secretion of cathepsin K elevated by RANKL, being concurrent with inhibition of TRAF6 induction and NF-κB activation. RANKL-induced activation of nuclear factor of activated T cells c1 (NFATc1) and microphthalmia-associated transcription factor was also suppressed by phloretin. These results demonstrate that the inhibition of osteoclast differentiation and bone resorption by phloretin entail a disturbance of TRAF6-NFATc1-NF-κB pathway triggered by RANKL. Therefore, phloretin may be a potential therapeutic agent targeting osteoclast differentiation and bone resorption in skeletal diseases such as osteoporosis. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessment of the correlation between insertion torque and resonance frequency analysis of implants placed in bone tissue of different densities.

PubMed

Filho, Luiz Carlos Magno; Cirano, Fabiano Ribeiro; Hayashi, Fernando; Feng, Hsu Shao; Conte, Alexandre; Dib, Luciano Lauria; Casati, Marcio Zaffalon

2014-06-01

The primary stability of dental implants is fundamental for osseointegration. Therefore, this study aimed to assess the correlation between insertion torque (IT) and resonance frequency analysis (RFA) of implants placed in mandibles and maxillas of different bone densities. Eighty dental implants were placed in maxillas and mandibles, and IT and the implant stability quotient (ISQ) were measured at the time of implant insertion. Bone density was assessed subjectively by the Lekholm and Zarb index. The type I and II densities were grouped together (group A)as were the type III and IV densities (group B). The IT in group A was higher (Student t test, P = .0013) than in group B (46.27 ± 18.51 Ncm, 33.62 ± 14.74 Ncm, respectively). The implants placed in group A showed higher ISQ (Student t test, P = .0004) than those placed in group B (70.09 ± 7.50, 63.66 ± 8.00, respectively). A significant correlation between IT and the ISQ value was observed for group A (Pearson correlation test; r = 0.35; P = .0213) and for group B (r = 0.37; P = .0224). Within the limitations of this study, it was possible to conclude that there is a correlation between IT and RFA of implants placed in mandibles and maxillas of different bone densities.

Bone turnover biomarkers in obese postmenopausal Saudi women with type-II diabetes mellitus.

PubMed

Alselami, Nada M; Noureldeen, Amani F H; Al-Ghamdi, Maryam A; Khan, Jalaluddin A; Moselhy, Said S

2015-03-01

There is a high prevalence of diabetes mellitus type-2 (T2DM) and osteoporosis are problems worldwide. In this study, we evaluated the correlation between T2DM and bone turnover in diabetic obese postmenopausal Saudi women. The present study included total of 65 T2-DM obese postmenopausal Saudi women, (36 uncontrolled, 29 controlled). The following serum biochemical parameters were evaluated [fasting blood glucose (FBG), total calcium (Ca), phosphorus (Pi), parathyroid hormone (PTH), 1,25-(OH)2 Vitamin D3, osteocalcin (OC), procollagen (PICP) and cathepsin k (Cath K)]. Serum OC levels were significantly decreased in diabetic obese postmenopausal group compared to their respective healthy group (P < 0.004). PICP and Cath K were significantly elevated in diabetic postmenopausal group compared to the healthy group (P < 0.024 & 0.001). A significant elevation in 1,25(OH)2 Vitamin D3, Ca and Pi levels in diabetic obese postmenopausal patients group compared to the healthy group. However, a non-significant changes was observed in serum PTH level between different groups. In this study, the changes in the biochemical parameters and bone turnover markers in obese women are strong risk factors for diabetes development that may contribute to osteopenia and osteoporosis. The study showed the strong effect of T2DM on biochemical markers of bone turnover in obese postmenopausal Saudi women.

Interleukin-6 from subchondral bone mesenchymal stem cells contributes to the pathological phenotypes of experimental osteoarthritis

PubMed Central

Wu, Xiaofeng; Cao, Lei; Li, Fan; Ma, Chao; Liu, Guangwang; Wang, Qiugen

2018-01-01

As a main cause of morbidity in the aged population, osteoarthritis (OA) is characterized by cartilage destruction, synovium inflammation, osteophytes, and subchondral bone sclerosis. To date its etiology remains elusive. Recent data highlight an important role of subchondral bone in the onset and progression of OA. Therefore, elucidating the mechanisms underlying abnormal subchondral bone could be of importance in the treatment of OA. Interleukin-6 is a proinflammatory cytokine involved in many physiological and pathological processes. Although in vitro and in vivo studies have indicated that IL-6 is an important cytokine in the physiopathogenesis of OA, its effects on subchondral bone have not been studied in OA animal models. In this study, we aimed to i) investigate the role of IL-6 in the pathological phenotypes of OA subchondral bone MSCs including increase in cell numbers, mineralization disorder and abnormal type I collagen production; ii) explore whether the systemic blockade of IL-6 signaling could alleviate the pathological phenotypes of experimental OA. We found that IL-6 was over-secreted by OA subchondral bone MSCs compared with normal MSCs and IL-6/STAT3 signaling was over-activated in subchondral bone MSCs, which contributed to the pathological phenotypes of OA subchondral bone MSCs. More importantly, systemic inhibition of IL-6/STAT3 signaling with IL-6 antibody or STAT3 inhibitor AG490 decreased the severity of pathological phenotypes of OA subchondral bone MSCs and cartilage lesions in OA. Our findings provide strong evidence for a pivotal role for IL-6 signaling in OA and open up new therapeutic perspectives. PMID:29736207

Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior mandible (Type II bone) in dogs.

PubMed

Wikesjö, Ulf M E; Xiropaidis, Andreas V; Qahash, Mohammed; Lim, Won Hee; Sorensen, Rachel G; Rohrer, Michael D; Wozney, John M; Hall, Jan

2008-11-01

Conventional oral/maxillofacial implants reach osseointegration over several months during which the titanium fixtures interact with alveolar bone. The objective of this study was to determine if adsorbing recombinant human bone morphogenetic protein-2 (rhBMP-2) onto a titanium porous oxide (TPO) implant surface might enhance or accelerate local bone formation and support osseointegration in a large animal oral/maxillofacial orthotopic model. Endosseous implants with a TPO surface were installed into the edentulated posterior mandible in eight adult Hound Labrador mongrel dogs. The implant surface had been adsorbed with rhBMP-2 at 0.2 or 4.0 mg/ml. TPO implants without rhBMP-2 served as control. Treatments were randomized between jaw quadrants. Mucosal flaps were advanced and sutured leaving the implants submerged. Clinical and radiographic evaluations were made immediately post-surgery, at day 10 (suture removal), and week 4 and 8 post-surgery. The animals received fluorescent bone markers at week 3, 4, and at week 8 post-surgery, when they were euthanized for histologic analysis. TPO implants coated with rhBMP-2 exhibited dose-dependent bone remodelling including immediate resorption and formation of implant adjacent bone, and early establishment of clinically relevant osseointegration. The resulting bone-implant contact, although clinically respectable, appeared significantly lower for rhBMP-2-coated implants compared with the control [rhBMP-2 (0.2 mg/ml) 43.3+/-10.8%versus 71.7+/-7.8%, p<0.02; rhBMP-2 (4.0 mg/ml) 35.4+/-10.6%versus 68.2+/-11.0%, p<0.03]. rhBMP-2 adsorbed onto TPO implant surfaces initiates dose-dependent peri-implant bone re-modelling resulting in the formation of normal, physiologic bone and clinically relevant osseointegration within 8 weeks.

Permanence of diced cartilage, bone dust and diced cartilage/bone dust mixture in experimental design in twelve weeks.

PubMed

Islamoglu, Kemal; Dikici, Mustafa Bahadir; Ozgentas, Halil Ege

2006-09-01

Bone dust and diced cartilage are used for contour restoration because their minimal donor site morbidity. The purpose of this study is to investigate permanence of bone dust, diced cartilage and bone dust/diced cartilage mixture in rabbits over 12 weeks. New Zealand white rabbits were used for this study. There were three groups in the study: Group I: 1 mL bone dust. Group II: 1 mL diced cartilage. Group III: 0.5 mL bone dust + 0.5 mL diced cartilage mixture. They were placed into subcutaneous tissue of rabbits and removed 12 weeks later. The mean volumes of groups were 0.23 +/- 0.08 mL in group I, 0.60 +/- 0.12 mL in group II and 0.36 +/- 0.10 mL in group III. The differences between groups were found statistically significant. In conclusion, diced cartilage was found more reliable than bone dust aspect of preserving its volume for a long period in this study.

Reviewing subchondral cartilage surgery: considerations for standardised and outcome predictable cartilage remodelling: a technical note.

PubMed

Benthien, Jan P; Behrens, Peter

2013-11-01

The potential of subchondral mesenchymal stem cell stimulation (MSS) for cartilage repair has led to the widespread use of microfracture as a first line treatment for full thickness articular cartilage defects. Recent focus on the effects of subchondral bone during cartilage injury and repair has expanded the understanding of the strengths and limitations in MSS and opened new pathways for potential improvement. Comparative studies have shown that bone marrow access has positive implications for pluripotential cell recruitment, repair quality and quantity, i.e. deeper channels elicited better cartilage fill, more hyaline cartilage character with higher type II collagen content and lower type I collagen content compared to shallow marrow access. A subchondral needling procedure using standardised and thin subchondral perforations deep into the subarticular bone marrow making the MSS more consistent with the latest developments in subchondral cartilage remodelling is proposed. As this is a novel method clinical studies have been initiated to evaluate the procedure especially compared to microfracturing. However, the first case studies and follow-ups indicate that specific drills facilitate reaching the subchondral bone marrow while the needle size makes perforation of the subchondral bone easier and more predictable. Clinical results of the first group of patients seem to compare well to microfracturing. The authors suggest a new method for a standardised procedure using a new perforating device. Advances in MSS by subchondral bone marrow perforation are discussed. It remains to be determined by clinical studies how this method compares to microfracturing. The subchondral needling offers the surgeon and the investigator a method that facilitates comparison studies because of its defined depth of subchondral penetration and needle size.

Insulin-like growth factor-II regulates bone sialoprotein gene transcription.

PubMed

Choe, Jin; Sasaki, Yoko; Zhou, Liming; Takai, Hideki; Nakayama, Yohei; Ogata, Yorimasa

2016-09-01

Insulin-like growth factor-I and -II (IGF-I and IGF-II) have been found in bone extracts of several different species, and IGF-II is the most abundant growth factor stored in bone. Bone sialoprotein (BSP) is a noncollagenous extracellular matrix glycoprotein associated with mineralized connective tissues. In this study, we have investigated the regulation of BSP transcription by IGF-II in rat osteoblast-like ROS17/2.8 cells. IGF-II (50 ng/ml) increased BSP mRNA and protein levels after 6-h stimulation, and enhanced luciferase activities of the constructs pLUC3 (-116 to +60), pLUC4 (-425 to +60), pLUC5 (-801 to +60) and pLUC6 (-938 to +60). Effects of IGF-II were inhibited by tyrosine kinase, extracellular signal-regulated kinase1/2 and phosphatidylinositol 3-kinase inhibitors, and abrogated by 2-bp mutations in cAMP response element (CRE), FGF2 response element (FRE) and homeodomain protein-binding site (HOX). The results of gel shift assays showed that nuclear proteins binding to CRE, FRE and HOX sites were increased by IGF-II (50 ng/ml) at 3 and 6 h. CREB1, phospho-CREB1, c-Fos and c-Jun antibodies disrupted the formation of the CRE-protein complexes. Dlx5 and Runx2 antibodies disrupted the FRE- and HOX-protein complex formations. These studies therefore demonstrated that IGF-II increased BSP transcription by targeting CRE, FRE and HOX elements in the proximal promoter of the rat BSP gene. Moreover, phospho-CREB1, c-Fos, c-Jun, Dlx5 and Runx2 transcription factors appear to be key regulators of IGF-II effects on BSP transcription.

Generation of a Bone Organ by Human Adipose-Derived Stromal Cells Through Endochondral Ossification.

PubMed

Osinga, Rik; Di Maggio, Nunzia; Todorov, Atanas; Allafi, Nima; Barbero, Andrea; Laurent, Frédéric; Schaefer, Dirk Johannes; Martin, Ivan; Scherberich, Arnaud

2016-08-01

: Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. Unlike bone marrow-derived stromal cells (also known as bone marrow-derived mesenchymal stromal/stem cells), adipose-derived stromal cells (ASC) have so far failed to form a bone organ by ECO. The goal of the present study was to assess whether priming human ASC to a defined stage of chondrogenesis in vitro allows their autonomous ECO upon ectopic implantation. ASC were cultured either as micromass pellets or into collagen sponges in chondrogenic medium containing transforming growth factor-β3 and bone morphogenetic protein-6 for 4 weeks (early hypertrophic templates) or for two additional weeks in medium supplemented with β-glycerophosphate, l-thyroxin, and interleukin1-β to induce hypertrophic maturation (late hypertrophic templates). Constructs were implanted in vivo and analyzed after 8 weeks. In vitro, ASC deposited cartilaginous matrix positive for glycosaminoglycans, type II collagen, and Indian hedgehog. Hypertrophic maturation induced upregulation of type X collagen, bone sialoprotein, and matrix metalloproteinase13 (MMP13). In vivo, both early and late hypertrophic templates underwent cartilage remodeling, as assessed by MMP13- and tartrate-resistant acid phosphatase-positive staining, and developed bone ossicles, including bone marrow elements, although to variable degrees of efficiency. In situ hybridization for human-specific sequences and staining with a human specific anti-CD146 antibody demonstrated the direct contribution of ASC to bone and stromal tissue formation. In conclusion, despite their debated skeletal progenitor nature, human ASC can generate bone organs through ECO when suitably primed in vitro. Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. This study demonstrated that expanded, human adult adipose-derived stromal cells can generate ectopic bone through ECO, as previously reported for bone marrow stromal cells. This system can be used as a model in a variety of settings for mimicking ECO during development, physiology, or pathology (e.g., to investigate the role of BMPs, their receptors, and signaling pathways). The findings have also translational relevance in the field of bone regeneration, which, despite several advances in the domains of materials and surgical techniques, still faces various limitations before being introduced in the routine clinical practice. ©AlphaMed Press.

[The role of Smads and related transcription factors in the signal transduction of bone morphogenetic protein inducing bone formation].

PubMed

Xu, Xiao-liang; Dai, Ke-rong; Tang, Ting-ting

2003-09-01

To clarify the mechanisms of the signal transduction of bone morphogenetic proteins (BMPs) inducing bone formation and to provide theoretical basis for basic and applying research of BMPs. We looked up the literature of the role of Smads and related transcription factors in the signal transduction of BMPs inducing bone formation. The signal transduction processes of BMPs included: 1. BMPs combined with type II and type I receptors; 2. the type I receptor phosphorylated Smads; and 3. Smads entered the cell nucleus, interacted with transcription factors and influenced the transcription of related proteins. Smads could be divided into receptor-regulated Smads (R-Smads: Smad1, Smad2, Smad3, Smad5, Smad8 and Smad9), common-mediator Smad (co-Smad: Smad4), and inhibitory Smads (I-Smads: Smad6 and Smad7). Smad1, Smad5, Smad8, and probable Smad9 were involved in the signal transduction of BMPs. Multiple kinases, such as focal adhesion kinase (FAK), Ras-extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and Akt serine/threonine kinase were related to Smads signal transduction. Smad1 and Smad5 related with transcription factors included core binding factor A1 (CBFA1), smad-interacting protein 1 (SIP1), ornithine decarboxylase antizyme (OAZ), activating protein-1 (AP-1), xenopus ventralizing homeobox protein-2 (Xvent-2), sandostatin (Ski), antiproliferative proteins (Tob), and homeodomain-containing transcriptian factor-8 (Hoxc-8), et al. CBFA1 could interact with Smad1, Smad2, Smad3, and Smad5, so it was involved in TGF-beta and BMP-2 signal transduction, and played an important role in the bone formation. Cleidocranial dysplasia (CCD) was thought to be caused by heterozygous mutations in CBFA1. The CBFA1 knockout mice showed no osteogenesis and had maturational disturbance of chondrocytes. Smads and related transcription factors, especially Smad1, Smad5, Smad8 and CBFA1, play an important role in the signal transduction of BMPs inducing bone formation.

Bone marrow stimulation of the medial femoral condyle produces inferior cartilage and bone repair compared to the trochlea in a rabbit surgical model.

PubMed

Chen, Hongmei; Chevrier, Anik; Hoemann, Caroline D; Sun, Jun; Picard, Genevieve; Buschmann, Michael D

2013-11-01

The influence of the location of cartilage lesions on cartilage repair outcome is incompletely understood. This study compared cartilage and bone repair in medial femoral condylar (MFC) versus femoral trochlear (TR) defects 3 months after bone marrow stimulation in mature rabbits. Intact femurs from adult rabbits served as controls. Results from quantitative histomorphometry and histological scoring showed that bone marrow stimulation produced inferior soft tissue repair in MFC versus TR defects, as indicated by significantly lower % Fill (p = 0.03), a significant increase in collagen type I immunostaining (p < 0.00001) and lower O'Driscoll scores (p < 0.05). 3D micro-CT analysis showed that repaired TR defects regained normal un-operated values of bone volume fraction, trabecular thickness, and trabecular number, whereas in MFC defects the repaired bone architecture appeared immature and less dense compared to intact un-operated MFC controls (p < 0.0001). Severe medial meniscal damage was found in 28% of operated animals and was strongly correlated with (i) low cartilage defect fill, (ii) incomplete bone repair in MFC, and (iii) with a more posterior defect placement in the weight-bearing region. We conclude that the location of cartilage lesions influences cartilage repair, with better outcome in TR versus MFC defects in rabbits. Meniscal degeneration is associated with cartilage damage. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Low Bone Mineral Content and Challenges in Interpretation of Dual-Energy X-Ray Absorptiometry in Children With Mucopolysaccharidosis Types I, II, and VI

PubMed Central

Polgreen, Lynda E.; Thomas, William; Fung, Ellen; Viskochil, David; Stevenson, David A.; Steinberger, Julia; Orchard, Paul; Whitley, Chester B.; Ensrud, Kristine E.

2013-01-01

Osteoporosis has been described in animal models of mucopolysaccharidosis (MPS). Whether clinically significant osteoporosis is common among children with MPS is unknown. Therefore, cross-sectional data from whole body (WB; excluding head) and lumbar spine (LS) bone mineral density (BMD) compared with sex-, chronologic age–, and ethnicity-matched healthy individuals (Zage), height-for-age (HAZ) Z-score (ZHAZ) and bone mineral content (BMC) measured by dual-energy X-ray absorptiometry (DXA) in 40 children with MPS were analyzed. A subset of these children (n = 24) was matched 1:3 by age and sex to a group of healthy children (n = 72) for comparison of BMC adjusted for Tanner stage, race, lean body mass, height, and bone area. Low BMD Z-score was defined as Z-score of −2 or less. In children with MPS, 15% had low WB Zage and 48% had low LS Zage; 0% and 6% had low WB ZHAZ and low LS ZHAZ, respectively. Adjusted WB BMC was lower in MPS participants (p = 0.009). In conclusion, children with MPS had deficits in WB BMC after adjustments for stature and bone area. HAZ adjustment underestimated bone deficits (i.e., overestimated WB BMD Z-scores) in children with MPS likely owing to their abnormal bone shape. The influence of severe short stature and bone geometry on DXA measurements must be considered in children with MPS to avoid unnecessary exposure to antiresorptive treatments. PMID:23562131

Autologous Bone Marrow Concentrates and Concentrated Growth Factors Accelerate Bone Regeneration After Enucleation of Mandibular Pathologic Lesions.

PubMed

Talaat, Wael M; Ghoneim, Mohamed M; Salah, Omar; Adly, Osama A

2018-02-23

Stem cell therapy is a revolutionary new way to stimulate mesenchymal tissue regeneration. The platelets concentrate products started with platelet-rich plasma (PRP), followed by platelet-rich fibrin (PRF), whereas concentrated growth factors (CGF) are the latest generation of the platelets concentrate products which were found in 2011. The aim of the present study was to evaluate the potential of combining autologous bone marrow concentrates and CGF for treatment of bone defects resulting from enucleation of mandibular pathologic lesions. Twenty patients (13 males and 7 females) with mandibular benign unilateral lesions were included, and divided into 2 groups. Group I consisted of 10 patients who underwent enucleation of the lesions followed by grafting of the bony defects with autologous bone marrow concentrates and CGF. Group II consisted of 10 patients who underwent enucleation of the lesions without grafting (control). Radiographic examinations were done immediately postoperative, then at 1, 3, 6, and 12 months, to evaluate the reduction in size and changes in bone density at the bony defects. Results indicated a significant increase in bone density with respect to the baseline levels in both groups (P < 0.05). The increase in bone density was significantly higher in group I compared with group II at the 6- and 12-month follow-up examinations (P < 0.05). The percent of reduction in the defects' size was significantly higher in group I compared with group II after 12 months (P = 0.00001). In conclusion, the clinical application of autologous bone marrow concentrates with CGF is a cost effective and safe biotechnology, which accelerates bone regeneration and improves the density of regenerated bone.

Diabetes Alters Mechanical Properties and Collagen Fiber Re-Alignment in Multiple Mouse Tendons

PubMed Central

Connizzo, Brianne K.; Bhatt, Pankti R.; Liechty, Kenneth W.; Soslowsky, Louis J.

2014-01-01

Tendons function to transfer load from muscle to bone through their complex composition and hierarchical structure, consisting mainly of type I collagen. Recent evidence suggests that type II diabetes may cause alterations in collagen structure, such as irregular fibril morphology and density, which could play a role in the mechanical function of tendons. Using the db/db mouse model of type II diabetes, the diabetic skin was found to have impaired biomechanical properties when compared to the non-diabetic group. The purpose of this study was to assess the effect of diabetes on biomechanics, collagen fiber re-alignment, and biochemistry in three functionally different tendons (Achilles, supraspinatus, patellar) using the db/db mouse model. Results showed that cross-sectional area and stiffness, but not modulus, were significantly reduced in all three tendons. However, the tendon response to load (transition strain, collagen fiber re-alignment) occurred earlier in the mechanical test, contrary to expectations. In addition, the patellar tendon had an altered response to diabetes when compared to the other two tendons, with no changes in fiber realignment and decreased collagen content at the midsubstance of the tendon. Overall, type II diabetes alters tendon mechanical properties and the dynamic response to load. PMID:24833253

Modeling of Stiffness and Strength of Bone at Nanoscale.

PubMed

Abueidda, Diab W; Sabet, Fereshteh A; Jasiuk, Iwona M

2017-05-01

Two distinct geometrical models of bone at the nanoscale (collagen fibril and mineral platelets) are analyzed computationally. In the first model (model I), minerals are periodically distributed in a staggered manner in a collagen matrix while in the second model (model II), minerals form continuous layers outside the collagen fibril. Elastic modulus and strength of bone at the nanoscale, represented by these two models under longitudinal tensile loading, are studied using a finite element (FE) software abaqus. The analysis employs a traction-separation law (cohesive surface modeling) at various interfaces in the models to account for interfacial delaminations. Plane stress, plane strain, and axisymmetric versions of the two models are considered. Model II is found to have a higher stiffness than model I for all cases. For strength, the two models alternate the superiority of performance depending on the inputs and assumptions used. For model II, the axisymmetric case gives higher results than the plane stress and plane strain cases while an opposite trend is observed for model I. For axisymmetric case, model II shows greater strength and stiffness compared to model I. The collagen-mineral arrangement of bone at nanoscale forms a basic building block of bone. Thus, knowledge of its mechanical properties is of high scientific and clinical interests.

Masseter function and skeletal malocclusion.

PubMed

Sciote, J J; Raoul, G; Ferri, J; Close, J; Horton, M J; Rowlerson, A

2013-04-01

The aim of this work is to review the relationship between the function of the masseter muscle and the occurrence of malocclusions. An analysis was made of the masseter muscle samples from subjects who underwent mandibular osteotomies. The size and proportion of type-II fibers (fast) decreases as facial height increases. Patients with mandibular asymmetry have more type-II fibers on the side of their deviation. The insulin-like growth factor and myostatin are expressed differently depending on the sex and fiber diameter. These differences in the distribution of fiber types and gene expression of this growth factor may be involved in long-term postoperative stability and require additional investigations. Muscle strength and bone length are two genetically determined factors in facial growth. Myosin 1H (MYOH1) is associated with prognathia in Caucasians. As future objectives, we propose to characterize genetic variations using "Genome Wide Association Studies" data and their relationships with malocclusions. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Porous titanium and Ti-35Nb alloy: effects on gene expression of osteoblastic cells derived from human alveolar bone.

PubMed

do Prado, Renata Falchete; Rabêlo, Sylvia Bicalho; de Andrade, Dennia Perez; Nascimento, Rodrigo Dias; Henriques, Vinicius André Rodrigues; Carvalho, Yasmin Rodarte; Cairo, Carlos Alberto Alves; de Vasconcellos, Luana Marotta Reis

2015-11-01

Tests on titanium alloys that possess low elastic modulus, corrosion resistance and minimal potential toxicity are ongoing. This study aimed to evaluate the behavior of human osteoblastic cells cultured on dense and porous Titanium (Ti) samples comparing to dense and porous Ti-35 Niobium (Ti-35Nb) samples, using gene expression analysis. Scanning electronic microscopy confirmed surface porosity and pore interconnectivity and X-ray diffraction showed titanium beta-phase stabilization in Ti-35Nb alloy. There were no differences in expression of transforming growth factor-β, integrin-β1, alkaline phosphatase, osteopontin, macrophage colony stimulating factor, prostaglandin E synthase, and apolipoprotein E regarding the type of alloy, porosity and experimental period. The experimental period was a significant factor for the markers: bone sialoprotein II and interleukin 6, with expression increasing over time. Porosity diminished Runt-related transcription factor-2 (Runx-2) expression. Cells adhering to the Ti-35Nb alloy showed statistically similar expression to those adhering to commercially pure Ti grade II, for all the markers tested. In conclusion, the molecular mechanisms of interaction between human osteoblasts and the Ti-35Nb alloy follow the principal routes of osseointegration of commercially pure Ti grade II. Porosity impaired the route of transcription factor Runx-2.

Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.

PubMed

Zhang, Xiaowei; Wu, Shili; Naccarato, Ty; Prakash-Damani, Manan; Chou, Yuan; Chu, Cong-Qiu; Zhu, Yong

2017-01-01

Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP) (scSOX9) to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage.

A simple technique to strengthen the initial and mid-term to long-term stability of the cup during total hip arthroplasty in developmental dysplasia of the hip.

PubMed

Guan, Mingqiang; Zhou, Guanming; Li, Xue

2018-04-01

To assess the effects of a technique of cup blocking screws combined with impaction bone grafting during total hip arthroplasty (THA) for patients with developmental dysplasia of the hip (DDH). From August 2011 to July 2015, 53 patients (59 hips) with DDH in our hospital were treated with THA using the technique of cup blocking screws combined with impaction particulate bone grafting. These patients were prospectively followed, and the clinical and imaging results were collected. Harris hip score (HHS) was raised from 41.24 before surgery to 91.49 at the latest follow-up (p less than 0.001). Length discrepancy (LLD) was reduced from 28.97 mm before surgery to 6.08 mm after surgery (p less than 0.001). No loosening of the cup was detected at the last follow-up. The differences were insignificant in cup inclination and rate of cup coverage among the 3 groups of Crowe type II, type III, and type IV DDH (p greater than 0.05). The technique of cup blocking screws combined with impaction particulate bone grafting is simple and reliable, and it not only simplifies the attainment of initial stability, but also strengthens the mid-term to long-term stability during THA in DDH.

Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells

PubMed Central

Naccarato, Ty; Prakash-Damani, Manan; Chou, Yuan; Zhu, Yong

2017-01-01

Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP) (scSOX9) to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage. PMID:28666028

Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs.

PubMed

Murakami, S; Takayama, S; Kitamura, M; Shimabukuro, Y; Yanagi, K; Ikezawa, K; Saho, T; Nozaki, T; Okada, H

2003-02-01

Several growth factors (or cytokines) have been recently investigated for their use as potential therapeutics for periodontal tissue regeneration. The objective of this study was to evaluate periodontal tissue regeneration, including new bone and cementum formation, following topical application of recombinant basic fibroblast growth factor (bFGF, FGF-2) to furcation class II defects. Twelve furcation class II bone defects were surgically created in six beagle dogs, then recombinant bFGF (30 micro g/site) + gelatinous carrier was topically applied to the bony defects. Six weeks after application, periodontal regeneration was analyzed. In all sites where bFGF was applied, periodontal ligament formation with new cementum deposits and new bone formation was observed histomorphometrically, in amounts greater than in the control sites. Basic FGF-applied sites exhibited significant regeneration as represented by the new bone formation rate (NBR) (83.6 +/- 14.3%), new trabecular bone formation rate (NTBR) (44.1 +/- 9.5%), and new cementum formation rate (NCR) (97.0 +/- 7.5%). In contrast, in the carrier-only sites, the NBR, NTBR, and NCR were 35.4 +/- 8.9%, 16.6 +/- 6.2%, and 37.2 +/- 15.1%, respectively. Moreover, no instances of epithelial down growth, ankylosis, or root resorption were observed in the bFGF-applied sites examined. The present results indicate that topical application of bFGF can enhance considerable periodontal regeneration in artificially created furcation class II bone defects of beagle dogs.

Mathematical evaluation of the influence of multiple factors on implant stability quotient values in clinical practice: a retrospective study

PubMed Central

Huang, Hairong; Wismeijer, Daniel; Shao, Xianhong; Wu, Gang

2016-01-01

Objectives The objective of this study is to mathematically evaluate the influence of multiple factors on implant stability quotient values in clinical practice. Patients and methods Resonance frequency analysis was performed at T1 (measured immediately at the time of implant placement) and at T2 (measured before dental restoration) in 177 patients (329 implants). Using a multivariate linear regression model, we analyzed the influence of the following eleven candidate factors: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting (presence or absence), insertion torque, I-/II-stage healing pattern, implant diameter, implant length, and T1–T2 time interval. Results The following factors were identified to significantly influence the implant stability quotient (ISQ) values at T1: insertion torque, bone grafting, I-/II-stage healing pattern, immediate/delayed implantation, maxillary/mandibular location, implant diameter, and sex. In contrast, the ISQ values at T2 were significantly influenced only by three factors: implant diameter, T1–T2 time interval, and insertion torque. Conclusion Among the eleven candidate factors, seven key factors were found to influence the T1-ISQ values, while only three key factors influenced the T2-ISQ values. Both T1 and T2-ISQ values were found to be influenced by implant diameter and insertion torque. T1 was influenced specifically by the sex of the patient, the location (maxillary or mandibular), the implantation mode (immediate/delayed implantation), the healing stage, and the absence or presence of bone graft materials. PMID:27785040

Elastic fiber-mediated enthesis in the human middle ear.

PubMed

Kawase, Tetsuaki; Shibata, Shunichi; Katori, Yukio; Ohtsuka, Aiji; Murakami, Gen; Fujimiya, Mineko

2012-10-01

Adaptation to constant vibration (acoustic oscillation) is likely to confer a specific morphology at the bone-tendon and bone-ligament interfaces at the ear ossicles, which therefore represent an exciting target of enthesis research. We histologically examined (i) the bone attachments of the tensor tympani and stapedius muscles and (ii) the annular ligament of the incudostapedial joint obtained from seven elderly donated cadavers. Notably, both aldehyde-fuchsin and elastic-Masson staining demonstrated that the major fibrous component of the entheses was not collagen fibers but mature elastic fibers. The positive controls for elastic fiber staining were the arterial wall elastic laminae included in the temporal bone materials. The elastic fibers were inserted deeply into the type II collagen-poor fibrocartilage covering the ear ossicles. The muscle tendons were composed of an outer thin layer of collagen fibers and an inner thick core of elastic fibers near the malleus or stapes. In the unique elastic fiber-mediated entheses, hyaluronan, versican and fibronectin were expressed strongly along the elastic fibers. The hyaluronan seemed to act as a friction-reducing lubricant for the elastic fibers. Aggrecan was labeled strongly in a disk- or plica-like fibrous mass on the inner side of the elastic fiber-rich ligament, possibly due to compression stress from the ligament. Tenascin-c was not evident in the entheses. The elastic fiber-mediated entheses appeared resistant to tissue destruction in an environment exposed to constant vibration. The morphology was unlikely to be the result of age-related degeneration. © 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.

Effects of aluminum trichloride on the cartilage stimulatory growth factors in rats.

PubMed

Zhang, Fan; Sun, Xudong; Yu, Hongyan; Yang, Xu; Song, Miao; Han, Yanfei; Li, Yanfei; Zhu, Yanzhu

2017-02-01

Aluminum (Al) is considered to be a potentially toxic metal and inhibits cartilage formation. Transforming growth factor β1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) are cartilage stimulatory growth factors, which play important roles in regulating the cartilage formation. To investigate the effects of aluminum trichloride (AlCl 3 ) on the regulation of cartilage formation. Eighty Wistar rats were orally exposed to 0 (control group), 0.4 g/L (low-dose group), 0.8 g/L (mid-dose group) and 1.6 g/L (high-dose group) AlCl 3 for 120 days, respectively. The rats body weight were decreased, the cartilage histological structure were disrupted, the cartilage and serum contents of Al and the serum level of C-telopeptide of type II collagen were all increased, the serum level of type II collagen (Col II) and alkaline phosphatase (ALP), and the mRNA expressions of TGF-β1, BMP-2, ALP and Col II were all decreased in the AlCl 3 -treated groups compared with those in control group. These results indicate that AlCl 3 inhibits the cartilage formation through inhibition of the cartilage stimulatory growth factors expressions.

Addition of bone morphogenetic protein type 2 to ascorbate and β-glycerophosphate supplementation did not enhance osteogenic differentiation of human adipose-derived stem cells

PubMed Central

CRUZ, Ariadne Cristiane Cabral; SILVA, Mariana Lúcia; CAON, Thiago; SIMÕES, Cláudia Maria Oliveira

2012-01-01

Bone morphogenetic protein type 2 (BMP-2) is a potent local factor, which promotes bone formation and has been used as an osteogenic supplement for mesenchymal stem cells. Objectives This study evaluated the effect of a recombinant BMP-2 as well as the endogenous BMP-4 and BMP-7 in the osteogenic differentiation of adipose-derived stem cells (ASCs) in medium supplemented with ascorbate and β-glycerophosphate. Material and Methods Human ASCs were treated with osteogenic medium in the presence (ASCs+OM+BMP-2) or absence (ASCs+OM) of BMP-2. The alkaline phosphatase (ALP) activity was determined and the extracellular matrix mineralization was evaluated by Von Kossa staining and calcium quantification. The expressions of BMP-4, BMP-7, Smad1, Smad4, and phosphorylated Smad1/5/8 were analyzed by western blotting. Relative mRNA expressions of Smad1, BMP receptor type II (BMPR-II), osteonectin, and osteocalcin were evaluated by qPCR. Results: ASCs+OM demonstrated the highest expression of BMP-4 and BMP-7 at days 21 and 7, respectively, the highest levels of BMPR-II mRNA expression at day 28, and the highest levels of Smad1 mRNA at days 14 and 28. ASCs+OM+BMP-2 demonstrated the highest levels of Smad1 mRNA expression at days 1, 7, and 21, the highest expression of Smad1 at day 7, the highest expression of Smad4 at day 14, the highest ALP activity at days 14 and 21, and expression of phosphorylated Smad1/5/8 at day 7. ASCs+OM and ASCs+OM+BMP2 showed similar ALP activity at days 7 and 28, similar osteonectin and osteocalcin mRNA expression at all time periods, and similar calcium depositions at all time periods. Conclusions We concluded that human ASCs expressed endogenous BMP-4 and BMP-7. Moreover, the supplementation of ASCs with BMP-2 did not increase the level of osteogenic markers in the initial (ALP activity), intermediate (osteonectin and osteocalcin), or final (calcium deposition) phases, suggesting that the exogenous addition of BMP-2 did not improve the in vitro osteogenesis process of human ASCs. PMID:23329244

The challenge of Monteggia-like lesions of the elbow: mid-term results of 46 cases.

PubMed

Jungbluth, P; Tanner, S; Schneppendahl, J; Grassmann, J-P; Wild, M; Hakimi, M; Windolf, J; Laun, R

2018-02-01

The aim of this retrospective multicentre study was to evaluate mid-term results of the operative treatment of Monteggia-like lesions and to determine the prognostic factors that influence the clinical and radiological outcome. A total of 46 patients (27 women and 19 men), with a mean age of 57.7 years (18 to 84) who had sustained a Monteggia-like lesion were followed up clinically and radiologically after surgical treatment. The Mayo Modified Wrist Score (MMWS), Mayo Elbow Performance Score (MEPS), Broberg and Morrey Score, and Disabilities of the Arm, Shoulder and Hand (DASH) score were used for evaluation at a mean of 65 months (27 to 111) postoperatively. All ulnar fractures were stabilized using a proximally contoured or precontoured locking compression plate. Mason type I fractures of the radial head were treated conservatively, type II fractures were treated with reconstruction, and type III fractures with arthroplasty. All Morrey type II and III fractures of the coronoid process was stabilized using lag screws. Good results were found for the MMWS, with a mean of 88.4 (40 to 100). There were 29 excellent results (63%), nine good (20%), seven satisfactory (15%), and one poor (2%). Excellent results were obtained for the MEPS, with a mean of 90.7 (70 to 100): 31 excellent results (68%), 13 good (28%), and two fair (4%). Good results were also found for the functional rating index of Broberg and Morrey, with a mean score of 86.6 (57 to 100). There were 16 excellent results (35%), 22 good (48%), six fair (13%), and two poor (4%). The mean DASH score was 15.1 (0 to 55.8). Two patients had delayed wound healing; four patients had nonunion requiring bone grafting. One patient had asymptomatic loosening of the radial head prosthesis. Monteggia-like lesions are rare. With correct identification, classification, and understanding using CT scans followed by appropriate surgical treatment that addresses all components of the injury, good to excellent mid-term results can be achieved. Cite this article: Bone Joint J 2018;100-B:212-18. ©2018 The British Editorial Society of Bone & Joint Surgery.

Anabolic action of parathyroid hormone (PTH) does not compromise bone matrix mineral composition or maturation.

PubMed

Vrahnas, Christina; Pearson, Thomas A; Brunt, Athena R; Forwood, Mark R; Bambery, Keith R; Tobin, Mark J; Martin, T John; Sims, Natalie A

2016-12-01

Intermittent administration of parathyroid hormone (PTH) is used to stimulate bone formation in patients with osteoporosis. A reduction in the degree of matrix mineralisation has been reported during treatment, which may reflect either production of undermineralised matrix or a greater proportion of new matrix within the bone samples assessed. To explore these alternatives, high resolution synchrotron-based Fourier Transform Infrared Microspectroscopy (sFTIRM) coupled with calcein labelling was used in a region of non-remodelling cortical bone to determine bone composition during anabolic PTH treatment compared with region-matched samples from controls. 8week old male C57BL/6 mice were treated with vehicle or 50μg/kg PTH, 5 times/week for 4weeks (n=7-9/group). Histomorphometry confirmed greater trabecular and periosteal bone formation and 3-point bending tests confirmed greater femoral strength in PTH-treated mice. Dual calcein labels were used to match bone regions by time-since-mineralisation (bone age) and composition was measured by sFTIRM in six 15μm 2 regions at increasing depth perpendicular to the most immature bone on the medial periosteal edge; this allowed in situ measurement of progressive changes in bone matrix during its maturation. The sFTIRM method was validated in vehicle-treated bones where the expected progressive increases in mineral:matrix ratio and collagen crosslink type ratio were detected with increasing bone maturity. We also observed a gradual increase in carbonate content that strongly correlated with an increase in longitudinal stretch of the collagen triple helix (amide I:amide II ratio). PTH treatment did not alter the progressive changes in any of these parameters from the periosteal edge through to the more mature bone. These data provide new information about how the bone matrix matures in situ and confirm that bone deposited during PTH treatment undergoes normal collagen maturation and normal mineral accrual. Copyright © 2016 Elsevier Inc. All rights reserved.

Failure mechanisms and closed reduction of a constrained tripolar acetabular liner.

PubMed

Robertson, William J; Mattern, Christopher J; Hur, John; Su, Edwin P; Pellicci, Paul M

2009-02-01

Unlike traditional bipolar constrained liners, the Osteonics Omnifit constrained acetabular insert is a tripolar device, consisting of an inner bipolar bearing articulating within an outer, true liner. Every reported failure of the Omnifit tripolar implant has been by failure at the shell-bone interface (Type I failure), failure at the shell-liner interface (Type II failure), or failure of the locking mechanism resulting in dislocation of the bipolar-liner interface (Type III failure). In this report we present two cases of failure of the Omnifit tripolar at the bipolar-femoral head interface. To our knowledge, these are the first reported cases of failure at the bipolar-femoral head interface (Type IV failure). In addition, we described the first successful closed reduction of a Type IV failure.

Generation of the first Autosomal Dominant Osteopetrosis Type II (ADO2) disease models

PubMed Central

Alam, Imranul; Gray, Amie K.; Chu, Kang; Ichikawa, Shoji; Mohammad, Khalid S.; Capannolo, Marta; Capulli, Mattia; Maurizi, Antonio; Muraca, Maurizio; Teti, Anna; Econs, Michael J.; Fattore, Andrea Del

2013-01-01

Autosomal Dominant Osteopetrosis Type II (ADO2) is a heritable osteosclerotic disorder dependent on osteoclast impairment. In most patients it results from heterozygous missense mutations in the chloride channel 7 (CLCN7) gene, encoding for a 2Cl−/1H+ antiporter. By a knock-in strategy inserting a missense mutation in the Clcn7 gene, our two research groups independently generated mouse models of ADO2 on different genetic backgrounds carrying the homolog of the most frequent heterozygous mutation (p.G213R) in the Clcn7 gene found in humans. Our results demonstrate that the heterozygous model holds true presenting with higher bone mass, increased numbers of poorly resorbing osteoclasts and a lethal phenotype in the homozygous state. Considerable variability is observed in the heterozygous mice according with the mouse background, suggesting that modifier genes could influence the penetrance of the disease gene. PMID:24185277

Controlled Dual Growth Factor Delivery From Microparticles Incorporated Within Human Bone Marrow-Derived Mesenchymal Stem Cell Aggregates for Enhanced Bone Tissue Engineering via Endochondral Ossification.

PubMed

Dang, Phuong N; Dwivedi, Neha; Phillips, Lauren M; Yu, Xiaohua; Herberg, Samuel; Bowerman, Caitlin; Solorio, Loran D; Murphy, William L; Alsberg, Eben

2016-02-01

Bone tissue engineering via endochondral ossification has been explored by chondrogenically priming cells using soluble mediators for at least 3 weeks to produce a hypertrophic cartilage template. Although recapitulation of endochondral ossification has been achieved, long-term in vitro culture is required for priming cells through repeated supplementation of inductive factors in the media. To address this challenge, a microparticle-based growth factor delivery system was engineered to drive endochondral ossification within human bone marrow-derived mesenchymal stem cell (hMSC) aggregates. Sequential exogenous presentation of soluble transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) at various defined time courses resulted in varying degrees of chondrogenesis and osteogenesis as demonstrated by glycosaminoglycan and calcium content. The time course that best induced endochondral ossification was used to guide the development of the microparticle-based controlled delivery system for TGF-β1 and BMP-2. Gelatin microparticles capable of relatively rapid release of TGF-β1 and mineral-coated hydroxyapatite microparticles permitting more sustained release of BMP-2 were then incorporated within hMSC aggregates and cultured for 5 weeks following the predetermined time course for sequential presentation of bioactive signals. Compared with cell-only aggregates treated with exogenous growth factors, aggregates with incorporated TGF-β1- and BMP-2-loaded microparticles exhibited enhanced chondrogenesis and alkaline phosphatase activity at week 2 and a greater degree of mineralization by week 5. Staining for types I and II collagen, osteopontin, and osteocalcin revealed the presence of cartilage and bone. This microparticle-incorporated system has potential as a readily implantable therapy for healing bone defects without the need for long-term in vitro chondrogenic priming. Significance: This study demonstrates the regulation of chondrogenesis and osteogenesis with regard to endochondral bone formation in high-density stem cell systems through the controlled presentation of inductive factors from incorporated microparticles. This work lays the foundation for a rapidly implantable tissue engineering system that promotes bone repair via endochondral ossification, a pathway that can delay the need for a functional vascular network and has an intrinsic ability to promote angiogenesis. The modular nature of this system lends well to using different cell types and/or growth factors to induce endochondral bone formation, as well as the production of other tissue types. ©AlphaMed Press.

An evaluation of chondrocyte morphology and gene expression on superhydrophilic vertically-aligned multi-walled carbon nanotube films.

PubMed

Antonioli, Eliane; Lobo, Anderson O; Ferretti, Mario; Cohen, Moisés; Marciano, Fernanda R; Corat, Evaldo J; Trava-Airoldi, Vladimir J

2013-03-01

Cartilage serves as a low-friction and wear-resistant articulating surface in diarthrodial joints and is also important during early stages of bone remodeling. Recently, regenerative cartilage research has focused on combinations of cells paired with scaffolds. Superhydrophilic vertically aligned carbon nanotubes (VACNTs) are of particular interest in regenerative medicine. The aim of this study is to evaluate cell expansion of human articular chondrocytes on superhydrophilic VACNTs, as well as their morphology and gene expression. VACNT films were produced using a microwave plasma chamber on Ti substrates and submitted to an O2 plasma treatment to make them superhydrophilic. Human chondrocytes were cultivated on superhydrophilic VACNTs up to five days. Quantitative RT-PCR was performed to measure type I and type II Collagen, Sox9, and Aggrecan mRNA expression levels. The morphology was analyzed by scanning electron microscopy (SEM) and confocal microscopy. SEM images demonstrated that superhydrophilic VACNTs permit cell growth and adhesion of human chondrocytes. The chondrocytes had an elongated morphology with some prolongations. Chondrocytes cultivated on superhydrophilic VACNTs maintain the level expression of Aggrecan, Sox9, and Collagen II determined by qPCR. This study was the first to indicate that superhydrophilic VACNTs may be used as an efficient scaffold for cartilage or bone repair. Copyright © 2012 Elsevier B.V. All rights reserved.

Press-fit acetabular cup fixation: principles and testing.

PubMed

Macdonald, W; Carlsson, L V; Charnley, G J; Jacobsson, C M

1999-01-01

Pre-clinical testing of the fixation of press-fit acetabular components of total hip prostheses relies on cadaver or synthetic bone, but the properties and geometry of bone models differ from those of physiological bone. Cup designs use varied mechanisms for initial stability in bone; therefore, using different analogues and tests is appropriate. Press-fit cup stability was tested in the following: firstly, polyurethane (PU) foam modelling cancellous support; secondly, glass-fibre reinforced epoxide (GFRE) tubes modelling acetabular cortical support; thirdly, cadaveric acetabula. Three commercial cups [Harris-Galante II (H-G-II), Zimmer; Optifix, Smith & Nephew, Richards; porous coated anatomic (PCA), Howmedica] and an experimental cup with enhanced rim fixation were tested in three modes: direct pull-out, lever-out and axial torque. The fixation stabilities measured in the PU and the GFRE models showed trends consistent with those in cadaver bone, differing in the oversizing and cup geometry. The experimental cup was significantly more secure in most modes than other cups; the H-G II and Optifix cups showed similar stabilities, lower than that of the experimental cup but greater than that of the PCA cup (analysis of variance and Tukey's highly significant test; p < 0.001). The stabilities measured in cadaver bone more closely approximated those in GFRE. The use of several bone analogues enables separation of fixation mechanisms, allowing more accurate prediction of in vivo performance.

Myogenic progenitors contribute to open but not closed fracture repair.

PubMed

Liu, Renjing; Birke, Oliver; Morse, Alyson; Peacock, Lauren; Mikulec, Kathy; Little, David G; Schindeler, Aaron

2011-12-22

Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair. We employed a MyoD-Cre+:Z/AP+ conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a human alkaline phosphatase (hAP) reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing. In the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP+ cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP+ cells detected in the open fracture callus. At early stages of repair, many hAP+ cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP+ cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP+ staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors. These data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery. Please see related article: http://www.biomedcentral.com/1741-7015/9/136.

21 CFR 888.3150 - Elbow joint metal/polymer constrained cemented prosthesis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... use with bone cement (§ 888.3027). (b) Classification. Class II. The special controls for this device...) “Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone or Bone... Biomaterials (Nonporous) for Surgical Implant with Respect to Effect of Material on Muscle and Bone,” (v) F...

21 CFR 888.3150 - Elbow joint metal/polymer constrained cemented prosthesis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... use with bone cement (§ 888.3027). (b) Classification. Class II. The special controls for this device...) “Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone or Bone... Biomaterials (Nonporous) for Surgical Implant with Respect to Effect of Material on Muscle and Bone,” (v) F...

21 CFR 888.3150 - Elbow joint metal/polymer constrained cemented prosthesis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... use with bone cement (§ 888.3027). (b) Classification. Class II. The special controls for this device...) “Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone or Bone... Biomaterials (Nonporous) for Surgical Implant with Respect to Effect of Material on Muscle and Bone,” (v) F...

21 CFR 888.3150 - Elbow joint metal/polymer constrained cemented prosthesis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... use with bone cement (§ 888.3027). (b) Classification. Class II. The special controls for this device...) “Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone or Bone... Biomaterials (Nonporous) for Surgical Implant with Respect to Effect of Material on Muscle and Bone,” (v) F...

21 CFR 888.3150 - Elbow joint metal/polymer constrained cemented prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... use with bone cement (§ 888.3027). (b) Classification. Class II. The special controls for this device...) “Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone or Bone... Biomaterials (Nonporous) for Surgical Implant with Respect to Effect of Material on Muscle and Bone,” (v) F...

Bone alterations are associated with ankle osteoarthritis joint pain

PubMed Central

Nakamura, Yukio; Uchiyama, Shigeharu; Kamimura, Mikio; Komatsu, Masatoshi; Ikegami, Shota; Kato, Hiroyuki

2016-01-01

The etiology of ankle osteoarthritis (OA) is largely unknown. We analyzed 24 ankle OA of 21 patients diagnosed by plain radiographs using magnetic resonance imaging (MRI). Ankle joint pain disappeared in 22 out of 24 joints by conservative treatment. MRI bone signal changes in and around the ankle joints were observed in 22 of 24 joints. Bone signal changes along the joint line were seen in 10 of 11 joints as a Kellgren-Lawrence (KL) grade of II to IV. Such signal changes were witnessed in only 4 of 13 joints with KL grade 0 or I. In the talocrural joint, bone alterations occurred in both tibia and talus bones through the joint line in cases of KL grade III or IV, while focal bone alterations were present in the talus only in KL grade I or II cases. Sixteen of 24 joints exhibited intraosseous bone signal changes, which tended to correspond to joint pain of any ankle OA stage. Our results suggest that bone alterations around the ankle joint might be one of the etiologies of OA and associated with ankle joint pain. PMID:26776564

Bone alterations are associated with ankle osteoarthritis joint pain.

PubMed

Nakamura, Yukio; Uchiyama, Shigeharu; Kamimura, Mikio; Komatsu, Masatoshi; Ikegami, Shota; Kato, Hiroyuki

2016-01-18

The etiology of ankle osteoarthritis (OA) is largely unknown. We analyzed 24 ankle OA of 21 patients diagnosed by plain radiographs using magnetic resonance imaging (MRI). Ankle joint pain disappeared in 22 out of 24 joints by conservative treatment. MRI bone signal changes in and around the ankle joints were observed in 22 of 24 joints. Bone signal changes along the joint line were seen in 10 of 11 joints as a Kellgren-Lawrence (KL) grade of II to IV. Such signal changes were witnessed in only 4 of 13 joints with KL grade 0 or I. In the talocrural joint, bone alterations occurred in both tibia and talus bones through the joint line in cases of KL grade III or IV, while focal bone alterations were present in the talus only in KL grade I or II cases. Sixteen of 24 joints exhibited intraosseous bone signal changes, which tended to correspond to joint pain of any ankle OA stage. Our results suggest that bone alterations around the ankle joint might be one of the etiologies of OA and associated with ankle joint pain.

Evidence for an extensive collagen type III/VI proximal domain in the rat femur. I. Diminution with ovariectomy.

PubMed

Luther, F; Saino, H; Carter, D H; Aaron, J E

2003-06-01

Collagenous proteins other than Type I have received little attention in hypogonadal bone loss. Using femora from 25 young (2.5 months) and older (11 months) control and ovariectomized adult rats killed 1-4 months postoperation, cancellous atrophy was histologically confirmed, and the immunolocalization of collagen Type III was examined. This occurred as numerous immunofluorescent Sharpey-like fibers, 5-25 microm thick, regularly associated with collagen Type VI, which ramified the femoral cortex. Sequential transverse cryosections enabled the mapping of the fibers in three-dimensions, demonstrating that they constituted an extensive subperiosteal domain which may be a lasting legacy of early skeletal development. Fiber density was greatest in the trochanters and femoral neck. The domain tapered distally and was apparently anchored into the mid-shaft by intracortical cartilaginous islands, staining for collagen Type VI (as well as Type II and fibronectin). Ovariectomy caused disconnection of the fibers and reduced the proximal domain of both young and older animals, previously positive areas of the cortex becoming negative. It is concluded that collagen Type III/VI occupies a substantial, discrete domain in the rat proximal femur as a complex extension of the periosteum. Diminution of this cortical domain with trabecular atrophy suggests that it has a proactive or reactive role in determining bone mass and strength by facilitating musculoskeletal exchange in a form that is disengaged by ovariectomy.

Serum markers of bone turnover are increased by modest weight loss with or without weight-bearing exercise in overweight premenopausal women.

PubMed

Rector, R Scott; Loethen, Joanne; Ruebel, Meghan; Thomas, Tom R; Hinton, Pamela S

2009-10-01

Weight loss improves metabolic fitness and reduces morbidity and mortality; however, weight reduction also reduces bone mineral density (BMD) and increases bone turnover. Weight-bearing aerobic exercise may preserve bone mass and maintain normal bone turnover during weight reduction. We investigated the impact of weight-bearing and nonweight-bearing exercise on serum markers of bone formation and breakdown during short-term, modest weight loss in overweight premenopausal women. Subjects (n = 36) were assigned to 1 of 3 weight-loss interventions designed to produce a 5% reduction in body weight over 6 weeks: (i) energy restriction only (n = 11; DIET); (ii) energy restriction plus nonweight-bearing exercise (n = 12, CYCLE); or (iii) energy restriction plus weight-bearing exercise (n = 13, RUN). Bone turnover markers were measured in serum collected at baseline and after weight loss. All groups achieved a ~5% reduction in body weight (DIET = 5.2%; CYCLE = 5.0%; RUN = 4.7%). Osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX) increased with weight loss in all 3 groups (p < 0.05), whereas bone alkaline phosphatase was unaltered by the weight-loss interventions. At baseline, OC and CTX were positively correlated (r = 0.36, p = 0.03), but the strength of this association was diminished (r = 0.30, p = 0.06) after weight loss. Modest weight loss, regardless of method, resulted in a significant increase in both OC and CTX. Low-impact, weight-bearing exercise had no effect on serum markers of bone formation or resorption in premenopausal women during weight loss. Future studies that examine the effects of high-impact, weight-bearing activity on bone turnover and BMD during weight loss are warranted.

Metabolic Bone Disease in the Context of Metastatic Neuroendocrine Tumor: Differentiation from Skeletal Metastasis, the Molecular PET-CT Imaging Features, and Exploring the Possible Etiopathologies Including Parathyroid Adenoma (MEN1) and Paraneoplastic Humoral Hypercalcemia of Malignancy Due to PTHrP Hypersecretion.

PubMed

Ranade, Rohit; Basu, Sandip

2017-01-01

Three cases of metabolic bone disease in the setting of metastatic neuroendocrine tumor (NET) are illustrated with associated etiopathologies.  One of these cases harbored mixed lesions in the form of vertebral metastasis (biopsy proven) while the other skeletal lesions were caused due to metabolic bone disease related to multiple parathyroid adenomas. While the metastatic lesion was positive on 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT), the lesions of metabolic bone disease were negative and the 18F-fluoride PET-CT demonstrated the features of metabolic bone scan. Similar picture of metabolic bone disease [18-sodium fluoride (18NaF)/68Ga-DOTATATE mismatch] was documented in the other two patients, while fluorodeoxyglucose (FDG)-PET-CT was variably positive, primarily showing tracer uptake in the metabolic skeletal lesions of the patient with hypersecretion of parathyroid hormone-related protein (PTHrP) by the underlying tumor. Discordance between 18NaF PET-CT and 68Ga-DOTATATE PET-CT serves as a good marker for identification of metabolic bone disease and diagnosing such a clinical entity. In a patient of NET with metabolic bone disease and hypercalcemia, thus, two causes need to be considered: (i) Coexisting parathyroid adenoma in multiple endocrine neoplasia type I (MEN-I) syndrome and (ii) humoral hypercalcemia of malignancy (HHM) related to hypersecretion of PTHrP by the tumor. The correct diagnosis of metabolic bone disease in metastatic NET can alter the management substantially. Interestingly, peptide receptor radionuclide therapy (PRRT) can emerge as a very promising treatment modality in patients of metabolic bone disease caused by HHM in the setting of NET.

Effect of recombinant human bone morphogenetic protein-2 on bone regeneration and osseointegration of dental implants.

PubMed

Sykaras, N; Triplett, R G; Nunn, M E; Iacopino, A M; Opperman, L A

2001-08-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) induced bone regeneration and osseointegration was evaluated in bony defects created within the hollow chamber of endosseous dental implants in 14 foxhound dogs. Bilateral extractions of mandibular premolars were performed and surgical implantation of 104 hollow cylinder implants followed after 8 weeks of healing. Experimental implants had their hollow chamber filled with 20 microg of rhBMP-2 delivered with a bovine collagen carrier, whereas the control implants had their apical chamber left empty. Dogs were followed for 2, 4, 8 and 12 weeks. Histomorphometric evaluation and immunohistochemical analysis were performed. Minimal bone was regenerated at 2 weeks for both groups. At 4 weeks, bone fill averaged 23.48% for the rhBMP-2 and 5.98% for the control group (P<0.05). At 8 weeks, mean bone fill was 20.94% and 7.75% for the rhBMP-2 and the controls, respectively (P<0.05). At 12 weeks, mean bone fill was 31.39% and 24.31% for the rhBMP-2 and control implants, respectively (P>0.05). Bone-implant contact (BIC) increased for both groups over time and at 8 weeks the rhBMP-2 BIC value was 18.65% and for the control 7.22% (P<0.05). At 12 weeks, the BIC was 43.78% and 21.05% for the rhBMP-2 and the control group, respectively (P<0.05). Immunohistochemical staining for type II collagen was positive only for parts of the collagen carrier and formation of cartilaginous intermediate was not observed in any of the specimens. The results suggest that, in confined defects adjacent to dental implants, rhBMP-2 can induce bone regeneration in close apposition to the implant surface.

EFFECTS OF CHEMICAL PROCESSING AND OXIDE ETHYLENE STERILIZATION ON CORTICAL AND CANCELLOUS RAT BONE: A LIGHT AND ELECTRON SCANNING MICROSCOPY STUDY

PubMed Central

Castiglia, Marcello Teixeira; da Silva, Juliano Voltarelli F.; Frezarim Thomazini, José Armendir; Volpon, José Batista

2015-01-01

To evaluate, under microscopic examination, the structural changes displayed by the trabecular and cortical bones after being processed chemically and sterilized by ethylene oxide. Methods: Samples of cancellous and cortical bones obtained from young female albinus rats (Wistar) were assigned to four groups according to the type of treatment: Group I- drying; Group II- drying and ethylene oxide sterilization; III- chemical treatment; IV- chemical treatment and ethylene oxide sterilization. Half of this material was analyzed under ordinary light microscope and the other half using scanning electron microscopy. Results: In all the samples, regardless the group, there was good preservation of the general morphology. For samples submitted to the chemical processing there was better preservation of the cellular content, whereas there was amalgamation of the fibres when ethylene oxide was used. Conclusion: Treatment with ethylene oxide caused amalgamation of the fibers, possibly because of heating and the chemical treatment contributed to a better cellular preservation of the osseous structure. PMID:26998450

Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor

PubMed Central

1992-01-01

Antigen-presenting, major histocompatibility complex (MHC) class II- rich dendritic cells are known to arise from bone marrow. However, marrow lacks mature dendritic cells, and substantial numbers of proliferating less-mature cells have yet to be identified. The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II- negative precursors in marrow. A key step is to remove the majority of nonadherent, newly formed granulocytes by gentle washes during the first 2-4 d of culture. This leaves behind proliferating clusters that are loosely attached to a more firmly adherent "stroma." At days 4-6 the clusters can be dislodged, isolated by 1-g sedimentation, and upon reculture, large numbers of dendritic cells are released. The latter are readily identified on the basis of their distinct cell shape, ultrastructure, and repertoire of antigens, as detected with a panel of monoclonal antibodies. The dendritic cells express high levels of MHC class II products and act as powerful accessory cells for initiating the mixed leukocyte reaction. Neither the clusters nor mature dendritic cells are generated if macrophage colony-stimulating factor rather than granulocyte/macrophage colony-stimulating factor (GM-CSF) is applied. Therefore, GM-CSF generates all three lineages of myeloid cells (granulocytes, macrophages, and dendritic cells). Since > 5 x 10(6) dendritic cells develop in 1 wk from precursors within the large hind limb bones of a single animal, marrow progenitors can act as a major source of dendritic cells. This feature should prove useful for future molecular and clinical studies of this otherwise trace cell type. PMID:1460426

Preoperative Radiographic and CT Findings Predicting Syndesmotic Injuries in Supination-External Rotation-Type Ankle Fractures.

PubMed

Choi, Young; Kwon, Soon-Sun; Chung, Chin Youb; Park, Moon Seok; Lee, Seung Yeol; Lee, Kyoung Min

2014-07-16

The Lauge-Hansen classification system does not provide sufficient data related to syndesmotic injuries in supination-external rotation (SER)-type ankle fractures. The aim of the present study was to investigate factors helpful for the preoperative detection of syndesmotic injuries in SER-type ankle fractures using radiographs and computed tomography (CT). A cohort of 191 consecutive patients (104 male and eighty-seven female patients with a mean age [and standard deviation] of 50.7 ± 16.4 years) with SER-type ankle fractures who had undergone operative treatment were included. Preoperative ankle radiographs and CT imaging scans were made for all patients, and clinical data, including age, sex, and mechanism of injury (high or low-energy trauma), were collected. Patients were divided into two groups: the stable syndesmotic group and the unstable syndesmotic group, with a positive intraoperative lateral stress test leading to syndesmotic screw fixation. Fracture height, fracture length, medial joint space, extent of fracture, and bone attenuation were measured on radiographs and CT images and were compared between the groups. Binary logistic regression analysis was performed to identify the factors that significantly contributed to unstable syndesmotic injuries. Receiver operating characteristic curves were calculated, and cutoff values were suggested to predict unstable syndesmotic injuries on preoperative imaging measurements. Of the 191 patents with a SER-type ankle fracture, thirty-eight (19.9%) had a concurrent unstable syndesmotic injury. Age, sex, mechanism of injury, fracture height, medial joint space, and bone attenuation were significantly different between the two groups. In the binary logistic analysis, fracture height, medial joint space, and bone attenuation were found to be significant factors contributing to unstable syndesmotic injuries. The cutoff values for predicting unstable syndesmotic injuries were a fracture height of >3 mm and a medial joint space of >4.9 mm on CT scans, and a fracture height of >7 mm and medial joint space of >4.5 mm on radiographs. Fracture height, medial joint space, and bone attenuation were useful factors for the preoperative detection of unstable syndesmotic injuries in SER-type ankle fractures. Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Individual-specific multi-scale finite element simulation of cortical bone of human proximal femur

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ascenzi, Maria-Grazia, E-mail: mgascenzi@mednet.ucla.edu; Kawas, Neal P., E-mail: nealkawas@ucla.edu; Lutz, Andre, E-mail: andre.lutz@hotmail.de

2013-07-01

We present an innovative method to perform multi-scale finite element analyses of the cortical component of the femur using the individual’s (1) computed tomography scan; and (2) a bone specimen obtained in conjunction with orthopedic surgery. The method enables study of micro-structural characteristics regulating strains and stresses under physiological loading conditions. The analysis of the micro-structural scenarios that cause variation of strain and stress is the first step in understanding the elevated strains and stresses in bone tissue, which are indicative of higher likelihood of micro-crack formation in bone, implicated in consequent remodeling or macroscopic bone fracture. Evidence that micro-structuremore » varies with clinical history and contributes in significant, but poorly understood, ways to bone function, motivates the method’s development, as does need for software tools to investigate relationships between macroscopic loading and micro-structure. Three applications – varying region of interest, bone mineral density, and orientation of collagen type I, illustrate the method. We show, in comparison between physiological loading and simple compression of a patient’s femur, that strains computed at the multi-scale model’s micro-level: (i) differ; and (ii) depend on local collagen-apatite orientation and degree of calcification. Our findings confirm the strain concentration role of osteocyte lacunae, important for mechano-transduction. We hypothesize occurrence of micro-crack formation, leading either to remodeling or macroscopic fracture, when the computed strains exceed the elastic range observed in micro-structural testing.« less

A study of the progression of damage in an axially loaded Branta leucopsis femur using X-ray computed tomography and digital image correlation.

PubMed

Mustansar, Zartasha; McDonald, Samuel A; Sellers, William Irvin; Manning, Phillip Lars; Lowe, Tristan; Withers, Philip J; Margetts, Lee

2017-01-01

This paper uses X-ray computed tomography to track the mechanical response of a vertebrate (Barnacle goose) long bone subjected to an axial compressive load, which is increased gradually until failure. A loading rig was mounted in an X-ray computed tomography system so that a time-lapse sequence of three-dimensional (3D) images of the bone's internal (cancellous or trabecular) structure could be recorded during loading. Five distinct types of deformation mechanism were observed in the cancellous part of the bone. These were (i) cracking, (ii) thinning (iii) tearing of cell walls and struts, (iv) notch formation, (v) necking and (vi) buckling. The results highlight that bone experiences brittle (notch formation and cracking), ductile (thinning, tearing and necking) and elastic (buckling) modes of deformation. Progressive deformation, leading to cracking was studied in detail using digital image correlation. The resulting strain maps were consistent with mechanisms occurring at a finer-length scale. This paper is the first to capture time-lapse 3D images of a whole long bone subject to loading until failure. The results serve as a unique reference for researchers interested in how bone responds to loading. For those using computer modelling, the study not only provides qualitative information for verification and validation of their simulations but also highlights that constitutive models for bone need to take into account a number of different deformation mechanisms.

Insulin-Like Growth Factor Regulates Peak Bone Mineral Density in Mice by Both Growth Hormone-Dependent and -Independent Mechanisms

PubMed Central

Mohan, Subburaman; Richman, Charmaine; Guo, Rongqing; Amaar, Yousef; Donahue, Leah Rea; Wergedal, Jon; Baylink, David J.

2010-01-01

To evaluate the relative contribution of the GH/IGF axis to the development of peak bone mineral density (BMD), we measured skeletal changes in IGF-I knockout (KO), IGF-II KO, and GH-deficient lit/lit mice and their corresponding control mice at d 23 (prepubertal), 31 (pubertal), and 56 (postpubertal) in the entire femur by dual energy x-ray absorptiometry and in the mid-diaphysis by peripheral quantitative computed tomography. Lack of growth factors resulted in different degrees of failure of skeletal growth depending on the growth period and the growth factor involved. At d 23, femoral length, size, and BMD were reduced by 25–40%, 15–17%, and 8–10%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. During puberty, BMD increased by 40% in control mice and by 15% in IGF-II KO and GH-deficient mice, whereas it did not increase in the IGF-I KO mice. Disruption of IGF-I, but not IGF-II, completely prevented the periosteal expansion that occurs during puberty, whereas it was reduced by 50% in GH-deficient mice. At d 56, femoral length, size, and BMD were reduced by 40–55%, 11–18%, and 25–32%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. Our data demonstrate that: 1) mice deficient in IGF-I exhibit a greater impairment in bone accretion than mice deficient in IGF-II or GH; 2) GH/IGF-I, but not IGF-II, is critical for puberty-induced bone growth; and 3) IGF-I effects on bone accretion during prepuberty are mediated predominantly via mechanisms independent of GH, whereas during puberty they are mediated via both GH-dependent and GH-independent mechanisms. PMID:12586770

Production of hyaline-like cartilage by bone marrow mesenchymal stem cells in a self-assembly model.

PubMed

Elder, Steven H; Cooley, Avery J; Borazjani, Ali; Sowell, Brittany L; To, Harrison; Tran, Scott C

2009-10-01

A scaffoldless or self-assembly approach to cartilage tissue engineering has been used to produce hyaline cartilage from bone marrow-derived mesenchymal stem cells (bMSCs), but the mechanical properties of such engineered cartilage and the effects the transforming growth factor (TGF) isoform have not been fully explored. This study employs a cell culture insert model to produce tissue-engineered cartilage using bMSCs. Neonatal pig bMSCs were isolated by plastic adherence and expanded in monolayer before being seeded into porous transwell inserts and cultured for 4 or 8 weeks in defined chondrogenic media containing either TGF-beta1 or TGF-beta3. Following biomechanical evaluation in confined compression, colorimetric dimethyl methylene blue and Sircol dye-binding assays were used to analyze glycosaminoglycan (GAG) and collagen contents, respectively. Histological sections were stained with toluidine blue for proteoglycans and with picrosirius red to reveal collagen orientation, and immunostained for detection of collagen types I and II. Neocartilage increased in thickness, collagen, and GAG content between 4 and 8 weeks. Proteoglycan concentration increased with depth from the top surface. The tissue contained much more collagen type II than type I, and there was a consistent pattern of collagen alignment. TGF-beta1-treated and TGF-beta3-treated constructs were similar at 4 weeks, but 8-week TGF-beta1 constructs had a higher aggregate modulus and GAG content compared to TGF-beta3. These results demonstrate that bMSCs can generate functional hyaline-like cartilage through a self-assembling process.

An evaluation of bone scans as screening procedures for occult metastases in primary breast cancer.

PubMed Central

Baker, R R; Holmes, E R; Alderson, P O; Khouri, N F; Wagner, H N

1977-01-01

Preoperative bone scans were obtained in 104 patients with operable breast cancer. Areas of increased radioactivity detected by the bone scan were correlated with appropriate radiographs. One of 64 patients (1.5%) with clinical Stage I and Stage II breast cancer had a metastatic lesion detected by the preoperative bone scan. In contrast, 10 of 41 patients (24%) with Stage III breast cancer had occult metastatic lesions detected by the preoperative bone scan. The majority of patients with abnormal bone scans and no radiographic evidence of a benign lesion to explain the cause of the increased radioactivity proved to have metastatic breast cancer on follow-examination. Even though 20% of patients with operable breast cancer will eventually develop bone metastases, our results indicate that preoperative bone scans are not an effective means of predicting which patients with Stage I and Stage II disease will develop metastatic breast cancer. Because of the considerably increased frequency of detection of occult metastases in patients with Stage III breast cancer, bone scans should be obtained routinely in the preoperative assessment of these patients. Images Figs. 1a and b. Figs. 2a and b. Figs. 3a-d. PMID:889378

[Histopathological diagnostic work-up of joint endoprosthesis-associated pathologies].

PubMed

Krenn, V; Perino, G; Krenn, V T; Wienert, S; Saberi, D; Hügle, T; Hopf, F; Huber, M

2016-05-01

Increasing classes of joint implants and the combination of materials results in increased and wear-associated pathologies. According to the revised consensus classification, the following types can be recognized at conventional histological examination: Type I, particle-induced type; Type II, infection type; Type III, combination type; Type IV, indifferent type; Type V arthrofibrotic type; Type VI, allergic/immunological/toxic adverse reactions and Type VII, bone pathologies. Wear particles are histopathologically characterized according to the Krenn particle algorithm which focuses on a descriptive identification of wear particles and the differentiation of other nonwear-related particles. Type VII is considered histologically when there is evidence of a perivascular/interstitial lymphocytic CD20- and CD3-positive infiltrate, presence of mast cells and eosinophils, and tissue necrosis/infarction associated with implant wear material. Since wear particle-induced toxicity cannot be differentiated with certainty from hypersensitivity/allergic reaction on histological examination, immunological-allergological and clinical data should be used as supplementary criteria for the differential diagnosis. Tissue sampling should be performed from periprosthetic soft tissue with location mapping and when feasible also from bone tissue. Additional information regarding the type of implant and clinical, radiological, immunological, and microbiology data should be available to the pathologist. Further immunohistochemical studies are recommended in the following settings: infection (CD15, CD20, CD68); prosthesis-associated arthrofibrosis (β‑catenin); allergic/immunologic/toxic adverse reactions (CD20, CD3, CD4, CD8, CD117 and for T‑cell characterization T‑bet, GATA-3, and FOXP3).

Influence of stem design on the primary stability of megaprostheses of the proximal femur.

PubMed

Kinkel, Stefan; Graage, Jan Dennis; Kretzer, Jan Philippe; Jakubowitz, Eike; Nadorf, Jan

2013-10-01

Extended bone defects of the proximal femur can be reconstructed by megaprostheses for which aseptic loosening constitutes one of the major failure modes. The basic requirement for long-term success of endoprostheses is primary stability. We therefore assessed whether sufficient primary stability can be achieved by four different megaprostheses in a standardised bone defect of the proximal femur and whether their different design leads to different fixation patterns. Four different designs of proximal femoral replacements were implanted into 16 Sawbones® after preparing segmental bone defects (AAOS type II). Primary rotational stability was analysed by application of a cyclic torque of ±7 Nm and measuring the relative micromotions between bone and implant at different levels. The main fixation zones and differences of fixation patterns of the stem designs were determined by an analysis of variance. All four implants exhibited micromotions below 150 μm, indicating adequate primary stability. Lowest micromotions for all designs were located near the femoral isthmus. The extent of primary stability and the global implant fixation pattern differed considerably and could be related to the different design concepts. All megaprostheses studied provided sufficient primary stability if the fixation conditions of the femoral isthmus were intact. The design characteristics of the different stems largely determined the extent of primary stability and fixation pattern. Understanding these different fixation types could help the surgeon to choose the most suitable implant if the fixation conditions in the isthmus are compromised.

Development of a Multiplex Single Base Extension Assay for Mitochondrial DNA Haplogroup Typing

PubMed Central

Nelson, Tahnee M.; Just, Rebecca S.; Loreille, Odile; Schanfield, Moses S.; Podini, Daniele

2007-01-01

Aim To provide a screening tool to reduce time and sample consumption when attempting mtDNA haplogroup typing. Methods A single base primer extension assay was developed to enable typing, in a single reaction, of twelve mtDNA haplogroup specific polymorphisms. For validation purposes a total of 147 samples were tested including 73 samples successfully haplogroup typed using mtDNA control region (CR) sequence data, 21 samples inconclusively haplogroup typed by CR data, 20 samples previously haplogroup typed using restriction fragment length polymorphism (RFLP) analysis, and 31 samples of known ancestral origin without previous haplogroup typing. Additionally, two highly degraded human bones embalmed and buried in the early 1950s were analyzed using the single nucleotide polymorphisms (SNP) multiplex. Results When the SNP multiplex was used to type the 96 previously CR sequenced specimens, an increase in haplogroup or macrohaplogroup assignment relative to conventional CR sequence analysis was observed. The single base extension assay was also successfully used to assign a haplogroup to decades-old, embalmed skeletal remains dating to World War II. Conclusion The SNP multiplex was successfully used to obtain haplogroup status of highly degraded human bones, and demonstrated the ability to eliminate possible contributors. The SNP multiplex provides a low-cost, high throughput method for typing of mtDNA haplogroups A, B, C, D, E, F, G, H, L1/L2, L3, M, and N that could be useful for screening purposes for human identification efforts and anthropological studies. PMID:17696300

Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction.

PubMed

Fitch, J M; Gordon, M K; Gibney, E P; Linsenmayer, T F

1995-01-01

The genes for the alpha 1(IX), alpha 1(II), and alpha 2(I) collagen chains can give rise to different isoforms of mRNA, generated by alternative promotor usage [for alpha 1(IX) and alpha 2(I)] or alternative splicing [for alpha 1(II)]. In this study, we employed competitive reverse transcriptase PCR to quantitate the amounts of transcriptional isoforms for these genes in the embryonic avian cornea from its inception (about 3 1/2 days of development) to 11 days. In order to compare values at different time points, the results were normalized to those obtained for the "housekeeping" enzyme, glycerol-3-phosphate dehydrogenase (G3PDH). These values were compared to those obtained from other tissues (anterior optic cup and cartilage) that synthesize different combinations of the collagen isoforms. We found that, in the cornea, transcripts from the upstream promotor of alpha 1(IX) collagen (termed "long IX") were predominant at stage 18-20 (about 3 1/2 days), but then fell rapidly, and remained at a low level. By 5 days (just before stromal swelling) the major mRNA isoform of alpha 1(IX) was from the downstream promoter (termed "short IX"). The relative amount of transcript for the short form of type IX collagen rose to a peak at about 6 days of development, and then declined. Throughout this period, the predominant transcriptional isoform of the collagen type II gene was IIA (i.e., containing the alternatively spliced exon 2). This indicates that the molecules of type II collagen that are assembled into heterotypic fibrils with type I collagen possess, at least transiently, an amino-terminal globular domain similar to that found in collagen types I, III, and V. For type I, the "bone/tendon" mRNA isoform of the alpha 2(I) collagen gene was predominant; transcripts from the downstream promotor were at basal levels. In other tissues expressing collagen types IX and II, long IX was expressed predominantly with the IIA form in the anterior optic cup at stage 22/23; in 14 1/2 day cartilage, long IX was expressed predominantly along with the IIB form of alpha 1(II). The downstream transcript of the alpha 2(I) gene (Icart) was found at high levels only in cartilage.

Growth factors and cytokines in patients with long bone fractures and associated spinal cord injury.

PubMed

Khallaf, Fathy G; Kehinde, Elijah O; Mostafa, Ahmed

2016-06-01

The aim of the study was to test the effect of acute traumatic spinal cord injury of quadriplegia or paraplegia on bone healing in patients with associated long bone fractures and to investigate the molecular and cellular events of the underlying mechanism for a possible acceleration. Healing indicators of long bone fractures and growth factors, IGF-II, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), Activin-A, and cytokine I-L-1, in the patients' blood were calculated and measured for 21 patients with spinal cord injuries and associated long bone fractures in prospective controlled study and compared to 20 patients with only spinal cord injuries, 30 patients with only long bone fractures, and 30 healthy volunteers. The study results showed that long bone fractures in patients with associated acute traumatic spinal cord injury of quadriplegia or paraplegia heal more expectedly, faster, and with exuberant florid union callus (P > 0.001) and show statistically significant higher levels of growth factors like PDGF, VEGF, Activin-A, and cytokine I-L-1, along the 3 weeks of follow-up (P > 0.005). I-IGF-II showed statistically significant subnormal level along the whole follow-up period in the same patients (P > 0.005). We concluded that long bone fractures in spinal cord injury patients heal more expectedly, faster, and with exuberant and florid callus formation; growth factors like IGF-II, PDGF, VEGF, Activin-A, and cytokine I-L-I have roles as mediators, in molecular events and as byproducts of the subtle mechanism of accelerated osteogenesis in these patients and may represent therapeutic potentials to serve as agents to enhance bone repair.

Observations on the bony bridging of the jugular foramen in man.

PubMed

Dodo, Y

1986-02-01

The anatomical nature and pattern of incidence of bony bridging of the jugular foramen was investigated using 64 fetal crania aged nine months to term and 222 adult crania of Japanese. In addition, the region of the jugular foramen of an adult cadaver was carefully dissected in order to clarify the relationship between the cranial nerves passing through the jugular foramen and the intrajugular processes of the jugular foramen. The general conclusions concerning the anatomical nature of the bony bridging of the jugular foramen were as follows. (1) The intrajugular process of the temporal bone is situated posterior to the triangular depression (as described in Gray's Anatomy) of the petrous part. (2) The bony bridging of the jugular foramen is established by the contact of the intrajugular process of the temporal bone with the bony process of the occipital bone projecting either from just above the hypoglossal canal (Type I) or from posterior to the hypoglossal canal (Type III). (3) If both the processes of the occipital bone reach the intrajugular process of the temporal bone simultaneously, the jugular foramen is divided into three compartments. (4) In the case of Type I bridging, the anteromedial compartment transmits the glossopharyngeal nerve, while the posterolateral compartment gives passage to the vagus nerve, the accessory nerve and the internal jugular vein. (5) In the case of Type II bridging, the anteromedial compartment contains the glossopharyngeal, vagus and accessory nerves, and the posterolateral compartment transmits the internal jugular vein. (6) When tripartite division of the jugular foramen occurs, the anteromedial compartment transmits the glossopharyngeal nerve, the middle compartment contains the vagus and accessory nerves, and the posterolateral compartment transmits the internal jugular vein. Concerning the pattern of incidence of jugular foramen bridging in the Japanese fetal and adult cranial series, this is similar to that of the bony bridging of the hypoglossal canal. The fact that almost all the cases of bridging of the jugular foramen are already established by the end of fetal development must serve as a strong indication that this trait can be used effectively for anthropological population studies.

Prosthetic management of malpositioned implant using custom cast abutment

PubMed Central

Chatterjee, Aishwarya; Ragher, Mallikarjuna; Patil, Sanket; Chatterjee, Debopriya; Dandekeri, Savita; Prabhu, Vishnu

2015-01-01

Two cases are reported with malpositioned implants. Both the implants were placed 6–7 months back. They had osseointegrated well with the surrounding bone. However, they presented severe facial inclination. Case I was restored with custom cast abutment with an auto polymerizing acrylic gingival veneer. Case II was restored with custom cast UCLA type plastic implant abutment. Ceramic was directly fired on the custom cast abutments. The dual treatment strategy resulted in functional and esthetic restorations despite facial malposition of the implants. PMID:26538957

Molecular Imaging with Quantum Dots Probing EMT and Prostate Cancer Metastasis in Live Animals

DTIC Science & Technology

2006-10-01

Grignon DJ, Cher ML. Severe combined immunodeficient-humodel of humanprostate cancer metastasis to human bone. Cancer Res 1999;59(8): 1987 – 1993. 14... Eisler , H. J., and Bawendi, M. (2003) Type-II quantum dots: CdTe/CdSe(core/shell) and CdSe/ZinTe(core/shell) heterostructures. J. Am. Chem. Soc. 125...S1044. 39. Cunha GR, Donjacour AA, Cooke PS, et al. The endocrinology and developmen- tal biology of the prostate. Endocr Rev 1987 ; 8:338-362. 40

Cyclic hydrostatic pressure stimulates enhanced bone development in the foetal chick femur in vitro.

PubMed

Henstock, J R; Rotherham, M; Rose, J B; El Haj, A J

2013-04-01

Mechanical loading of bone and cartilage in vivo results in the generation of cyclic hydrostatic forces as bone compression is transduced to fluid pressure in the canalicular network and the joint synovium. It has therefore been suggested that hydrostatic pressure is an important stimulus by which osteochondral cells and their progenitors sense and respond to mechanical loading in vivo. In this study, hydrostatic pressure regimes of 0-279kPa at 0.005-2Hz were applied to organotypically cultured ex vivo chick foetal femurs (e11) for 1hour per day in a custom designed bioreactor for 14days and bone formation assessed by X-ray microtomography and qualified by histology. We found that the mineralised portion of the developing femur cultured under any cyclic hydrostatic pressure regime was significantly larger and/or denser than unstimulated controls but that constant (non-cycling) hydrostatic pressure had no effect on bone growth. Further experiments showed that the increase in bone formation was directly proportional to stimulation frequency (R(2)=0.917), but independent of the magnitude of the pressure applied, whilst even very low frequencies of stimulation (0.005Hz) had significant effects on bone growth. Expression of Type-II collagen in both epiphyses and diaphysis was significantly upregulated (1.48-fold and 1.95-fold respectively), together with osteogenic genes (osteonectin and osteopontin) and the osteocyte maturation marker CD44. This work demonstrates that cyclic hydrostatic pressure promotes bone growth and mineralisation in a developmental model and supports the hypothesis that hydrostatic forces play an important role in regulating bone growth and remodelling in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo.

PubMed

Frara, Nagat; Abdelmagid, Samir M; Sondag, Gregory R; Moussa, Fouad M; Yingling, Vanessa R; Owen, Thomas A; Popoff, Steven N; Barbe, Mary F; Safadi, Fayez F

2016-01-01

Initial identification of osteoactivin (OA)/glycoprotein non-melanoma clone B (gpnmb) was demonstrated in an osteopetrotic rat model, where OA expression was increased threefold in mutant bones, compared to normal. OA mRNA and protein expression increase during active bone regeneration post-fracture, and primary rat osteoblasts show increased OA expression during differentiation in vitro. To further examine OA/gpnmb as an osteoinductive agent, we characterized the skeletal phenotype of transgenic mouse overexpressing OA/gpnmb under the CMV-promoter (OA-Tg). Western blot analysis showed increased OA/gpnmb in OA-Tg osteoblasts, compared to wild-type (WT). In OA-Tg mouse femurs versus WT littermates, micro-CT analysis showed increased trabecular bone volume and thickness, and cortical bone thickness; histomorphometry showed increased osteoblast numbers, bone formation and mineral apposition rates in OA-Tg mice; and biomechanical testing showed higher peak moment and stiffness. Given that OA/gpnmb is also over-expressed in osteoclasts in OA-Tg mice, we evaluated bone resorption by ELISA and histomorphometry, and observed decreased serum CTX-1 and RANK-L, and decreased osteoclast numbers in OA-Tg, compared to WT mice, indicating decreased bone remodeling in OA-Tg mice. The proliferation rate of OA-Tg osteoblasts in vitro was higher, compared to WT, as was alkaline phosphatase staining and activity, the latter indicating enhanced differentiation of OA-Tg osteoprogenitors. Quantitative RT-PCR analysis showed increased TGF-β1 and TGF-β receptors I and II expression in OA-Tg osteoblasts, compared to WT. Together, these data suggest that OA overexpression has an osteoinductive effect on bone mass in vivo and stimulates osteoprogenitor differentiation ex vivo. © 2015 Wiley Periodicals, Inc.

Utility of bone scanning in detecting occult skeletal metastases from cervical carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katz, R.D.; Alderson, P.O.; Rosenshein, N.B.

1979-11-01

Bone scans were obtained in 100 patients with carcinoma of the cervix in order to search for occult skeletal metastases. Scans revealed metastases in 4 patients with advanced stages of disease, but the scans in 79 patients with Stage 0, I, or II disease were negative. The scans in 14 patients showed renal asymmetry; 11 of these had obstructive uropathy due to tumor invasion or radiation therapy. Bone scanning does not seem warranted as a screening test in asymptomatic patients with Stage 0, I, or II carcinoma. If the test is done, renal symmetry should be carefully evaluated.

[Symbrachydactyly].

PubMed

Samson, P; Mevio, G

2008-12-01

Symbrachydactyly is literally defined as a combination of short fingers with syndactyly. Blauth and Gekeler described four types of symbrachydactyly, ranging from simple shortness of middle phalanges to complete absence of digital rays. In type I (short finger) function is quite normal and syndactyly release is usually the only procedure needed. In type II (cleft hand), presence of a thumb and at least one ulnar finger allows pinch function. Surgical treatment, when needed, consists in separation of webbed fingers, resection of nonfunctional digital stumps, or finger translocation. In type III (monodactyly) all long fingers are absent. Pinch function can be created between the thumb and a toe transfer in ulnar location. Bone lengthening is an alternative procedure to create a pincer. Surgery is not always indicated in type IV (peromely) as function can only be restored if active motion is already present at wrist or carpometacarpal levels.

Reduced Appendicular Lean Body Mass, Muscle Strength, and Size of Type II Muscle Fibers in Patients with Spondyloarthritis versus Healthy Controls: A Cross-Sectional Study.

PubMed

Røren Nordén, Kristine; Dagfinrud, Hanne; Løvstad, Amund; Raastad, Truls

Introduction . The purpose of this study was to investigate body composition, muscle function, and muscle morphology in patients with spondyloarthritis (SpA). Methods . Ten male SpA patients (mean ± SD age 39 ± 4.1 years) were compared with ten healthy controls matched for sex, age, body mass index, and self-reported level of physical exercise. Body composition was measured by dual energy X-ray absorptiometry. Musculus quadriceps femoris (QF) strength was assessed by maximal isometric contractions prior to test of muscular endurance. Magnetic resonance imaging of QF was used to measure muscle size and calculate specific muscle strength. Percutaneous needle biopsy samples were taken from m. vastus lateralis . Results . SpA patients presented with significantly lower appendicular lean body mass (LBM) ( p = 0.02), but there was no difference in bone mineral density, fat mass, or total LBM. Absolute QF strength was significantly lower in SpA patients ( p = 0.03) with a parallel trend for specific strength ( p = 0.08). Biopsy samples from the SpA patients revealed significantly smaller cross-sectional area (CSA) of type II muscle fibers ( p = 0.04), but no difference in CSA type I fibers. Conclusions . Results indicate that the presence of SpA disease is associated with reduced appendicular LBM, muscle strength, and type II fiber CSA.

The clinical characteristics of patients with mitochondrial tRNA Leu(UUR)m.3243A > G mutation: Compared with type 1 diabetes and early onset type 2 diabetes.

PubMed

Zhu, Jie; Yang, Peng; Liu, Xiang; Yan, Li; Rampersad, Sharvan; Li, Feng; Li, Hong; Sheng, Chunjun; Cheng, Xiaoyun; Zhang, Manna; Qu, Shen

2017-08-01

This study presents nine patients with mitochondrial tRNA Leu (UUR) m.3243A>G mutation and compares the clinical characteristics and diabetes complications with type 1 diabetes (T1DM) or early onset type 2 diabetes (T2DM). The study covers 9 patients with MIDD, 33 patients with T1DM and 86 patients (age of onset ≤35years) with early onset T2DM, matched for sex, age at onset of diabetes, duration of diabetes. All patients with MIDD were confirmed as carrying the m.3243A>G mitochondrial DNA mutation. Serum HbA1c, beta-cell function, retinal and renal complications of diabetes, bone metabolic markers, lumbar spine and femoral neck BMD bone mineral density were compared to characterize the clinical features of all patients. Nine patients were from five unrelated families, and the mean (SD) onset age of those patients was 31.2±7.2year. Two patients required insulin at presentation, and six patients progressed to insulin requirement after a mean of 7.2years. β-Cell function in the MIDD group was intermediate between T1DM and early-onset T2DM. In MIDD, four patients were diagnosed as diabetic retinopathy (4/9) and five patients (5/9) had macroalbuminuria. The number of patients with diabetic retinopathy and macroalbuminuria in the MIDD group was comparable to T1DM or early-onset T2DM. The rate of osteoporosis (BMD T-score<-2.5 SD) in the patient with MIDD was higher than the T1DM or early-onset T2DM group. Our study indicates that of the nine subjects with MIDD, three patients (1-II-1, 1-II-3, 1-II-4) who came from the same family had a history of acute pancreatitis. Compared with T1DM or early-onset T2DM matched for sex, age, duration of diabetes, MIDD patients had the highest rate of osteoporosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Decreased miR-17-92 cluster expression level in serum and granulocytes preceding onset of antithyroid drug-induced agranulocytosis.

PubMed

Yang, Jing; Lv, Yuncheng; Zhang, Yi; Li, Jiaoyang; Chen, Yajun; Liu, Chang; Zhong, Jing; Xiao, Xinhua; Liu, Jianghua; Wen, Gebo

2018-01-01

We aimed to determine changes in miR-17-92 cluster expression in serum and granulocytes from patients with antithyroid drug (ATD)-induced agranulocytosis. In this study, real-time polymerase chain reaction (PCR) was used to detect serum miR-17-92 expression levels in 20 ATD-induced agranulocytosis and 16 control patients. Importantly, dynamic changes in neutrophil counts from granulocytopenia to agranulocytosis were observed in 6 of the 20 patients. miR-17-92 expression levels in granulocytes of those six patients under the granulocytopenia condition were measured and compared with corresponding granulocyte samples after recovery. Additionally, the expression levels of these miRNAs in patients with type I or type II bone marrow characteristics were analyzed, and the correlation between miR-17-92 and serum free thyroxine level was analyzed. We found that levels of miR-17-92 expression decreased in both serum and pre-agranulocytosis granulocytes from patients with ATD-induced agranulocytosis compared with those in serum and granulocytes from both recovered patients and control patients. However, no difference among patients with either type of bone marrow characteristics was observed, and no correlation between serum miR-17-92 and free thyroxine levels was found. In ATD-induced agranulocytosis, expression of the miR-17-92 cluster is reduced in both serum and granulocytes, though this alteration does not correlate with bone marrow characteristics or thyroid function.

The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).

PubMed

Joeris, Alexander; Lutz, Nicolas; Blumenthal, Andrea; Slongo, Theddy; Audigé, Laurent

2017-04-01

Background and purpose - To achieve a common understanding when dealing with long bone fractures in children, the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation, we present the most relevant fracture patterns in the upper extremities of a representative population of children classified according to the PCCF. Patients and methods - We included children and adolescents (0-17 years old) diagnosed with 1 or more long bone fractures between January 2009 and December 2011 at the university hospitals in Bern and Lausanne (Switzerland). Patient charts were retrospectively reviewed and fractures were classified from standard radiographs. Results - Of 2,292 upper extremity fractures in 2,203 children and adolescents, 26% involved the humerus and 74% involved the forearm. In the humerus, 61%, and in the forearm, 80% of single distal fractures involved the metaphysis. In adolescents, single humerus fractures were more often epiphyseal and diaphyseal fractures, and among adolescents radius fractures were more often epiphyseal fractures than in other age groups. 47% of combined forearm fractures were distal metaphyseal fractures. Only 0.7% of fractures could not be classified within 1 of the child-specific fracture patterns. Of the single epiphyseal fractures, 49% were Salter-Harris type-II (SH II) fractures; of these, 94% occurred in schoolchildren and adolescents. Of the metaphyseal fractures, 58% showed an incomplete fracture pattern. 89% of incomplete fractures affected the distal radius. Of the diaphyseal fractures, 32% were greenstick fractures. 24 Monteggia fractures occurred in pre-school children and schoolchildren, and 2 occurred in adolescents. Interpretation - The pattern of pediatric fractures in the upper extremity can be comprehensively described according to the PCCF. Prospective clinical studies are needed to determine its clinical relevance for treatment decisions and prognostication of outcome.

The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF)

PubMed Central

Joeris, Alexander; Lutz, Nicolas; Blumenthal, Andrea; Slongo, Theddy; Audigé, Laurent

2017-01-01

Background and purpose To achieve a common understanding when dealing with long bone fractures in children, the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation, we present the most relevant fracture patterns in the upper extremities of a representative population of children classified according to the PCCF. Patients and methods We included children and adolescents (0–17 years old) diagnosed with 1 or more long bone fractures between January 2009 and December 2011 at the university hospitals in Bern and Lausanne (Switzerland). Patient charts were retrospectively reviewed and fractures were classified from standard radiographs. Results Of 2,292 upper extremity fractures in 2,203 children and adolescents, 26% involved the humerus and 74% involved the forearm. In the humerus, 61%, and in the forearm, 80% of single distal fractures involved the metaphysis. In adolescents, single humerus fractures were more often epiphyseal and diaphyseal fractures, and among adolescents radius fractures were more often epiphyseal fractures than in other age groups. 47% of combined forearm fractures were distal metaphyseal fractures. Only 0.7% of fractures could not be classified within 1 of the child-specific fracture patterns. Of the single epiphyseal fractures, 49% were Salter-Harris type-II (SH II) fractures; of these, 94% occurred in schoolchildren and adolescents. Of the metaphyseal fractures, 58% showed an incomplete fracture pattern. 89% of incomplete fractures affected the distal radius. Of the diaphyseal fractures, 32% were greenstick fractures. 24 Monteggia fractures occurred in pre-school children and schoolchildren, and 2 occurred in adolescents. Interpretation The pattern of pediatric fractures in the upper extremity can be comprehensively described according to the PCCF. Prospective clinical studies are needed to determine its clinical relevance for treatment decisions and prognostication of outcome. PMID:27882802

Why is coronary collateral growth impaired in type II diabetes and the metabolic syndrome?

PubMed Central

Rocic, Petra

2012-01-01

Type II diabetes and the metabolic syndrome are strong predictors of severity of occlusive coronary disease and poorer outcomes of coronary revascularization therapies. Coronary collateral growth can provide an alternative or accessory pathway of revascularization. However, collateral growth is impaired in type II diabetes and the metabolic syndrome. Although many factors necessary for collateral growth are known and many interventions have shown promising results in animal studies, not a single attempt to induce coronary collateral growth in human clinical trials has led to satisfactory results. Accordingly, the first part of this review outlines the known deleterious effects of diabetes and the metabolic syndrome on factors necessary for collateral growth, including pro-angiogenic growth factors, endothelial function, the redox state of the coronary circulation, intracellular signaling, leukocytes and bone marrow-derived progenitors cells. The second section highlights the gaps in our current knowledge of how these factors interact with the radically altered environment of the coronary circulation in diabetes and the metabolic syndrome. The interplay between these pathologies and inadequately explored areas related to the temporal regulation of collateral remodeling and the roles of the extracellular matrix, vascular cell phenotype and pro-inflammatory cytokines are emphasized with implications to development of efficient therapies. PMID:22342811

Effect of angiotensin II receptor blocker, olmesartan, on turnover of bone metabolism in bedridden elderly hypertensive women with disuse syndrome.

PubMed

Aoki, Motokuni; Kawahata, Hirohisa; Sotobayashi, Daisuke; Yu, Hisahiro; Moriguchi, Atsushi; Nakagami, Hironori; Ogihara, Toshio; Morishita, Ryuichi

2015-08-01

Although recent studies suggest that several antihypertensive drugs could reduce the risk of bone fracture, it is still unclear how these drugs act on bone remodeling, especially in elderly women with severe osteoporosis with disuse syndrome. In the present study, we investigated the effects of a calcium channel blocker (CCB) and an angiotensin II receptor blocker (ARB) on bone metabolism in elderly bedridden women with hypertension and disuse syndrome. Elderly bedridden women (aged >75 years) receiving antihypertensive therapy treated with CCB were recruited in the present study. The participants were divided into two groups--CCB group and ARB group--and followed up to 12 months. Markers of bone resorption were markedly increased, suggesting accelerated bone resorption in the participants of the present study. In the follow-up period, the patients treated with a CCB showed a significant decrease in bone mineral density in a time-dependent manner, accompanied by a significant increase in bone resorption markers, whereas treatment with olmesartan inhibited bone loss, associated with attenuation of increased bone resorption markers. Bone mineral density of femoral neck in the CCB group was significantly lower than that in the ARB group at 6 months. The present study showed inhibitory effects of an ARB on bone resorption in hypertensive patients with accelerated bone resorption, such as elderly bedridden women, and indicated an important role of the renin-angiotensin system in bone metabolism. In elderly hypertensive patients, ARB might be expected to have additional beneficial potential to maintain bone health in bedridden patients. © 2014 Japan Geriatrics Society.

Roles of Osteonectin in Breast Cancer Metastasis to Bone

DTIC Science & Technology

2005-05-01

directed cell motility. Some 18 of these other factors within the mineralized matrix of bone could be bone sialoprotein and thrombospondin. Bone... sialoprotein has been shown to increase MDA-MB-231 cell migration in an RGD-dependent manner [14]. Another study has demonstrated the chemoattraction of MDA... sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone. J Biol Chem, 1987. 262(20): p. 9702-8. 7. Dayhoff, M.O

Positive modulator of bone morphogenic protein-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Positive modulator of bone morphogenic protein-2

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

2009-01-27

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

21 CFR 872.4600 - Intraoral ligature and wire lock.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Identification. An intraoral ligature and wire lock is a metal device intended to constrict fractured bone segments in the oral cavity. The bone segments are stabilized by wrapping the ligature (wire) around the fractured bone segments and locking the ends together. (b) Classification. Class II. ...

21 CFR 872.4600 - Intraoral ligature and wire lock.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Identification. An intraoral ligature and wire lock is a metal device intended to constrict fractured bone segments in the oral cavity. The bone segments are stabilized by wrapping the ligature (wire) around the fractured bone segments and locking the ends together. (b) Classification. Class II. ...

21 CFR 872.4600 - Intraoral ligature and wire lock.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Identification. An intraoral ligature and wire lock is a metal device intended to constrict fractured bone segments in the oral cavity. The bone segments are stabilized by wrapping the ligature (wire) around the fractured bone segments and locking the ends together. (b) Classification. Class II. ...

21 CFR 872.4600 - Intraoral ligature and wire lock.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Identification. An intraoral ligature and wire lock is a metal device intended to constrict fractured bone segments in the oral cavity. The bone segments are stabilized by wrapping the ligature (wire) around the fractured bone segments and locking the ends together. (b) Classification. Class II. ...

21 CFR 872.4600 - Intraoral ligature and wire lock.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Identification. An intraoral ligature and wire lock is a metal device intended to constrict fractured bone segments in the oral cavity. The bone segments are stabilized by wrapping the ligature (wire) around the fractured bone segments and locking the ends together. (b) Classification. Class II. ...

Melanocortin 1 receptor-signaling deficiency results in an articular cartilage phenotype and accelerates pathogenesis of surgically induced murine osteoarthritis.

PubMed

Lorenz, Julia; Seebach, Elisabeth; Hackmayer, Gerit; Greth, Carina; Bauer, Richard J; Kleinschmidt, Kerstin; Bettenworth, Dominik; Böhm, Markus; Grifka, Joachim; Grässel, Susanne

2014-01-01

Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT-analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA-pathology. Our data suggest that MC1-signaling protects against cartilage degradation and subchondral bone sclerosis in OA indicating a beneficial role of the POMC system in joint pathophysiology.

Melanocortin 1 Receptor-Signaling Deficiency Results in an Articular Cartilage Phenotype and Accelerates Pathogenesis of Surgically Induced Murine Osteoarthritis

PubMed Central

Hackmayer, Gerit; Greth, Carina; Bauer, Richard J.; Kleinschmidt, Kerstin; Bettenworth, Dominik; Böhm, Markus; Grifka, Joachim; Grässel, Susanne

2014-01-01

Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT–analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA-pathology. Our data suggest that MC1-signaling protects against cartilage degradation and subchondral bone sclerosis in OA indicating a beneficial role of the POMC system in joint pathophysiology. PMID:25191747

Mechanical induction of critically delayed bone healing in sheep: radiological and biomechanical results.

PubMed

Schell, Hanna; Thompson, Mark S; Bail, Hermann J; Hoffmann, Jan-Erik; Schill, Alexander; Duda, Georg N; Lienau, Jasmin

2008-10-20

This study aimed to mechanically produce a standardized ovine model for a critically delayed bone union. A tibial osteotomy was stabilized with either a rigid (group I) or mechanically critical (group II) external fixator in sheep. Interfragmentary movements and ground reaction forces were monitored throughout the healing period of 9 weeks. After sacrifice at 6 weeks, 9 weeks and 6 months, radiographs were taken and the tibiae were examined mechanically. Interfragmentary movements were considerably larger in group II throughout the healing period. Unlike group I, the operated limb in group II did not return to full weight bearing during the treatment period. Radiographic and mechanical observations showed significantly inferior bone healing in group II at 6 and 9 weeks compared to group I. After 6 months, five sheep treated with the critical fixator showed radiological bridging of the osteotomy, but the biomechanical strength of the repair was still inferior to group I at 9 weeks. The remaining three animals had even developed a hypertrophic non-union. In this study, mechanical instability was employed to induce a critically delayed healing model in sheep. In some cases, this approach even led to the development of a hypertrophic non-union. The mechanical induction of critical bone healing using an external fixation device is a reasonable attempt to investigate the patho-physiological healing cascade without suffering from any biological intervention. Therefore, the presented ovine model provides the basis for a comparative evaluation of mechanisms controlling delayed and standard bone healing.

Clinical Comparison of Autogenous Bone Graft with and without Plasma Rich in Growth Factors in the Treatment of Grade II Furcation Involvement of Mandibular Molars

PubMed Central

Lafzi, Ardeshir; Shirmohammadi, Adileh; Faramarzi, Masoumeh; Jabali, Sahar; Shayan, Arman

2013-01-01

Background and aims Plasma rich in growth factors (PRGF) is a concentrated suspension of growth factors, which is used to promote periodontal tissue regeneration. The aim of this randomized, controlled, clinical trial was to evaluate of the treatment of grade II mandibular molar furcation involvement using autogenous bone graft with and without PRGF. Materials and methods In this double-blind clinical trial, thirty mandibular molars with grade II furcation involvement in 30 patients were selected. The test group received bone graft combined with PRGF, while the control group was treated with bone graft only. Clinical parameters included clinical probing depth (CPD), vertical clinical attachment level (V-CAL), horizontal clinical attachment level (H-CAL), location of gingival margin (LGM), surgically exposed horizontal probing depth of bony defect (E-HPD), vertical depth of bone crest (V-DBC), vertical depth of the base of bony defect (V-DBD), and length of the intrabony defect (LID). After six months, a re-entry surgery was performed. Data were analyzed by SPSS 14, using Kolmogorov, Mann-Whitney U, and paired t-test. Results After 6 months, both treatment methods led to significant improvement in V-CAL and H-CAL and significant decreases in CPD, E-HPD, V-DBD and LID; there was no significant difference in LGM and V-DBC in any of the treated groups compared to the baseline values. Also, none of the parameters showed significant differences between the study groups. Conclusion Although autogenous bone grafts, with or without PRGF, were successful in treating grade II furcation involvement, no differences between the study groups were observed. PMID:23486928

Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation.

PubMed

Blouin, Stéphane; Fratzl-Zelman, Nadja; Glorieux, Francis H; Roschger, Paul; Klaushofer, Klaus; Marini, Joan C; Rauch, Frank

2017-09-01

In contrast to "classical" forms of osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain-of-function mutation in the IFITM5 gene, encoding the interferon-induced transmembrane protein 5, or bone-restricted interferon-inducible transmembrane (IFITM)-like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders such as hyperplastic callus and forearm interosseous membrane ossification. Little is known about the impact of the mutation on bone tissue/material level in untreated and bisphosphonate-treated patients. Therefore, investigations of transiliac bone biopsy samples from a cohort of OI type V children (n = 15, 8.7 ± 4 years old) untreated at baseline and a subset (n = 8) after pamidronate treatment (2.6 years in average) were performed. Quantitative backscattered electron imaging (qBEI) was used to determine bone mineralization density distribution (BMDD) as well as osteocyte lacunar density. The BMDD of type V OI bone was distinctly shifted toward a higher degree of mineralization. The most frequently occurring calcium concentration (CaPeak) in cortical (Ct) and cancellous (Cn) bone was markedly increased (+11.5%, +10.4%, respectively, p < 0.0001) compared to healthy reference values. Treatment with pamidronate resulted in only a slight enhancement of mineralization. The osteocyte lacunar density derived from sectioned bone area was elevated in OI type V Ct and Cn bone (+171%, p < 0.0001; +183.3%, p < 0.01; respectively) versus controls. The high osteocyte density was associated with an overall immature primary bone structure ("mesh-like") as visualized by polarized light microscopy. In summary, the bone material from OI type V patients is hypermineralized, similar to other forms of OI. The elevated osteocyte lacunar density in connection with lack of regular bone lamellation points to an exuberant primary bone formation and an alteration of the bone remodeling process in OI type V. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Characterizing the inorganic/organic interface in cancer bone metastasis

NASA Astrophysics Data System (ADS)

Wu, Fei

Bone metastasis frequently occurs in patients with advanced breast cancer and remains a major source of mortality. At the molecular level, bone is a nanocomposite composed of inorganic bone mineral deposited within an organic extracellular matrix (ECM). Although the exact mechanisms of bone metastasis remain unclear, the nanoscale materials properties of bone mineral have been implicated in this process. Bone apatite is closely related to synthetic hydroxyapatite (HAP, Ca10(PO4)6(OH)2) in terms of structural and mechanical properties. Additionally, although the primary protein content of bone is collagen I, the glycoprotein fibronectin (Fn) is essential in maintaining the overall integrity of the bone matrix. Importantly, in vivo, neither breast cancer cells nor normal bone cells interact directly with the bone mineral but rather with the protein film adsorbed onto the mineral surface. Therefore, we hypothesized that breast cancer cell functions were regulated by differential fibronectin adsorption onto hydroxyapatite, which led to pathological remodeling of the bone matrix and sustained bone metastasis. Three model systems containing HAP and Fn were developed for this thesis. In model system I, a library of synthetic HAP nanoparticles were utilized to investigate the effect of mineral size, shape, and crystallinity on Fn conformation, using Forster resonance energy transfer (FRET) spectroscopy. In model system II, Fn-functionalized large geologic HAP crystals were used instead of HAP nanoparticles to avoid cellular uptake when investigating subsequent cell functions. Overall our FRET analysis (models I and II) revealed that Fn conformation depended on size, surface chemistry, and roughness of underlying HAP. When breast cancer cells were seeded on the Fn-coated HAP crystal facets (model II), our data indicated high secretion levels of proangiogenic and proinflammatory factors associated with the presence of unfolded Fn conformations, likely caused by differential engagement of cell receptors integrins with the underlying Fn. Finally, in model system III, Fn fibrillar structures (mimicking the bone matrix) were fabricated and characterized in presence of HAP nanoparticles, suggesting that the presence of microcalcifications found in tumorous/inflammed tissues affects both the structural and mechanical properties of the surrounding ECM. Collectively, our study of cellular behavior regulated by mineral/ECM interactions provides insights into the pathogenesis of breast cancer bone metastasis as well as other HAP-related inflammation.

Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis.

PubMed

Bagger, Yu Z; Tankó, László B; Alexandersen, Peter; Karsdal, Morten A; Olson, Melvin; Mindeholm, Linda; Azria, Moïse; Christiansen, Claus

2005-09-01

To assess the efficacy of 3 months of oral salmon calcitonin (sCT) on cartilage degradation as estimated by the changes in the urinary excretion of C-terminal telopeptide of collagen type II (CTX-II), and to investigate whether the response of oral sCT to urinary CTX-II depends on the baseline level of cartilage turnover. This was a randomized, double blind, placebo-controlled clinical setting including 152 Danish postmenopausal women aged 55-85. The subjects received treatment with the different doses of sCT (0.15, 0.4, 1.0, or 2.5 mg) combined with Eligen technology-based carrier molecule (200 mg), or placebo for 3 months. The efficacy parameter was the changes in the 24-h excretion of urinary CTX-I/II corrected for creatinine excretion at month 3. sCT induced a significant dose-dependent decrease in 24-h urinary CTX-II excretion. Similar dose-dependent responses were found in 24-h urinary CTX-I. When stratifying the study population into tertiles of baseline urinary CTX-II, the present osteoarthritic symptoms and definite cases of osteoarthritis (OA) were significantly more frequent in women in the highest tertile of CTX-II (mean 391 +/- 18 ng/mmol). Women who received 1.0 mg of sCT and had the highest cartilage turnover presented the greatest decrease in urinary CTX-II after 3 months of treatment. In addition to its pronounced effect on bone resorption, this novel oral sCT formulation may also reduce cartilage degradation and thereby provide therapeutic benefit in terms of chondroprotection. Women with high cartilage turnover are more likely to benefit from oral sCT treatment.

Uremic toxin and bone metabolism.

PubMed

Iwasaki, Yoshiko; Yamato, Hideyuki; Nii-Kono, Tomoko; Fujieda, Ayako; Uchida, Motoyuki; Hosokawa, Atsuko; Motojima, Masaru; Fukagawa, Masafumi

2006-01-01

Patients with end-stage renal disease (ESRD) develop various kinds of abnormalities in bone and mineral metabolism, widely known as renal osteodystrophy (ROD). Although the pathogenesis of ESRD may be similar in many patients, the response of the bone varies widely, ranging from high to low turnover. ROD is classified into several types, depending on the status of bone turnover, by histomorphometric analysis using bone biopsy samples [1,2]. In the mild type, bone metabolism is closest to that of persons with normal renal function. In osteitis fibrosa, bone turnover is abnormally activated. This is a condition of high-turnover bone. A portion of the calcified bone loses its lamellar structure and appears as woven bone. In the cortical bone also, bone resorption by osteoclasts is active, and a general picture of bone marrow tissue infiltration and the formation of cancellous bone can be observed. In osteomalacia, the bone surface is covered with uncalcified osteoid. This condition is induced by aluminum accumulation or vitamin D deficiency. The mixed type possesses characteristics of both osteitis fibrosa and osteomalacia. The bone turnover is so markedly accelerated that calcification of the osteoid cannot keep pace. In the adynamic bone type, bone resorption and bone formation are both lowered. While bone turnover is decreased, there is little osteoid. The existence of these various types probably accounts for the diversity in degree of renal impairment, serum parathyroid hormone (PTH) level, and serum vitamin D level in patients with ROD. However, all patients share a common factor, i.e., the presence of a uremic condition.

Bone Cancer—Health Professional Version

Cancer.gov

There are several types of bone cancer. Osteosarcoma usually starts in osteoblasts, a type of bone cell that becomes new bone tissue. Ewing sarcoma arises from a primordial bone marrow–derived mesenchymal stem cell. Find evidence-based information on bone cancer including treatment, research, genetics, and statistics.

PvuII and XbaI polymorphisms of estrogen receptor-α and the results of estroprogestagen therapy in girls with functional hypothalamic amenorrhea – preliminary study

PubMed Central

Syrenicz, Anhelli; Friebe, Zbigniew; Jarząbek-Bielecka, Grażyna; Chełstowski, Kornel

2012-01-01

Introduction The aim of this study was the long-term prospective evaluation of the effects of estroprogestagen (EP) therapy on the bone mineral density (BMD) of girls with functional hypothalamic amenorrhea (FHA) carrying various PvuII and XbaI polymorphisms of ER-α. Material and methods Prospective observation included 84 FHA girls and 50 controls. The FHA patients were subjected to 4-year sequential therapy with 17β estradiol (2 mg from the 2nd to 25th day of the menstrual cycle) and dydrogesterone (10 mg from the 16th to the 25th day). Hormonal parameters, serum concentration of the bone fraction of alkaline phosphatase (BALP), urine concentration of cross-linked n-telopeptide of type I collagen (Ntx) and BMD were determined before and after the treatment. Results Six-month treatment resulted in a marked increase in estradiol (p = 0.001), testosterone and prolactin levels (p = 0.01 both) and a significant decrease in BALP and Ntx (p = 0.001 both). Patients with the PP polymorphism had significantly lower baseline BMD compared to carriers of other polymorphic variants of PvuII (p = 0.003). A significant increase in BMD was observed throughout the entire therapy period, with no significant differences in the yearly dynamics of BMD changes observed amongst various polymorphic variants and haplotypes of ER-α. Conclusions The EP therapy is effective in the treatment of BMD disorders associated with FHA, and treatment results do not depend on PvuII and XbaI polymorphisms of ER-α. PMID:23185193

PvuII and XbaI polymorphisms of estrogen receptor-α and the results of estroprogestagen therapy in girls with functional hypothalamic amenorrhea - preliminary study.

PubMed

Sowińska-Przepiera, Elżbieta; Syrenicz, Anhelli; Friebe, Zbigniew; Jarząbek-Bielecka, Grażyna; Chełstowski, Kornel

2012-11-09

The aim of this study was the long-term prospective evaluation of the effects of estroprogestagen (EP) therapy on the bone mineral density (BMD) of girls with functional hypothalamic amenorrhea (FHA) carrying various PvuII and XbaI polymorphisms of ER-α. Prospective observation included 84 FHA girls and 50 controls. The FHA patients were subjected to 4-year sequential therapy with 17β estradiol (2 mg from the 2(nd) to 25(th) day of the menstrual cycle) and dydrogesterone (10 mg from the 16(th) to the 25(th) day). Hormonal parameters, serum concentration of the bone fraction of alkaline phosphatase (BALP), urine concentration of cross-linked n-telopeptide of type I collagen (Ntx) and BMD were determined before and after the treatment. Six-month treatment resulted in a marked increase in estradiol (p = 0.001), testosterone and prolactin levels (p = 0.01 both) and a significant decrease in BALP and Ntx (p = 0.001 both). Patients with the PP polymorphism had significantly lower baseline BMD compared to carriers of other polymorphic variants of PvuII (p = 0.003). A significant increase in BMD was observed throughout the entire therapy period, with no significant differences in the yearly dynamics of BMD changes observed amongst various polymorphic variants and haplotypes of ER-α. The EP therapy is effective in the treatment of BMD disorders associated with FHA, and treatment results do not depend on PvuII and XbaI polymorphisms of ER-α.

Autologous periodontal ligament cells in the treatment of class II furcation defects: a study in dogs.

PubMed

Suaid, Fabricia Ferreira; Ribeiro, Fernanda Vieira; Rodrigues, Thaisângela L; Silvério, Karina Gonzales; Carvalho, Marcelo Diniz; Nociti, Francisco Humberto; Casati, Marcio Zaffalon; Sallum, Enilson Antônio

2011-05-01

The goal of this study was to histologically investigate the use of periodontal ligament cells (PDL cells) in tissue engineering to regenerate class II furcation defects. PDL cells were obtained from the mandibular tooth extracted from each dog (seven), cultured in vitro and phenotypically characterized with regard to their biological properties. Following, bilateral class II furcation lesions were created at maxillary 3rd premolars and were randomly assigned to the test group [PDL cells+guided tissue regeneration (GTR)] or the control group (GTR). After 3 months, the animals were euthanized to evaluate the histometric parameters. In vitro, PDL cells were able to promote mineral nodule formation and to express bone sialoprotein, type I collagen and alkaline phosphatase. Histometrically, data analysis demonstrated that the cell-treated group presented a superior length of new cementum (6.00 ± 1.50 and 8.08 ± 1.08 mm), a greater extension of periodontal regeneration (3.94 ± 1.20 and 7.28 ± 1.00 mm), a lower formation of connective tissue/epithelium (2.15 ± 1.92 and 0.60 ± 0.99 mm), a larger area of new bone (7.01 ± 0.61 and 9.02 ± 2.30 mm(2)) and a smaller area of connective tissue/epithelium (5.90 ± 1.67 and 4.22 ± 0.95 mm(2)), when compared with control group. PDL cells in association with GTR may significantly promote periodontal regeneration in class II furcation defects in dog. © 2011 John Wiley & Sons A/S.

Ultrastructure Organization of Human Trabeculae Assessed by 3D sSAXS and Relation to Bone Microarchitecture

PubMed Central

Guizar-Sicairos, Manuel; Gschwend, Oliver; Hangartner, Peter; Bunk, Oliver; Müller, Ralph; Schneider, Philipp

2016-01-01

Although the organization of bone ultrastructure, i.e. the orientation and arrangement of the mineralized collagen fibrils, has been in the focus of research for many years for cortical bone, and many models on the osteonal arrangement have been proposed, limited attention has been paid to trabecular bone ultrastructure. This is surprising because trabeculae play a crucial role for the mechanical strength of several bone sites, including the vertebrae and the femoral head. On this account, we first validated a recently developed method (3D sSAXS or 3D scanning small-angle X-ray scattering) for investigating bone ultrastructure in a quantitative and spatially resolved way, using conventional linearly polarized light microscopy as a gold standard. While both methods are used to analyze thin tissue sections, in contrast to polarized light microscopy, 3D sSAXS has the important advantage that it provides 3D information on the orientation and arrangement of bone ultrastructure. In this first study of its kind, we used 3D sSAXS to investigate the ultrastructural organization of 22 vertebral trabeculae of different alignment, types and sizes, obtained from 4 subjects of different ages. Maps of ultrastructure orientation and arrangement of the trabeculae were retrieved by stacking information from consecutive 20-μm-thick bone sections. The organization of the ultrastructure was analyzed in relation to trabecular microarchitecture obtained from computed tomography and to relevant parameters such as distance to trabecular surface, local curvature or local bone mineralization. We found that (i) ultrastructure organization is similar for all investigated trabeculae independent of their particular characteristics, (ii) bone ultrastructure exhibiting a high degree of orientation was arranged in domains, (iii) highly oriented ultrastructural areas were located closer to the bone surface, (iv) the ultrastructure of the human trabecular bone specimens followed the microarchitecture, being oriented mostly parallel to bone surface, and (v) local surface curvature seems to have an effect on the ultrastructure organization. Further studies that investigate bone ultrastructure orientation and arrangement are needed in order to understand its organization and consequently its relation to bone biology and mechanics. PMID:27547973

A study of the progression of damage in an axially loaded Branta leucopsis femur using X-ray computed tomography and digital image correlation

PubMed Central

Manning, Phillip Lars; Lowe, Tristan; Withers, Philip J.

2017-01-01

This paper uses X-ray computed tomography to track the mechanical response of a vertebrate (Barnacle goose) long bone subjected to an axial compressive load, which is increased gradually until failure. A loading rig was mounted in an X-ray computed tomography system so that a time-lapse sequence of three-dimensional (3D) images of the bone’s internal (cancellous or trabecular) structure could be recorded during loading. Five distinct types of deformation mechanism were observed in the cancellous part of the bone. These were (i) cracking, (ii) thinning (iii) tearing of cell walls and struts, (iv) notch formation, (v) necking and (vi) buckling. The results highlight that bone experiences brittle (notch formation and cracking), ductile (thinning, tearing and necking) and elastic (buckling) modes of deformation. Progressive deformation, leading to cracking was studied in detail using digital image correlation. The resulting strain maps were consistent with mechanisms occurring at a finer-length scale. This paper is the first to capture time-lapse 3D images of a whole long bone subject to loading until failure. The results serve as a unique reference for researchers interested in how bone responds to loading. For those using computer modelling, the study not only provides qualitative information for verification and validation of their simulations but also highlights that constitutive models for bone need to take into account a number of different deformation mechanisms. PMID:28652932

Clinical application of bone morphogenetic proteins for bone healing: a systematic review.

PubMed

Krishnakumar, Gopal Shankar; Roffi, Alice; Reale, Davide; Kon, Elizaveta; Filardo, Giuseppe

2017-06-01

This paper documents the existing evidence on bone morphogenetic proteins (BMPs) use for the treatment of bone fractures, non-union, and osteonecrosis, through a review of the clinical literature, underlying potential and limitations in terms of cost effectiveness and risk of complications. A systematic review was performed on the PubMed database using the following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone regeneration) including papers from 2000 to 2016. The search focused on clinical trials dealing with BMPs application to favor bone regeneration in bone fractures, non-union, and osteonecrosis, in English language, with level of evidence I, II, III, and IV. Relevant data (type of study, number of patients, BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were extracted and analyzed. Forty-four articles met the inclusion criteria: 10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series, and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures, and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found among RCTs and comparative papers: 11 reported positive results for BMPs augmentation, 3 obtained no significant effects, and 2 showed negative results. The only study comparing the two BMPs showed a better outcome with rhBMP-2 for non-union treatment. Clinical evidence on BMPs use for the treatment of fractures, non-union, and osteonecrosis is still controversial, with the few available reports being mainly of low quality. While positive findings have been described in many studies, mixed results are still present in the literature in terms of efficacy and adverse events. The difficulties in drawing clear conclusions are also due to the studies heterogeneity, mainly in terms of different BMPs applied, with different concomitant treatments for each bone pathology. Therefore, further research with well-designed studies is needed in order to understand the real potential of this biological approach to favour bone healing.

Human mesenchymal stem cells and biomaterials interaction: a promising synergy to improve spine fusion.

PubMed

Barbanti Brodano, G; Mazzoni, E; Tognon, M; Griffoni, C; Manfrini, M

2012-05-01

Spine fusion is the gold standard treatment in degenerative and traumatic spine diseases. The bone regenerative medicine needs (i) in vitro functionally active osteoblasts, and/or (ii) the in vivo induction of the tissue. The bone tissue engineering seems to be a very promising approach for the effectiveness of orthopedic surgical procedures, clinical applications are often hampered by the limited availability of bone allograft or substitutes. New biomaterials have been recently developed for the orthopedic applications. The main characteristics of these scaffolds are the ability to induce the bone tissue formation by generating an appropriate environment for (i) the cell growth and (ii) recruiting precursor bone cells for the proliferation and differentiation. A new prototype of biomaterials known as "bioceramics" may own these features. Bioceramics are bone substitutes mainly composed of calcium and phosphate complex salt derivatives. In this study, the characteristics bioceramics bone substitutes have been tested with human mesenchymal stem cells obtained from the bone marrow of adult orthopedic patients. These cellular models can be employed to characterize in vitro the behavior of different biomaterials, which are used as bone void fillers or three-dimensional scaffolds. Human mesenchymal stem cells in combination with biomaterials seem to be good alternative to the autologous or allogenic bone fusion in spine surgery. The cellular model used in our study is a useful tool for investigating cytocompatibility and biological features of HA-derived scaffolds.

Reconstruction of maxillectomy and midfacial defects with free tissue transfer.

PubMed

Santamaria, Eric; Cordeiro, Peter G

2006-11-01

The maxillary bones are part of the midfacial skeleton and are closely related to the eyeglobe, nasal airway, and oral cavity. Together with the overlying soft tissues, the two maxillae are responsible to a large extent for facial contour. Maxillectomy defects become more complex when critical structures such as the orbit, globe, and cranial base are resected, and reconstruction with distant tissues become essential. In this article, we describe a classification system and algorithm for reconstruction of these complex defects using various pedicled and free flaps. Most defects that involve resection of the maxilla and adjacent soft tissues may be classified into one of the following four types: Type I defects, Limited maxillectomy; Type II defects, Subtotal maxillectomy; Type III defects, Total maxillectomy; and Type IV defects, Orbitomaxillectomy. Using this classification, reconstruction of maxillectomy and midfacial defects may be approached considering the relationship between volume and surface area requirements, that is, addressing the bony defect first, followed by assessment of the associated soft tissue, skin, palate, and cheek-lining deficits. In our experience, most complex maxillectomy defects are best reconstructed using free tissue transfer. The rectus abdominis and radial forearm free flap in combination with immediate bone grafting or as an osteocutaneous flap reliably provide the best aesthetic and functional results. A temporalis muscle pedicled flap is used for reconstruction of maxillectomy defects only in those patients who are not candidates for a microsurgical procedure.

Denosumab treatment of prostate cancer with bone metastases and increased urine N-telopeptide levels after therapy with intravenous bisphosphonates: results of a randomized phase II trial.

PubMed

Fizazi, Karim; Bosserman, Linda; Gao, Guozhi; Skacel, Tomas; Markus, Richard

2009-08-01

Patients with bone metastases have high rates of RANKL driven bone resorption and an increased risk of skeletal morbidity. Osteoclast mediated bone resorption can be assessed by measuring urine N-telopeptide and can be inhibited by denosumab, a fully human antibody against RANKL. Eligible patients (111) had bone metastases from prostate cancer, other solid tumors or multiple myeloma, 1 or more bone lesions and urine N-telopeptide greater than 50 nM bone collagen equivalents per mM creatinine (urine N-telopeptide greater than 50) despite the use of intravenous bisphosphonates. Patients were stratified by cancer type and screening urine N-telopeptide, and randomized to continue intravenous bisphosphonates every 4 weeks or receive 180 mg subcutaneous denosumab every 4 weeks or 180 mg every 12 weeks. The primary end point was the proportion of patients with urine N-telopeptide less than 50 at week 13. We report the efficacy results for the subset of patients with prostate cancer. Patients with prostate cancer represented 45% (50 of 111) of the study population. At week 13, 22 of 32 (69%) patients in the denosumab arms had urine N-telopeptide less than 50 vs 3 of 16 (19%) in the intravenous bisphosphonates cohort. At week 25, 22 of 32 (69%) denosumab treated patients continued to have urine N-telopeptide less than 50 vs 5 of 16 (31%) treated with intravenous bisphosphonates. Grade 4, asymptomatic, reversible hypophosphatemia, possibly related to denosumab, was reported in 1 patient. In patients with prostate cancer related bone metastases and increased urine N-telopeptide despite intravenous bisphosphonate treatment, denosumab normalized urine N-telopeptide levels more frequently than ongoing intravenous bisphosphonates.

21 CFR 882.5900 - Preformed craniosynostosis strip.

Code of Federal Regulations, 2010 CFR

2010-04-01

... bone edges of craniectomy sites (sites where the skull has been cut) to prevent the bone from regrowing in patients whose skull sutures are abnormally fused together. (b) Classification. Class II...

[Effect of the middle ear status on the recording of vestibular evoked myogenic potential--VEMP].

PubMed

Kurzyna, Agnieszka; Hassmann-Poznańska, Elzbieta; Topolska, Małgorzata Maria

2004-01-01

The aim of this study was to assess the effect of age on the recording of air- and bone-conducted vestibular evoked myogenic potential. Forty six young subjects were included in the study, ranging in age from 4 to 18 years. All of them underwent otoscopy, pure tone audiometry, tympanometry and air- and bone-conducted VEMP in response to click. Eighty six ears with normal hearing (pure tone average 20 dB) and type A and C1 tympanogram were studied. There were 2 groups according to age: group I--children aged 4-10 years--52 ears, group II--young subjects aged 11-18 years--34 ears. The threshold, the presence of correct waveform morphology of the response and the latency were evaluated. Above parameters were examined at 95 dB and 100 dB (nHL) air conducted click intensity and 60 dB (nHL) bone conducted click intensity. The age has no significant effect on the percentage of the recording of VEMP and the level of the response threshold with air stimulation, based on the performed studies. However, the age has effect on the prolongation of latency p13 and n23 both with air and bone stimulation. We paid attention to the lower percentage of the recording of bone-conducted VEMP in young subjects aged 11-18 years.

Fabrication of Metallic Biomedical Scaffolds with the Space Holder Method: A Review

PubMed Central

Arifvianto, Budi; Zhou, Jie

2014-01-01

Bone tissue engineering has been increasingly studied as an alternative approach to bone defect reconstruction. In this approach, new bone cells are stimulated to grow and heal the defect with the aid of a scaffold that serves as a medium for bone cell formation and growth. Scaffolds made of metallic materials have preferably been chosen for bone tissue engineering applications where load-bearing capacities are required, considering the superior mechanical properties possessed by this type of materials to those of polymeric and ceramic materials. The space holder method has been recognized as one of the viable methods for the fabrication of metallic biomedical scaffolds. In this method, temporary powder particles, namely space holder, are devised as a pore former for scaffolds. In general, the whole scaffold fabrication process with the space holder method can be divided into four main steps: (i) mixing of metal matrix powder and space-holding particles; (ii) compaction of granular materials; (iii) removal of space-holding particles; (iv) sintering of porous scaffold preform. In this review, detailed procedures in each of these steps are presented. Technical challenges encountered during scaffold fabrication with this specific method are addressed. In conclusion, strategies are yet to be developed to address problematic issues raised, such as powder segregation, pore inhomogeneity, distortion of pore sizes and shape, uncontrolled shrinkage and contamination. PMID:28788638

Rotating three-dimensional dynamic culture of adult human bone marrow-derived cells for tissue engineering of hyaline cartilage.

PubMed

Sakai, Shinsuke; Mishima, Hajime; Ishii, Tomoo; Akaogi, Hiroshi; Yoshioka, Tomokazu; Ohyabu, Yoshimi; Chang, Fei; Ochiai, Naoyuki; Uemura, Toshimasa

2009-04-01

The method of constructing cartilage tissue from bone marrow-derived cells in vitro is considered a valuable technique for hyaline cartilage regenerative medicine. Using a rotating wall vessel (RWV) bioreactor developed in a NASA space experiment, we attempted to efficiently construct hyaline cartilage tissue from human bone marrow-derived cells without using a scaffold. Bone marrow aspirates were obtained from the iliac crest of nine patients during orthopedic operation. After their proliferation in monolayer culture, the adherent cells were cultured in the RWV bioreactor with chondrogenic medium for 2 weeks. Cells from the same source were cultured in pellet culture as controls. Histological and immunohistological evaluations (collagen type I and II) and quantification of glycosaminoglycan were performed on formed tissues and compared. The engineered constructs obtained using the RWV bioreactor showed strong features of hyaline cartilage in terms of their morphology as determined by histological and immunohistological evaluations. The glycosaminoglycan contents per microg DNA of the tissues were 10.01 +/- 3.49 microg/microg DNA in the case of the RWV bioreactor and 6.27 +/- 3.41 microg/microg DNA in the case of the pellet culture, and their difference was significant. The RWV bioreactor could provide an excellent environment for three-dimensional cartilage tissue architecture that can promote the chondrogenic differentiation of adult human bone marrow-derived cells.

Engineering of hyaline cartilage with a calcified zone using bone marrow stromal cells.

PubMed

Lee, W D; Hurtig, M B; Pilliar, R M; Stanford, W L; Kandel, R A

2015-08-01

In healthy joints, a zone of calcified cartilage (ZCC) provides the mechanical integration between articular cartilage and subchondral bone. Recapitulation of this architectural feature should serve to resist the constant shear force from the movement of the joint and prevent the delamination of tissue-engineered cartilage. Previous approaches to create the ZCC at the cartilage-substrate interface have relied on strategic use of exogenous scaffolds and adhesives, which are susceptible to failure by degradation and wear. In contrast, we report a successful scaffold-free engineering of ZCC to integrate tissue-engineered cartilage and a porous biodegradable bone substitute, using sheep bone marrow stromal cells (BMSCs) as the cell source for both cartilaginous zones. BMSCs were predifferentiated to chondrocytes, harvested and then grown on a porous calcium polyphosphate substrate in the presence of triiodothyronine (T3). T3 was withdrawn, and additional predifferentiated chondrocytes were placed on top of the construct and grown for 21 days. This protocol yielded two distinct zones: hyaline cartilage that accumulated proteoglycans and collagen type II, and calcified cartilage adjacent to the substrate that additionally accumulated mineral and collagen type X. Constructs with the calcified interface had comparable compressive strength to native sheep osteochondral tissue and higher interfacial shear strength compared to control without a calcified zone. This protocol improves on the existing scaffold-free approaches to cartilage tissue engineering by incorporating a calcified zone. Since this protocol employs no xenogeneic material, it will be appropriate for use in preclinical large-animal studies. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

[Proposal for the classification of the periprosthetic membrane from loosened hip and knee endoprostheses].

PubMed

Morawietz, L; Gehrke, Th; Classen, R-A; Barden, B; Otto, M; Hansen, T; Aigner, Th; Stiehl, P; Neidel, J; Schröder, J H; Frommelt, L; Schubert, Th; Meyer-Scholten, C; König, A; Ströbel, Ph; Rader, Ch P; Kirschner, S; Lintner, F; Rüther, W; Skwara, A; Bos, I; Kriegsmann, J; Krenn, V

2004-09-01

After 10 years, loosening of total joint endoprostheses occurs in about 3 to 10 percent of all patients, requiring elaborate revision surgery. A periprosthetic membrane is routinely found between bone and loosened prosthesis. Further histomorphological examination allows determination of the etiology of the loosening process. Aim of this study is the introduction of clearly defined histopathological criteria for a standardized evaluation of the periprosthetic membrane. Based on histomorphological criteria and polarized light microscopy, four types of the periprosthetic membrane were defined: periprosthetic membrane of wear particle type (type I), periprosthetic membrane of infectious type (type II), periprosthetic membrane of combined type (type III), periprosthetic membrane of indifferent type (type IV). Periprosthetic membranes of 268 patients were analyzed according to the defined criteria. The correlation between histopathological and microbiological diagnosis was high (89%, p<0,001), the inter-observer reproducibility was sufficient (95%). This classification system enables a standardized diagnostic procedure and therefore is a basis for further studies concerning the etiology of and pathogenesis of prosthesis loosening.

Defective postnatal endochondral bone development by chondrocyte-specific targeted expression of parathyroid hormone type 2 receptor.

PubMed

Panda, Dibyendu Kumar; Goltzman, David; Karaplis, Andrew C

2012-12-15

The human parathyroid hormone type 2 receptor (PTH2R) is activated by PTH and by tuberoinfundibular peptide of 39 residues (TIP39), the latter likely acting as its natural ligand. Although the receptor is expressed at highest levels in the nervous system, we have observed that both PTH2R and TIP39 are expressed in the newborn mouse growth plate, with the receptor localizing in the resting zone and the ligand TIP39 localizing exclusively in prehypertrophic and hypertrophic chondrocytes. To address the role of PTH2R in postnatal skeletal growth and development, Col2a1-hPTH2R (PTH2R-Tg) transgenic mice were generated. The mice were viable and of nearly normal size at birth. Expression of the transgene in the growth plate was limited to chondrocytes. We found that chondrocyte proliferation was decreased, as determined by in vivo BrdU labeling of proliferating chondrocytes and CDK4 and p21 expression in the growth plate of Col2a1-hPTH2R transgenic mice. Similarly, the differentiation and maturation of chondrocytes was delayed, as characterized by decreased Sox9 expression and weaker immunostaining for the chondrocyte differentiation markers collagen type II and type X and proteoglycans. As well, there was altered expression of Gdf5, Wdr5, and β-catenin, factors implicated in chondrocyte maturation, proliferation, and differentiation.These effects impacted on the process of endochondral ossification, resulting in delayed formation of the secondary ossification center, and diminished trabecular bone volume. The findings substantiate a role for PTH2R signaling in postnatal growth plate development and subsequent bone mass acquisition.

Role of Adrenomedullin in Breast Cancer Bone Metastasis and Chemoresistance

DTIC Science & Technology

2008-05-01

osteoblast proliferation but does not induce bone matrix protein (bone sialoprotein , type I collagen, osteocalcin, and osteopontin) mRNA expression...are incompletely understood. AM treatment stimulates osteoblast proliferation but does not induce bone matrix protein (bone sialoprotein , type I

Soft tissue recurrence of giant cell tumor of the bone: Prevalence and radiographic features.

PubMed

Xu, Leilei; Jin, Jing; Hu, Annan; Xiong, Jin; Wang, Dongmei; Sun, Qi; Wang, Shoufeng

2017-11-01

Recurrence of giant cell tumor of bone (GCTB) in the soft tissue is rarely seen in the clinical practice. This study aims to determine the prevalence of soft tissue recurrence of GCTB, and to characterize its radiographic features. A total of 291 patients treated by intralesional curettage for histologically diagnosed GCTB were reviewed. 6 patients were identified to have the recurrence of GCTB in the soft tissue, all of whom had undergone marginal resection of the lesion. Based on the x-ray, CT and MRI imaging, the radiographic features of soft tissue recurrence were classified into 3 types. Type I was defined as soft tissue recurrence with peripheral ossification, type II was defined as soft tissue recurrence with central ossification, and type III was defined as pure soft tissue recurrence without ossification. Demographic data including period of recurrence and follow-up duration after the second surgery were recorded for these 6 patients. Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate functional outcomes. The overall recurrence rate was 2.1% (6/291). The mean interval between initial surgery and recurrence was 11.3 ± 4.1 months (range, 5-17). The recurrence lesions were located in the thigh of 2 patients, in the forearm of 2 patients and in the leg of the other 2 patients. According to the classification system mentioned above, 2 patients were classified with type I, 1 as type II and 3 as type III. After the marginal excision surgery, all patients were consistently followed up for a mean period of 13.4 ± 5.3 months (range, 6-19), with no recurrence observed at the final visit. All the patients were satisfied with the surgical outcome. According to the MSTS scale, the mean postoperative functional score was 28.0 ± 1.2 (range, 26-29). The classification of soft tissue recurrence of GCTB may be helpful for the surgeon to select the appropriate imaging procedure to detect the recurrence. In addition, the marginal resection can produce a favorable outcome for the patients.

[Pedicled vascularized bone grafts from the dorsum of the distal radius for treatment of scaphoid nonunions].

PubMed

Sauerbier, Michael; Bishop, Allen T; Ofer, Nina

2009-11-01

Bony healing and reconstruction of the scaphoid with use of a reverse-flow pedicle vascularized bone graft from the dorsal aspect of the distal radius. Revitalization of the proximal fragment in case of avascular necrosis. Scaphoid nonunion, especially of the proximal pole. Nonunion after failed attempts of autogenous nonvascularized bone grafting. Avascular necrosis of the scaphoid (Preiser's disease). Avascular osteonecrosis of other carpal bones (i.e., Kienböck's disease stage II and IIIa). However, these will not be addressed in this paper. Advance carpal collapse (SNAC [scaphoid nonunion advanced collapse] wrist stage II and III). Avascular necrosis with broken proximal pole of the scaphoid. Malformation, disease or previous injury of the vascular system. Reconstruction of the scaphoid by interposition of a vascularized bone graft from the dorsum of the distal radius, where several vascularized bone grafts can be harvested, and fixation by a scaphoid screw. Management Immobilization for 6 weeks in a forearm cast including the first phalanx of the thumb. 48 scaphoid nonunions were treated with 1,2-ICSRA-based (intercompartmental supraretinacular artery) vascularized bone grafts: 34 scaphoid nonunions went on to union at an average of 15.6 weeks after surgery.

75 FR 43533 - Medicare Program; Meeting of the Medicare Evidence Development and Coverage Advisory Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

... and off-label use of bone morphogenetic proteins (BMPs). This meeting is open to the public in... use of bone morphogenetic proteins. Background information about this topic, including panel materials... appropriate organizations with expertise in the use of bone morphogenetic protein. II. Meeting Format This...

The Influence of Primary Microenvironment on Prostate Cancer Osteoblastic Bone Lesion Development

DTIC Science & Technology

2015-09-01

for inhibiting PCa bone lesion development: 3a. Basic fibroblast growth factor (bFGF) in PC3 bone metastasis: bFGF was identified by cytokine...II receptor (TβRII) knockout (Tgfbr2 KO) mouse models. Col1creERT/Tgfbr2 KO (Col/Tgfbr2 KO), which have TGF-β signaling specific KO in fibroblasts ... fibroblasts and osteoblasts in the bone by Colcre/Tgfbr2 KO, or in the myeloid lineage cells, including osteoclasts in the bone by LysMcre/Tgfbr2 KO

Osteoinductive effects of glyceollins on adult mesenchymal stromal/stem cells from adipose tissue and bone marrow.

PubMed

Bateman, Marjorie E; Strong, Amy L; Hunter, Ryan S; Bratton, Melyssa R; Komati, Rajesh; Sridhar, Jayalakshmi; Riley, Kevin E; Wang, Guangdi; Hayes, Daniel J; Boue, Stephen M; Burow, Matthew E; Bunnell, Bruce A

2017-04-15

While current therapies for osteoporosis focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabolic therapy candidates include phytoestrogens, such as daidzein, which effectively induce osteogenesis of adipose-derived stromal cells (ASCs) and bone marrow stromal cells (BMSCs). To investigate the effects of glyceollins, structural derivatives of daidzein, on osteogenesis of ASCs and BMSCs. Herein, the osteoinductive effects of glyceollin I and glyceollin II were assessed and compared to estradiol in ASCs and BMSCs. The mechanism by which glyceollin II induces osteogenesis was further examined. The ability of glyceollins to promote osteogenesis of ASCs and BMSCs was evaluated in adherent and scaffold cultures. Relative deposition of calcium was analyzed using Alizarin Red staining, Bichinchoninic acid Protein Assay, and Alamar Blue Assay. To further explore the mechanism by which glyceollin II exerts its osteoinductive effects, docking studies of glyceollin II, RNA isolation, cDNA synthesis, and quantitative RT-PCR (qPCR) were performed. In adherent cultures, ASCs and BMSCs treated with estradiol, glyceollin I, or glyceollin II demonstrated increased calcium deposition relative to vehicle-treated cells. During evaluation on PLGA scaffolds seeded with ASCs and BMSCs, glyceollin II was the most efficacious in inducing ASC and BMSC osteogenesis compared to estradiol and glyceollin I. Dose-response analysis in ASCs and BMSCs revealed that glyceollin II has the highest potency at 10nM in adherent cultures and 1µM in tissue scaffold cultures. At all doses, osteoinductive effects were attenuated by fulvestrant, suggesting that glyceollin II acts at least in part through estrogen receptor-mediated pathways to induce osteogenesis. Analysis of gene expression demonstrated that, similar to estradiol, glyceollin II induces upregulation of genes involved in osteogenic differentiation. The ability of glyceollin II to induce osteogenic differentiation in ASCs and BMSCs indicates that glyceollins hold the potential for the development of pharmacological interventions to improve clinical outcomes of patients with osteoporosis. Copyright © 2017 Elsevier GmbH. All rights reserved.

Orthopedic devices; classification for the resorbable calcium salt bone void filler device. Final rule.

PubMed

2003-06-02

The Food and Drug Administration (FDA) is classifying the resorbable calcium salt bone void filler device intended to fill bony voids or gaps of the extremities, spine, and pelvis that are caused by trauma or surgery and are not intrinsic to the stability of the bony structure into class II (special controls). Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a class II special controls guidance entitled "Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA." This action is being undertaken based on new information submitted in a classification proposal from Wright Medical Technology under the Federal Food, Drug, and Cosmetic Act as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, and the Food and Drug Administration Modernization Act of 1997.

Timeframe of socket cortication after tooth extraction: A retrospective radiographic study.

PubMed

Bertl, Kristina; Kukla, Edmund Benjamin; Albugami, Rajaa; Beck, Florian; Gahleitner, André; Stavropoulos, Andreas

2018-01-01

To assess the timeframe between tooth extraction and radiographically detectable socket cortication in humans. Two hundred and fifty patients with a CT scan ≤36 months after tooth extraction were included. First, three orthoradial multiplanar reconstruction slices, representing the major part of the extraction socket, were scored regarding the degree of bone healing as (i) healed, that is, complete/continuous cortication of the socket entrance, or (ii) non-healed. Thereafter, based on the results of all three slices, the stage of cortication of the extraction socket, as one unit, was classified as (i) non-corticated, that is, all three slices judged as non-healed, (ii) partially corticated, that is, 1 or 2 slices judged as non-healed, or (iii) completely corticated, that is, all three slices judged as healed. The possible effect of several independent parameters, that is, age, gender, timeframe between tooth extraction and CT scan, tooth type, extent of radiographic bone loss of the extracted tooth, tooth-gap type, smoking status, presence of any systemic disease, and medication intake, on cortication status was statistically evaluated. Three to 6 months after tooth extraction, 27% of the sockets were judged as non-corticated and 53% were judged as partially corticated. After 9-12 months, >80% of the sockets were corticated, while some incompletely corticated sockets were detected up to 15 months after extraction. Each additional month after tooth extraction contributed significantly to a higher likelihood of a more advanced stage of cortication, while radiographic bone loss ≥75% significantly prolonged cortication time; no other independent variable had a significant effect. The results indicate a considerably long timeframe until complete cortication of an extraction socket, that is, 3-6 months after tooth extraction 3 of 4 sockets were still not completely corticated, and only after 9-12 months, complete cortication was observed in about 80% of the sockets. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of glucose concentration on osteogenic differentiation of type II diabetes mellitus rat bone marrow-derived mesenchymal stromal cells on a nano-scale modified titanium.

PubMed

Yamawaki, I; Taguchi, Y; Komasa, S; Tanaka, A; Umeda, M

2017-08-01

Diabetes mellitus (DM) is a common disease worldwide. Patients with DM have an increased risk of losing their teeth compared with other individuals. Dental implants are a standard of care for treating partial or full edentulism, and various implant surface treatments have recently been developed to increase dental implant stability. However, some studies have reported that DM reduces osseointegration and the success rate of dental implants. The purpose of this study was to determine the effects of high glucose levels for hard tissue formation on a nano-scale modified titanium surface. Titanium disks were heated at 600°C for 1 h after treatment with or without 10 m NaOH solution. All disks were incubated with type II DM rat bone marrow-derived mesenchymal stromal cells before exposure to one of four concentrations of glucose (5.5, 8.0, 12.0 or 24.0 mm). The effect of different glucose concentrations on bone marrow-derived mesenchymal stromal cell osteogenesis and inflammatory cytokines on the nano-scale modified titanium surface was evaluated. Alkaline phosphatase activity decreased with increasing glucose concentration. In contrast, osteocalcin production and calcium deposition were significantly decreased at 8.0 mm glucose, but increased with glucose concentrations over 8.0 mm. Differences in calcium/phosphate ratio associated with the various glucose concentrations were similar to osteocalcin production and calcium deposition. Inflammatory cytokines were expressed at high glucose concentrations, but the nano-scale modified titanium surface inhibited the effect of high glucose concentrations. High glucose concentration increased hard tissue formation, but the quality of the mineralized tissue decreased. Furthermore, the nano-scale modified titanium surface increased mineralized tissue formation and anti-inflammation, but the quality of hard tissue was dependent on glucose concentration. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Depressive symptoms are not associated with forearm bone accrual during adolescence.

PubMed

Lourenço, Sara; Lucas, Raquel; da Silva, Daniele Ferreira; Ramos, Elisabete; Barros, Henrique

2014-01-01

Although depression has been associated to worst bone physical properties in adulthood, this study showed that depressive symptoms were not significantly associated to bone mineral density measured at the forearm during adolescence. Depressive conditions have been related to the reduction of bone mineral density (BMD) in adulthood. Though it is possible to hypothesize that depressive symptoms present similar effects in bone mineral accrual during adolescence, such association is poorly researched. Therefore, we aimed to study the relation between depressive symptoms and forearm BMD during adolescence. The study is based on the Epidemiological Health Investigation of Teenagers cohort that sampled adolescents born in 1990 and enrolled in public and private schools of Porto during the 2003/2004 academic year. At baseline (n = 2,160) and at 17 years of age (n = 1,716), depressive symptoms were evaluated using the Beck Depression Inventory-II (BDI-II). BMD (grams per square centimetre) was measured at the non-dominant forearm using dual-energy X-ray absorptiometry. Sex-specific crude and adjusted linear regression coefficients (β) and the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the cross-sectional and prospective associations between depressive symptoms and forearm BMD. In both sexes, in early and late adolescence, depressive symptoms presented no statistically significant association with forearm BMD (β Girls13 = 0.09, 95 % CI = -0.43 to 0.61; β Girls17 = 0.10, 95 % CI = -0.43 to 0.64; β Boys13 = -0.10, 95 % CI = -0.96 to 0.76; β Boys17 = 0.49, 95 % CI = -0.96 to 1.93). Similarly, there were no significant associations between depressive symptoms and the annual forearm BMD change during adolescence in girls and boys (β Girls_BDI-II_13-17_remained_lowest = -0.85, 95 % CI = -4.62 to 2.92 vs. β Girls_BDI-II_13-17_remained_highest = -1.87, 95 % CI = -5.06 to 1.31; β Boys_BDI-II_13-17_remained_lowest = 0.48, 95 % CI = -5.30 to 6.26 vs. β Boys_BDI-II_13-17_remained_highest = 1.36, 95 % CI = -3.25 to 5.97). Depressive symptoms, with the range of severity observed in the general adolescent population, were not associated with changes in forearm bone mineral density during adolescence. Further research based on measurements of different skeletal sites is needed in order to detect a systemic effect of depression on growing bone.

Intra-oral soft tissue expansion and volume stability of onlay bone grafts.

PubMed

Abrahamsson, Peter

2011-01-01

Insufficient regeneration of missing bone and soft-tissue may present aesthetic or functional problems in patients indicated for dental implant surgery. Several techniques such as bone grafts, bone substitutes and guided tissue regeneration (GTR) have been described to rebuild a compromised alveolar ridge. Adequate soft-tissue coverage of grafted bone and titanium-mesh is important to avoid exposure which may result in loss of the bone graft. The general aim of this thesis was to evaluate use of an osmotic tissue expander for expanding intra-oral soft tissue--creating a surplus of soft tissue-- in preparation for onlay bone grafting. An experimental rabbit model was used in studies (I), (II) and (III). In (I) an osmotic soft-tissue expander was placed bilaterally on the lateral wall of the mandible via an extra-oral approach. After two weeks of expansion the rabbits were killed and specimens were collected for histology. No inflammatory reaction and no resorbtion of the cortical bone occured. The periosteum was expanded and new bone formation was seen in the edges of the expander. In (II) and (III) the expander was placed under the periosteum in the same way as in (I): bilaterally in 13 rabbits in (II) and unilaterally in 11 rabbits in (III). After two weeks of expansion the expander was identified and removed. In (II) particulated bone was placed at the recipient site protected by a titanium mesh in one site and a bio-resorbable mesh on the other site. In (III), DBBM particles and bone particles collected from the lateral border of the mandible separated by a collagen membrane was placed at the recipient site. The graft was protected by a pre-bent titanium mesh covered by a collagen membrane. After a healing period of 3 months specimens were collected for histological and SEM examination. New bone was growing in direct contact with the titanium mesh and bio resorbable mesh. The newly formed bone had the same calcium content as the mature bone in the base of the mandible. In the clinical study (IV) 20 patients were consecutively recruited and randomised into two groups. The experimental group (ten patients) had an osmotic soft tissue expander implanted. After two weeks of expansion the expander was removed and a particulated bone graft protected by a titanium mesh and a collagen membrane was fixed to the recipient site. Titanium implants were installed after a healing period of 6 months. The patients in the reference group had a bone block grafted from the anterior ramus fixated to the recipient site with one or two titanium mini screws. Implants were installed after a healing period of 6 months. A three dimensional optical measuring device was used to measure alterations in the soft tissue profile before each surgical procedure. The three-dimensional changes were then analysed on a PC. The results from the clinical study in patients confirmed the results from the experimental rabbit studies. The osmotic tissue expander expanded the soft tissue. Expander perforations of the soft tissue occurred in two patients. The optical measurements demonstrated a positive volume gain after soft tissue expansion and bone grafting. The expanded tissue could be used to cover a bone graft. There still was a risk of mesh exposure, even after soft tissue expansion, which occurred in two patients. In both groups, implants could be installed in the grafted bone in positions that would allow the crowns to fit aesthetically into the dental arch.

Phylogenetic patterns and correlation of key structures for jumping: bone crests and cross-sectional areas of muscles in Leptodactylus (Anura, Leptodactylidae).

PubMed

Ponssa, María Laura; Fratani, Jéssica; Abdala, Virginia

2018-05-01

Anurans are characterized by their saltatory mode of locomotion, which is associated with a specific morphology. The coordinated action of the muscles and bones of the pelvic girdle is key to the transmission of the force of the hindlimbs to the axial skeleton during jumping. Two features are critical for optimal locomotory performance: the cross-sectional area of muscle and the bone crest attachment sites. The first character is a proxy of the force exerted by the muscle, whereas the crests are muscle attachments sites related to muscle force. The provisory relationship between these features has previously been identified and bone crest size can be used to infer the magnitude and, therefore, muscle force in fossils records. In this work, we explore the correlation between the cross-sectional area of essential muscles to the jumping mechanism (longissimus dorsi, extensor iliotibialis B, tenuissimus, puboischiofemoralis internus B, coccygeo-sacralis and coccygeo-iliacus) and the bone crests where these muscles are inserted (dorsal tubercle, dorsal crest and urostylar crest) in species of the genus Leptodactylus. This genus, along with other leptodactylids, exhibits a diversity of locomotor modes, including jumping, hopping, swimming and burrowing. We therefore analyzed the morphometric variation in the two features, cross-sectional area and bone crest area, expecting a correlation with different locomotor types. Our results showed: (i) a correlation between the urostylar crest and the cross-sectional area of the related muscles; (ii) that the bone crest surface area of urostyle and ilium and the cross-sectional area of the corresponding muscles can be utilized to infer locomotor faculties in leptodactylid frogs; and (iii) that the evolution of both characters demonstrates a general tendency from lower values in leptodactylid ancestors to higher values in the Leptodactylus genus. The results attest to the importance of the comparison of current ecological and phylogenetic analogues as they allow us to infer functionality and behavior in fossil and extant groups based on skeletal evidence. Phylogenetic patterns in character evolution and their correlation with locomotory types could imply that functional restrictions are also inherited in leptodactylid. © 2018 Anatomical Society.

Injectable self-gelling composites for bone tissue engineering based on gellan gum hydrogel enriched with different bioglasses.

PubMed

Douglas, Timothy E L; Piwowarczyk, Wojciech; Pamula, Elzbieta; Liskova, Jana; Schaubroeck, David; Leeuwenburgh, Sander C G; Brackman, Gilles; Balcaen, Lieve; Detsch, Rainer; Declercq, Heidi; Cholewa-Kowalska, Katarzyna; Dokupil, Agnieszka; Cuijpers, Vincent M J I; Vanhaecke, Frank; Cornelissen, Ria; Coenye, Tom; Boccaccini, Aldo R; Dubruel, Peter

2014-08-01

Hydrogels of biocompatible calcium-crosslinkable polysaccharide gellan gum (GG) were enriched with bioglass particles to enhance (i) mineralization with calcium phosphate (CaP); (ii) antibacterial properties and (iii) growth of bone-forming cells for future bone regeneration applications. Three bioglasses were compared, namely one calcium-rich and one calcium-poor preparation both produced by a sol-gel technique (hereafter referred to as A2 and S2, respectively) and one preparation of composition close to that of the commonly used 45S5 type (hereafter referred to as NBG). Incubation in SBF for 7 d, 14 d and 21 d caused apatite formation in bioglass-containing but not in bioglass-free samples, as confirmed by FTIR, XRD, SEM, ICP-OES, and measurements of dry mass, i.e. mass attributable to polymer and mineral and not water. Mechanical testing revealed an increase in compressive modulus in samples containing S2 and NBG but not A2. Antibacterial testing using biofilm-forming meticillin-resistant staphylococcus aureus (MRSA) showed markedly higher antibacterial activity of samples containing A2 and S2 than samples containing NBG and bioglass-free samples. Cell biological characterization using rat mesenchymal stem cells (rMSCs) revealed a stimulatory effect of NBG on rMSC differentiation. The addition of bioglass thus promotes GG mineralizability and, depending on bioglass type, antibacterial properties and rMSC differentiation.

Enhanced chondrogenesis of human bone marrow mesenchymal Stem Cell (BMSC) on nanofiber-based polyethersulfone (PES) scaffold.

PubMed

Mahboudi, Hossein; Kazemi, Bahram; Soleimani, Masoud; Hanaee-Ahvaz, Hana; Ghanbarian, Hossein; Bandehpour, Mojgan; Enderami, Seyed Ehsan; Kehtari, Mousa; Barati, Ghasem

2018-02-15

Mesenchymal stem cells (MSC) from bone marrow hold great potential as a cell source for cartilage repair. The objective of our study was differentiation of MSC toward chondrocyte by using Nanofiber-based polyethersulfone (PES) scaffold and also enhanced chondrogenic differentiation of BMSC in vitro. MSCs were harvested from bone marrow of human and PES scaffold was fabricated via Electrospinning. The isolated cells were cultured on the PES scaffold and scaffold free method. After 21days, Real-time PCR was performed to evaluate the cartilage-specific genes in the mRNA levels. Also, in order to confirm our results, we have done immunocytochemistry and SEM imaging. Flowcytometry confirmed the nature of the isolated adherent cells. Immunocytochemistry and SEM imaging confirmed the differentiation of MSC toward chondrocyte. Also, real time PCR showed a significant increased gene expression of collagen type II and aggrecan on the PES scaffold method when compared to the mRNA levels measured in scaffold free method. Down regulation of Collagen type I was observed in PES scaffold compared to scaffold free at day 21. Also, both methods showed a similar pattern of expression of SOX9. Our results showed that PES scaffold maintains BMSC proliferation and differentiation, and can significantly enhance chondrogenic differentiation of BMSC. PES scaffold seeded BMSC showed the highest capacity for differentiation into chondrocyte-like cells. Copyright © 2017 Elsevier B.V. All rights reserved.

An individualised risk-adapted protocol of pre- and post transplant zoledronic acid reduces bone loss after allogeneic stem cell transplantation: results of a phase II prospective trial.

PubMed

Grigg, A; Butcher, B; Khodr, B; Bajel, A; Hertzberg, M; Patil, S; D'Souza, A B; Ganly, P; Ebeling, P; Wong, E

2017-09-01

Bone loss occurs frequently following allogeneic haematopoietic stem cell transplantation (alloSCT). The Australasian Leukaemia and Lymphoma Group conducted a prospective phase II study of pretransplant zoledronic acid (ZA) and individualised post-transplant ZA to prevent bone loss in alloSCT recipients. Patients received ZA 4 mg before conditioning. Administration of post-transplant ZA from days 100 to 365 post alloSCT was determined by a risk-adapted algorithm based on serial bone density assessments and glucocorticoid exposure. Of 82 patients enrolled, 70 were alive and without relapse at day 100. A single pretransplant dose of ZA prevented femoral neck bone loss at day 100 compared with baseline (mean change -2.6±4.6%). Using the risk-adapted protocol, 42 patients received ZA between days 100 and 365 post alloSCT, and this minimised bone loss at day 365 compared with pretransplant levels (mean change -2.9±5.3%). Femoral neck bone loss was significantly reduced in ZA-treated patients compared with historical untreated controls at days 100 and 365. This study demonstrates that a single dose of ZA pre-alloSCT prevents femoral neck bone loss at day 100 post alloSCT, and that a risk-adapted algorithm is able to guide ZA administration from days 100 to 365 post transplant and minimise further bone loss.

Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

PubMed

Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

2016-09-01

Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative immunolocalisation of perlecan with collagen II and aggrecan in human foetal, newborn and adult ovine joint tissues demonstrates perlecan as an early developmental chondrogenic marker.

PubMed

Smith, Susan M; Shu, Cindy; Melrose, James

2010-09-01

We undertook a comparative immunolocalisation study on type II collagen, aggrecan and perlecan in a number of 12- to 14-week-old human foetal and postnatal (7-19 months) ovine joints including finger, toe, knee, elbow, hip and shoulder. This demonstrated that perlecan followed a virtually identical immunolocalisation pattern to that of type II collagen in the foetal tissues, but a slightly divergent localisation pattern in adult tissues. Aggrecan was also localised in the cartilaginous joint tissues, which were clearly delineated by toluidine blue staining and the type II collagen immunolocalisations. It was also present in the capsular joint tissues and in ligaments and tendons in the joint, which stained poorly or not at all with toluidine blue. In higher power microscopic views, antibodies to perlecan also stained small blood vessels in the synovial lining tissues of the joint capsule; however, this was not discernable in low power macroscopic views where the immunolocalisation of perlecan to pericellular regions of cells within the cartilaginous rudiments was a predominant feature. Perlecan was also evident in small blood vessels in stromal connective tissues associated with the cartilage rudiments and with occasional nerves in the vicinity of the joint tissues. Perlecan was expressed by rounded cells in the enthesis attachment points of tendons to bone and in rounded cells in the inner third of the meniscus, which stained prominently with type II collagen and aggrecan identifying the chondrogenic background of these cells and local compressive loads. Flattened cells within the tendon and in the surface laminas of articular cartilages and the meniscus did not express perlecan. Collected evidence presented herein, therefore, indicates that besides being a basement membrane component, perlecan is also a marker of chondrogenic cells in prenatal cartilages. In postnatal cartilages, perlecan displayed a pericellular localisation pattern rather than the territorial or interterritorial localisation it displayed in foetal cartilages. This may reflect processing of extracellular perlecan presumably as a consequence of intrinsic biomechanical loading on these tissues or to divergent functions for perlecan and type II collagen in adult compared to prenatal tissues.

Implant Supported Distal Extension over Denture Retained by Two Types of Attachments. A Comparative Radiographic Study by Cone Beam Computed Tomography

PubMed Central

Mahrous, Ahmed I; Aldawash, Hussien A; Soliman, Tarek A; Banasr, Fahad H; Abdelwahed, Ahmed

2015-01-01

Background: This study was conducted to compare and evaluate the effect of two different attachments (locator attachment and ball and socket [B&S] attachment) on implants and natural abutments supporting structures, in cases of limited inter-arch spaces in mandibular Kennedy Class I implant supported removable partial over dentures by measuring the bone height changes through the cone beam radiographic technology. Materials and Methods: Two implants were positioned in the first or second molar area following the two-stage surgical protocol. Two equal groups were divided ten for each: Group I: Sides were the placed implants restored by the locator attachment. Group II: The other sides, implants were restored by B&S attachment. Evaluation of the implants and main abutments supporting structures of each group was done at the time of removable partial over denture insertion, 6, 12 and 18 months by measuring the bone height changes using cone beam computed tomography. Results: Implants with locator attachment showed marginal bone height better effects on implants and main abutments supporting structures. Conclusion: Implants restored by locator attachment shows better effects on bone of both main natural abutments and implant than those restored with ball and socket. PMID:26028894

[Toxic phosphorous osteonecrosis of facial bones among drug addicts to desomorphine and pervitin. Part II].

PubMed

Basin, E M; Medvedev, Yu A

2015-01-01

Article describes literature review of "atypical" osteomyelitis--osteonecrosis of facial bones among addicts to synthetic narcotics desomorphine and pervitin, different comorbidities, treatment strategy and prognosis were outlined

Changes in Bone Alkaline Phosphatase and Procollagen Type-1 C-Peptide after Static and Dynamic Exercises

ERIC Educational Resources Information Center

Kubo, Keitaro; Yuki, Kazuhito; Ikebukuro, Toshihiro

2012-01-01

We investigated the effects of two types of nonweight-bearing exercise on changes in bone-specific alkaline phosphatase (BAP) and pro-collagen type 1 C-peptide (P1P). BAP is a specific marker of bone synthesis, whereas P1P reflects synthesis of type 1 collagen in other organs as well as bone. Eight participants performed static and dynamic…

Correlation Between Resonance Frequency Analysis and Bone Quality Assessments at Dental Implant Recipient Sites.

PubMed

Fu, Min-Wen; Fu, Earl; Lin, Fu-Gong; Chang, Wei-Jeng; Hsieh, Yao-Dung; Shen, E-Chin

To evaluate whether primary implant stability could be used to predict bone quality, the association between the implant stability quotient (ISQ) value and the bone type at the implant site was evaluated. Ninety-five implant sites in 50 patients were included. Bone type (categorized by Lekholm and Zarb) at the implant site was initially assessed using presurgical dental radiography. During the preparation of the implant site, a bone core specimen was carefully obtained. The bone type was assessed by tactile sensation during the drilling operation, according to the Misch criteria. The primary stability of the inserted implant was evaluated by resonance frequency analysis (RFA). The ISQ value was recorded. The bone core specimen was then examined by stereomicroscopy or microcomputed tomography (micro-CT), and the bone type was determined by the surface characteristics of the specimen, based on Lekholm and Zarb classification. Agreement between the bone quality assessed by the four methods (ie, presurgical radiography, tactile sensation, stereomicroscopy, and micro-CT) was tested by Cohen's kappa statistics, whereas the association between the ISQ value and the bone type was evaluated by the generalized linear regression model. The mean ISQ score was 72.6, and the score was significantly influenced by the maxillary or mandibular arch (P = .001). The bone type at the implant sites varied according to the assessment method. However, a significant influence of the arch was repeatedly noted when using radiography or tactile sensation. Among the four bone-quality assessment methods, a weak agreement existed only between stereomicroscopy and micro-CT, especially in the maxilla (κ = 0.469). A negative association between the ISQ value and the bone type assessed by stereomicroscopy or by micro-CT was significant in the maxilla, but not in the mandible, after adjustments for sex, age, and right/left side (P = .013 and P = .027 for stereomicroscopy and micro-CT, respectively). The ISQ value was weakly associated with the bone type when assessed by stereomicroscopy or micro-CT in the maxilla. Caution is necessary if RFA is used as a tool to evaluate bone quality at the implant site, especially in the mandible.

[Effect of different bone cement dispersion types in the treatment of osteoporotic vertebral compression fracture].

PubMed

Zhao, Yong-Sheng; Li, Qiang; Li, Qiang; Zheng, Yan-Ping

2017-05-25

To observe different bone cement dispersion types of PVP, PKP and manipulative reduction PVP and their effects in the treatment of senile osteoporotic vertebral compression fractures and the bone cement leakage rate. The clinical data of patients with osteoporotic vertebral compression fractures who underwent unilateral vertebroplasty from January 2012 to January 2015 was retrospectively analyzed. Of them, 56 cases including 22 males and 34 females aged from 60 to 78 years old were treated by PVP operation; Fouty-eight cases including 17 males and 31 females aged from 61 to 79 years old were treated by PKP operation; Forty-three cases including 15 males and 28 females aged from 60 to 76 years old were treated by manipulative reduction PVP operation. AP and lateral DR films were taken after the operation; the vertebral bone cement diffusion district area and mass district area were calculated with AutoCAD graphics processing software by AP and lateral DR picture, then ratio(K) of average diffusion area and mass area were calculated, defining K<50% as mass type, 50%<=K<=100% as mixed type and K>100% as diffusion type. Different bone cement dispersion types of PVP, PKP and manipulative reduction PVP operation were analyzed. According to bone cement dispersion types, patients were divided into diffusion type, mixed type and mass type groups.Visual analogue scale (VAS), vertebral body compression rate, JOA score and bone cement leakage rate were observed. All patients were followed up for 12-24 months with an average of 17.2 months. There was significant difference in bone cement dispersion type among three groups ( P <0.05). The constituent ratio of diffusion type, mixed type and mass type in PVP operation was 46.43%, 35.71%, 17.86%, in PKP was 16.67%, 37.50% , 45.83%, and in manipulative reduction PVP was 37.21%, 44.19% and 18.60%, respectively. PVP operation and manipulative reduction PVP were mainly composed of diffusion type and mixed type, while PKP was mainly composed of mass type and mixed type. There was no significant difference in VAS score, JOA score and bone cement leakage rate among three groups. There was statistically significant difference in postoperative vertebral body compression rate among three bone cement dispersion types( P <0.05), postoperative vertebral body compression rate in diffusion type group at 24 h postoperatively and final follow-up was (17.31±5.06)% and(18.58±4.91)%, respectively. In mixed type group, it was(14.21±5.15)% and(14.59±5.07)%, respectively. In mass type group, it was(13.89±5.02)% and(14.28±4.94)%, respectively. Bone cement dispersion type is different in PVP, PKP and manipulative reduction PVP operation. The bone cement dispersion of mass type and mixed type to recovery of compressed vertebral body is better than diffusion type, and there is no obvious difference in clinical effect in different bone cement dispersion type early and middle term.

Immuno-histopathologic evaluation of Drynaria fortunei rhizome extract in the management of grade II furcation defects in a canine model.

PubMed

Afifi, Marwa M; Kotry, Gehan S; El-Kimary, Gillan I; Youssef, Hayat A

2018-06-06

Management of furcation defects is still a challenging subject in periodontal therapy. Drynaria fortunei (Df) is a common type of traditional Chinese herb in the area of orthopedics and traumatology. In- vitro and tissue engineering studies have shown that Df induces osteoblastic proliferation and promotes the differentiation of human periodontal ligament cells. This study investigated the management of grade II furcation defects in dogs using guided tissue regeneration (GTR) and Df granules mixed with β- tri-calcium phosphate alloplast (β- TCP). Sixteen grade II critical -sized furcation defects were surgically created in four mongrel dogs: Eight defects were treated with GTR and Df granules mixed with (β- TCP) alloplast served as the experimental group, while the other eight were managed with GTR and alloplast, served as control. Dogs were sacrificed at four and eight weeks and the premolars were processed for the evaluation of treatment outcome including; osteoblastic count (OC), cementum layer thickness (CLT), percentage of collagen in bone matrix (CBM), and alkaline phosphatase (ALP) immunoreaction. Experimental group treated with Df showed a significant increase (P < 0.001) in the values of OC, CLT, CBM, and ALP immunoreacitivity when compared to control at four and eight weeks after treatment. Df demonstrated increased regeneration and bone-formation when used in the treatment of furcation defects in a canine model. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

PERFORMANCE OF CONVENTIONAL PCRs BASED ON PRIMERS DIRECTED TO NUCLEAR AND MITOCHONDRIAL GENES FOR THE DETECTION AND IDENTIFICATION OF Leishmania spp.

PubMed Central

LOPES, Estela Gallucci; GERALDO, Carlos Alberto; MARCILI, Arlei; SILVA, Ricardo Duarte; KEID, Lara Borges; OLIVEIRA, Trícia Maria Ferreira da Silva; SOARES, Rodrigo Martins

2016-01-01

In visceral leishmaniasis, the detection of the agent is of paramount importance to identify reservoirs of infection. Here, we evaluated the diagnostic attributes of PCRs based on primers directed to cytochrome-B (cytB), cytochrome-oxidase-subunit II (coxII), cytochrome-C (cytC), and the minicircle-kDNA. Although PCRs directed to cytB, coxII, cytC were able to detect different species of Leishmania, and the nucleotide sequence of their amplicons allowed the unequivocal differentiation of species, the analytical and diagnostic sensitivity of these PCRs were much lower than the analytical and diagnostic sensitivity of the kDNA-PCR. Among the 73 seropositive animals, the asymptomatic dogs had spleen and bone marrow samples collected and tested; only two animals were positive by PCRs based on cytB, coxII, and cytC, whereas 18 were positive by the kDNA-PCR. Considering the kDNA-PCR results, six dogs had positive spleen and bone marrow samples, eight dogs had positive bone marrow results but negative results in spleen samples and, in four dogs, the reverse situation occurred. We concluded that PCRs based on cytB, coxII, and cytC can be useful tools to identify Leishmania species when used in combination with automated sequencing. The discordance between the results of the kDNA-PCR in bone marrow and spleen samples may indicate that conventional PCR lacks sensitivity for the detection of infected dogs. Thus, primers based on the kDNA should be preferred for the screening of infected dogs. PMID:27253743

Human Bone-Forming Chondrocytes Cultured in the Hydrodynamic Focusing Bioreactor Retain Matrix Proteins: Similarities to Spaceflight Results

NASA Technical Reports Server (NTRS)

Duke, P. J.; Hecht, J.; Montufar-Solis, D.

2006-01-01

Fracture healing, crucial to a successful Mars mission, involves formation of a cartilaginous fracture callus which differentiates, mineralizes, ossifies and remodels via the endochondral process. Studies of spaceflown and tailsuspended rats found that, without loading, fracture callus formation and cartilage differentiation within the callus were minimal. We found delayed differentiation of chondrocytes within the rat growth plate on Cosmos 1887, 2044, and Spacelab 3. In the current study, differentiation of human bone-forming chondrocytes cultured in the hydrodynamic focusing bioreactor (HFB) was assessed. Human costochondral chondrocytes in suspension were aggregated overnight, then cultured in the HFB for 25 days. Collagen Type II, aggrecan and unsulfated chondroitin were found extracellularly and chondroitin sulfates 4 and 6 within the cell. Lack of secretion was also found in pancreatic cells of spaceflown rats, and in our SL3 studies. The HFB can be used to study cartilage differentiation in simulated microgravity.

Glycemic control and alveolar bone loss progression in type 2 diabetes.

PubMed

Taylor, G W; Burt, B A; Becker, M P; Genco, R J; Shlossman, M

1998-07-01

This study tested the hypothesis that the risk for alveolar bone loss is greater, and bone loss progression more severe, for subjects with poorly controlled (PC) type 2 diabetes mellitus (type 2 DM) compared to those without type 2 DM or with better controlled (BC) type 2 DM. The PC group had glycosylated hemoglobin (HbA1) > or = 9%; the BC group had HbA1 < 9%. Data from the longitudinal study of the oral health of residents of the Gila River Indian Community were analyzed. Of the 359 subjects, aged 15 to 57 with less than 25% radiographic bone loss at baseline, 338 did not have type 2 DM, 14 were BC, and 7 were PC. Panoramic radiographs were used to assess interproximal bone level. Bone scores (scale 0-4) corresponding to bone loss of 0%, 1% to 24%, 25% to 49%, 50% to 74%, or > or = 75% were used to identify the worst bone score (WBS) in the dentition. Change in worst bone score at follow-up, the outcome, was specified on a 4-category ordinal scale as no change, or a 1-, 2-, 3-, or 4-category increase over baseline WBS (WBS1). Poorly controlled diabetes, age, calculus, time to follow-up examination, and WBS1 were statistically significant explanatory variables in ordinal logistic regression models. Poorly controlled type 2 DM was positively associated with greater risk for a change in bone score (compared to subjects without type 2 DM) when the covariates were included in the model. The cumulative odds ratio (COR) at each threshold of the ordered response was 11.4 (95% CI = 2.5, 53.3). When contrasted with subjects with BC type 2 DM, the COR for those in the PC group was 5.3 (95% CI = 0.8, 53.3). The COR for subjects with BC type 2 DM was 2.2 (95% CI = 0.7, 6.5), when contrasted to those without type 2 DM. These results suggest that poorer glycemic control leads to both an increased risk for alveolar bone loss and more severe progression over those without type 2 DM, and that there may be a gradient, with the risk for bone loss progression for those with better controlled type 2 DM intermediate to the other 2 groups.

Evaluation of lipid peroxidation and antioxidant defense mechanisms in the bone of rats in conditions of separate and combined administration of vanadium (V) and magnesium (Mg).

PubMed

Ścibior, Agnieszka; Gołębiowska, Dorota; Adamczyk, Agnieszka; Kurus, Joanna; Staniszewska, Magdalena; Sadok, Ilona

2018-03-25

The impact of vanadium (V) and magnesium (Mg) applied as sodium metavanadate (SMV, 0.125 mg V/ml) and magnesium sulfate (MS, 0.06 mg Mg/ml) on oxidative stress markers in bone of male Wistar rats was investigated. Some of them were also measured in the liver, e.g. l-ascorbic acid (hepatic L-AA). Additionally, relationships between selected indices determined in bone were examined. SMV alone (Group II) did not significantly alter the level of TBARS and the activity of SOD, compared with the control (Group I), but it slightly reduced the GR activity (by 13%) and the L-AA level (by 15.5%). It also markedly lowered the activity of CAT and GPx (by 34% and 29%), and to some degree elevated the activity of GST (by 16%) and the hepatic L-AA level (by 119%). MS alone (Group III) decreased the TBARS level (by 49%), slightly lowered the L-AA concentration (by 14%), and reduced the SOD, GPx, and GR activities (by 31%, 40%, and 28%), but did not change the activity of CAT, compared with the control. Additionally, it elevated the GST activity (by 56%) and the hepatic L-AA level (by 40%). In turn, the SMV + MS combination (Group IV) reduced the TBARS level (by 38%) and the SOD, CAT, GPx, and GR activities (by 61%, 58%, 72%, and 40%) but elevated the GST activity (by 66%), compared with the control. The activity of SOD and GPx in the rats in Group IV was also reduced, compared with Group II (by 61% and 61%) and Group III (by 44% and 54%). In turn, the activities of CAT and GR were decreased, compared with Group III (by 55%) and Group II (by 31%), and the L-AA level was lowered, in comparison with Groups II and III (by 53% and 54%). Further, the concentration of V in the bone of rats in Groups II and IV increased, whereas the concentration of Mg decreased, compared with Groups I and III, in which the V and Mg levels dropped and were not altered, respectively, compared with Group I. The total content of Fe in the bone of rats in Groups II and IV increased, compared with Group III, in which the total Fe content did not change, compared with Group I. In turn, the total bone Cu content significantly decreased in the rats in Groups III and IV, compared with Groups I and II, whereas the total Zn content and the Ca concentration did not change markedly. The results provided evidence that the concentration of V used as SMV did not enhance LPO in bone, whereas Mg, at the selected level, markedly reduced LPO in this tissue. On the other hand, both elements administered separately and in combination disrupted the antioxidant defense mechanisms and homeostasis of some metals in bone tissue, which consequently may have contributed to disturbances in the balance in the activities of osteoblastic and osteoclastic cells, and thereby negatively affected bone health. Copyright © 2018 Elsevier B.V. All rights reserved.

[Correlation analysis of bone marrow edema degree and serum inflammatory factors change with knee joint pain symptoms in patients with bone contusion around the knee joint].

PubMed

Li, Songiun; An, Rongze; Wang, Zhaojie; Kuang, Lipeng; Tan, Weiyuan; Fang, Cunxun

2014-05-01

To explore the correlation between the degree of bone marrow edema (BME) and the content change of tumor necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 3 (MMP-3) and the knee pain symptoms in patients with bone contusion around the knee joint. Thirty patients (30 knees) of bone contusion around the knee joint were chosen as the trial group between October 2009 and April 2012. According to visual analogue scale (VAS), 30 patients were divided into mild group (10 cases), moderate group (10 cases), and severe group (10 cases); according to MRI morphological changes, the patients were divided into type I group (12 cases), type II group (11 cases), and type III group (7 cases). Ten patients (10 knees) with soft tissue injury of the knee were chosen as control group. No significant difference was found (P > 0.05) in gender, age, causes, side, and admission time after injury between 2 groups. The serum contents of MMP-3 and TNF-alpha were detected and statistically analysed between different degrees of pain groups and between different degrees of BME groups. Correlation was analysed between BME and inflammatory factor changes and VAS score. The MMP-3 and TNF-alpha contents in trial group [(29.580 +/- 6.870) (microg/L and (23.750 +/- 7.096) ng/L] were significantly higher than those in control group [(8.219 +/- 1.355) microg/L and (6.485 +/- 1.168) ng/L] (t = 9.686, P = 0.000; t = 7.596, P =0.000). The MMP-3 and TNF-alpha contents in patients with different degrees of pain and BME were significantly higher than those in patients of control group (P < 0.05), and significant difference was found between patients with different degrees of pain (P < 0.05), but no significant difference between patients with different degrees of BME (P > 0.05). Multiple linear regression analysis showed that TNF-alpha content was significantly correlated with VAS score (P = 0.000). Knee pain symptoms are not related to the degree of BME in patients with bone contusion around the knee joint. Inflammatory factor TNF-alpha content is the main influence factor of knee joint pain symptoms.

Observations on the bony bridging of the jugular foramen in man.

PubMed Central

Dodo, Y

1986-01-01

The anatomical nature and pattern of incidence of bony bridging of the jugular foramen was investigated using 64 fetal crania aged nine months to term and 222 adult crania of Japanese. In addition, the region of the jugular foramen of an adult cadaver was carefully dissected in order to clarify the relationship between the cranial nerves passing through the jugular foramen and the intrajugular processes of the jugular foramen. The general conclusions concerning the anatomical nature of the bony bridging of the jugular foramen were as follows. (1) The intrajugular process of the temporal bone is situated posterior to the triangular depression (as described in Gray's Anatomy) of the petrous part. (2) The bony bridging of the jugular foramen is established by the contact of the intrajugular process of the temporal bone with the bony process of the occipital bone projecting either from just above the hypoglossal canal (Type I) or from posterior to the hypoglossal canal (Type III). (3) If both the processes of the occipital bone reach the intrajugular process of the temporal bone simultaneously, the jugular foramen is divided into three compartments. (4) In the case of Type I bridging, the anteromedial compartment transmits the glossopharyngeal nerve, while the posterolateral compartment gives passage to the vagus nerve, the accessory nerve and the internal jugular vein. (5) In the case of Type II bridging, the anteromedial compartment contains the glossopharyngeal, vagus and accessory nerves, and the posterolateral compartment transmits the internal jugular vein. (6) When tripartite division of the jugular foramen occurs, the anteromedial compartment transmits the glossopharyngeal nerve, the middle compartment contains the vagus and accessory nerves, and the posterolateral compartment transmits the internal jugular vein. Concerning the pattern of incidence of jugular foramen bridging in the Japanese fetal and adult cranial series, this is similar to that of the bony bridging of the hypoglossal canal. The fact that almost all the cases of bridging of the jugular foramen are already established by the end of fetal development must serve as a strong indication that this trait can be used effectively for anthropological population studies. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 11 PMID:3693042

Three-dimensional assessment of crestal bone levels at titanium implants with different abutment microstructures and insertion depths using micro-computed tomography.

PubMed

Becker, Kathrin; Klitzsch, Inka; Stauber, Martin; Schwarz, Frank

2017-06-01

To (i) assess the impact of insertion depth and abutment microstructure on the three-dimensional crestal bone-level changes at endosseous titanium implant using μCT and computerized image processing and (ii) to correlate the findings with previously reported histology. Titanium implants (conical abutment connection) were inserted in each hemimandible of n = 6 foxhounds with the implant shoulder (IS) located either in epicrestal (0 mm), supracrestal (+1 mm) or subcrestal (-1 mm) positions and randomly (split-mouth design) connected with machined or partially micro-grooved healing abutments. At 20 weeks, the tissue biopsies were processed for μCT and histological (HI) analyses. The volumetric dehiscence profile around the implants was computed as distance between the implant shoulder (IS) and the most coronal bone-to-implant contact (CBI) using MATLAB. The respective buccal and oral values were averaged, and agreement with the respective IS-CBI scores from HI was assessed using Bland-Altman plots. A median net bone gain was observed for supracrestal insertion depths at both abutment types, but lower bounds of the 75% quartile experienced net bone losses. Epicrestal and subcrestal insertion depths were linked to slight bone losses, and the buccal and oral dehiscences were smaller compared to supracrestal positioning. Bland-Altman plots yielded a moderate agreement of IS-CBI values measured with μCT and HI. The novel image processing method allowed reliable evaluations and pointed to a direct impact of insertion depths on crestal bone-level changes. Additionally, it demonstrated that HI morphometry crucially depends on the chosen cutting position. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expression of the genes for insulin-like growth factors and their receptors in bone during skeletal growth

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Harris, J.; Halloran, B. P.; Roberts, C. T.; Leroith, D.; Morey-Holton, E.

1994-01-01

Insulin-like growth factors (IGF) are important regulators of skeletal growth. To determine whether the capacity to produce and respond to these growth factors changes during skeletal development, we measured the protein and mRNA levels for IGF-I, IGF-II, and their receptors (IGF-IR and IGF-IIR, respectively) in the tibia and femur of rats before and up to 28 mo after birth. The mRNA levels remained high during fetal development but fell after birth, reaching a nadir by 3-6 wk. This fall was most pronounced for IGF-II and IGF-IIR mRNA and least pronounced for IGF-I mRNA. However, after 6 wk, both IGF-I and IGF-IR mRNA levels recovered toward the levels observed at birth. In the prenatal bones, the signals for the mRNAs of IGF-II and IGF-IIR were stronger than the signals for the mRNAs of IGF-I and IGF-IR, although the content of IGF-I was three- to fivefold greater than that of IGF-II. IGF-II levels fell postnatally, whereas the IGF-I content rose after birth such that the ratio IGF-I/IGF-II continued to increase with age. We conclude that, during development, rat bone changes its capacity to produce and respond to IGFs with a progressive trend toward the dominance of IGF-I.

Mesenchymal stem cell differentiation in an experimental cartilage defect: restriction of hypertrophy to bone-close neocartilage.

PubMed

Steck, Eric; Fischer, Jennifer; Lorenz, Helga; Gotterbarm, Tobias; Jung, Martin; Richter, Wiltrud

2009-09-01

Mesenchymal stem cells (MSCs) are promising for the treatment of articular cartilage defects; however, common protocols for in vitro chondrogenesis induce typical features of hypertrophic chondrocytes reminiscent of endochondral bone formation. Aim of the study was to compare chondrogenic differentiation of MSCs in vitro and in vivo in experimental full-thickness cartilage defects, asking whether MSCs can differentiate into collagen type X-negative chondrocytes in an orthotopic environment. Cartilage defects in knees of minipigs were covered with a collagen type I/III membrane, and half of them received transplantation of expanded autologous MSCs. At 1, 3, and 8 weeks, morphological and molecular aspects of repair were assessed. The orthotopic environment triggered a spatially organized repair tissue with upper fibrous, intermediate chondrogenic, and low layer hypertrophic differentiation of cells and a trend to more safranin-O and collagen type II-positive samples after MSC transplantation at 8 weeks. Compared to in vitro chondrogenesis, significant lower COL10A1/COL2A1 and MMP13/COL2A1 ratios were obtained for in vivo differentiation. This indicates that, as opposed to in vitro chondrogenic induction of MSCs, the in vivo signaling molecules and biomechanical stimuli provide an appropriate environment for progenitor cells to differentiate into collagen type X-negative chondrocytes. Thus, until better in vitro induction protocols become available for chondrogenesis of MSCs, their predifferentiation before transplantation may be unfavorable.

[Clinical studies on lower urinary tract injury].

PubMed

Tanaka, M; Ozono, S; Takashima, K; Yoshida, K; Hirao, Y; Okajima, E; Kaneko, Y; Tabata, S; Yoshida, K; Moriya, A

1997-01-01

A total of 61 patients with lower urinary tract injuries were treated at Nara Medical University and its affiliated hospitals, between January 1985 and June 1995. There were 9 patients with bladder injuries and 52 patients with urethral injuries. The main cause of bladder injury was a traffic accident sustained in 4 patients (44.5%) and that of urethral injury was an occupational accident sustained in 27 cases (51.9%). The major associated injuries were a bone fracture seen in 45 patients (73.8%) and an intrascrotal hematoma seen in 28 patients (45.9%). Posterior urethral injuries associated with pelvic bone fractures were classified into 3 types according to the classification reported by Colapinto et al.; 8 patients (32.0%) into Type I, 8 (32.0%) into Type II and 9 (36.0%) into Type III. Of the 25 patients with posterior urethral injuries, 8 (32.0%) underwent immediate surgical treatment, 12 (48.0%) underwent initial cystostomies and delayed surgical treatment and 5 (20.0%) received indwelling of urethral catheters. Postoperative complications of urethral injury included urethral stricture in 30 patients (57.7%), incontinence in 3 (5.8%) and impotence in 3 (5.8%). A significant relationship between the duration of cystostomy and the incidence of postoperative urethral stricture was observed in our patients. Therefore at least three weeks of cystostomy will be necessary in the management of patients with complicated urethral injuries.

Engraftment Efficiency after Intra-Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model.

PubMed

Lange, Sandra; Steder, Anne; Killian, Doreen; Knuebel, Gudrun; Sekora, Anett; Vogel, Heike; Lindner, Iris; Dunkelmann, Simone; Prall, Friedrich; Murua Escobar, Hugo; Freund, Mathias; Junghanss, Christian

2017-02-01

An intra-bone marrow (IBM) hematopoietic stem cell transplantation (HSCT) is assumed to optimize the homing process and therefore to improve engraftment as well as hematopoietic recovery compared with conventional i.v. HSCT. This study investigated the feasibility and efficacy of IBM HSCT after nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received IBM HSCT of either density gradient (IBM-I, n = 7) or buffy coat (IBM-II, n = 6) enriched bone marrow cells. An historical i.v. HSCT cohort served as control. Before allogeneic HSCT experiments were performed, we investigated the feasibility of IBM HSCT by using technetium-99m marked autologous grafts. Scintigraphic analyses confirmed that most IBM-injected autologous cells remained at the injection sites, independent of the applied volume. In addition, cell migration to other bones occurred. The enrichment process led to different allogeneic graft volumes (IBM-I, 2 × 5 mL; IBM-II, 2 × 25 mL) and significantly lower counts of total nucleated cells in IBM-I grafts compared with IBM-II grafts (1.6 × 10 8 /kg versus 3.8 × 10 8 /kg). After allogeneic HSCT, dogs of the IBM-I group showed a delayed engraftment with lower levels of donor chimerism when compared with IBM-II or to i.v. HSCT. Dogs of the IBM-II group tended to reveal slightly faster early leukocyte engraftment kinetics than intravenously transplanted animals. However, thrombocytopenia was significantly prolonged in both IBM groups when compared with i.v. HSCT. In conclusion, IBM HSCT is feasible in a nonmyeloablative HSCT setting but failed to significantly improve engraftment kinetics and hematopoietic recovery in comparison with conventional i.v. HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Prokaryotic expression of bone sialoprotein and identification of casein kinase II phosphorylation sites.

PubMed

Saad, Fawzy A; Salih, Erdjan; Wunderlich, Livius; Flückiger, Rudolf; Glimcher, Melvin J

2005-07-29

Bone sialoprotein is an extracellular noncollagenous acidic protein that plays a role in bone mineralization and remodeling. Its expression is restricted to mineralized tissues and is subjected to variety of posttranslational modifications including phosphorylation and glycosylation. We have expressed the full-length and half domains of bovine bone sialoprotein in a prokaryotic system and identified the phosphorylation sites of casein kinase II. The N-terminal automated solid-phase sequencing defined four phosphorylated peptides: residues 28-38 (LEDS(P)EENGVFK), 51-86 (FYPELKRFAVQSSS(P)DS(P)S(P)EENGNGDS(P)S(P)EEEEEEEETS(P)), 151-165 (EDES(P)DEEEEEEEEEE), and 295-305 (GRGYDS(P)YDGQD). Nine phosphoserines were identified within the four peptides. Seven of them were in the N-terminus (S31, S64, S66, S67, S75, S76, and S86) and two were in the C-terminus (S154 and S300) of the protein.

Unraveling hominin behavior at another anthropogenic site from Olduvai Gorge (Tanzania): new archaeological and taphonomic research at BK, Upper Bed II.

PubMed

Domínguez-Rodrigo, M; Mabulla, A; Bunn, H T; Barba, R; Diez-Martín, F; Egeland, C P; Espílez, E; Egeland, A; Yravedra, J; Sánchez, P

2009-09-01

New archaeological excavations and research at BK, Upper Bed II (Olduvai Gorge, Tanzania) have yielded a rich and unbiased collection of fossil bones. These new excavations show that BK is a stratified deposit formed in a riverine setting close to an alluvial plain. The present taphonomic study reveals the second-largest collection of hominin-modified bones from Olduvai, with abundant cut marks found on most of the anatomical areas preserved. Meat and marrow exploitation is reconstructed using the taphonomic signatures left on the bones by hominins. Highly cut-marked long limb shafts, especially those of upper limb bones, suggest that hominins at BK were actively engaged in acquiring small and middle-sized animals using strategies other than passive scavenging. The exploitation of large-sized game (Pelorovis) by Lower Pleistocene hominins, as suggested by previous researchers, is supported by the present study.

Contour changes in human alveolar bone following tooth extraction of the maxillary central incisor.

PubMed

Li, Bei; Wang, Yao

2014-12-01

The purpose of this study was to apply cone-beam computed tomography (CBCT) to observe contour changes in human alveolar bone after tooth extraction of the maxillary central incisor and to provide original morphological evidence for aesthetic implant treatment in the maxillary anterior area. Forty patients were recruited into the study. Each patient had two CBCT scans (CBCT I and CBCT II), one taken before and one taken three months after tooth extraction of maxillary central incisor (test tooth T). A fixed anatomic reference point was used to orient the starting axial slice of the two scans. On three CBCT I axial slices, which represented the deep, middle, and shallow layers of the socket, labial and palatal alveolar bone widths of T were measured. The number of sagittal slices from the start point to the pulp centre of T was recorded. On three CBCT II axial slices, the pulp centres of extracted T were oriented according to the number of moved sagittal slices recorded in CBCT I. Labial and palatal alveolar bone widths at the oriented sites were measured. On the CBCT I axial slice which represented the middle layer of the socket, sagittal slices were reconstructed. Relevant distances of T on the sagittal slice were measured, as were the alveolar bone width and tooth length of the opposite central incisor. On the CBCT II axial slice, which represented the middle layer of the socket, relevant distances recorded in CBCT I were transferred on the sagittal slice. The height reduction of alveolar bone on labial and palatal sides was measured, as were the alveolar bone width and tooth length of the opposite central incisor at the oriented site. Intraobserver reliability assessed by intraclass correlation coefficients (ICCs) was high. Paired sample t-tests were performed. The alveolar bone width and tooth length of the opposite central incisor showed no statistical differences (P<0.05). The labial alveolar bone widths of T at the deep, middle, and shallow layers all showed statistical differences. However, no palatal alveolar bone widths showed any statistical differences. The width reduction of alveolar bone was 1.2, 1.6, and 2.7 mm at the deep, middle, and shallow layers, respectively. The height reduction of alveolar bone on labial and palatal sides of T both showed statistical differences, which was 1.9 and 1.1 mm, respectively.

Endoglin (CD105) expression differentiates between aseptic loosening and periprosthetic joint infection after total joint arthroplasty.

PubMed

Jansen, Philipp; Mumme, Torsten; Randau, Thomas; Gravius, Sascha; Hermanns-Sachweh, Benita

2014-01-01

The differentiation between aseptic loosening and periprosthetic joint infection (PJI) after total joint arthroplasty is essential for successful therapy. A better understanding of pathogenesis of aseptic loosening and PJI may help to prevent or treat these complications. Previous investigations revealed an increased vascularization in the periprosthetic membrane in cases of PJI via PET signals. Based on these findings our hypothesis was that PJI is associated with an increased neovascularization in the periprosthetic membrane. Tissue samples from periprosthetic membranes of the bone-implant interface were investigated histologically for inflammation, wear particles, vascularization and fibrosis. To identify vascular structures antibodies against CD 31, CD 34, factor VIII and CD 105 (endoglin) were applied for immunohistochemical investigations. According to a consensus classification of Morawietz the tissue samples were divided into four types: type I (wear particle induced type, n = 11), type II (infectious type, n = 7), type III (combined type, n = 7) and type IV (indeterminate type, n = 7). Patients with PJI (type II) showed a pronounced infiltration of neutrophil granulocytes in the periprosthetic membrane and an enhanced neovascularization indicated by positive immunoreaction with antibodies against CD 105 (endoglin). Tissue samples classified as type I, type III and type IV showed significantly less immune reaction for CD 105. In cases of aseptic loosening and PJI vascularization is found in different expression in periprosthetic membranes. However, in aseptic loosening, there is nearly no neovascularization with CD 105-positive immune reaction. Therefore, endoglin (CD 105) expression allows for differentiation between aseptic loosening and PJI.

Chondrogenesis in a hyaluronic acid scaffold: comparison between chondrocytes and MSC from bone marrow and adipose tissue.

PubMed

Jakobsen, Rune B; Shahdadfar, Aboulghassem; Reinholt, Finn P; Brinchmann, Jan E

2010-10-01

Treatment of focal lesions of the articular cartilage of the knee using chondrocytes in a hyaluronic acid (HA) scaffold is already being investigated in clinical trials. An alternative may be to use mesenchymal stem cells (MSC). We have compared articular chondrocytes with MSC from human bone marrow (BM) and adipose tissue (AT), all cultured in HA scaffolds, for their ability to express genes and synthesize proteins associated with chondrogenesis. The cells were expanded in monolayer cultures. After seeding into the scaffold, the chondrocytes were maintained in medium, while the two MSC populations were given a chondrogenic differentiation medium. Chondrogenesis was assessed by real-time RT-PCR for chondrocyte-associated genes, by immunohistochemistry and by ELISA for collagens in the supernatant. Redifferentiation of the dedifferentiated chondrocytes in the HA scaffold was shown by a modest increase in type II collagen mRNA (COL2A1) and reduction in COL1A1. BM-MSC expressed 600-fold higher levels of COL2A1 than chondrocytes after 3 weeks in the scaffold. The levels of aggrecan (AGC1) and COL1A1 were similar for chondrocyte and BM-MSC scaffold cultures, while COL10A1 was higher in the BM-MSC. AT-MSC expressed levels of COL2A1 and COL1A1 similar to chondrocytes, but less AGC1 and COL10A1. Surprisingly, little collagen II protein was observed in the scaffold. Instead, collagen II was found in the culture medium. Chondrogenesis in HA scaffolds was more efficient using BM-MSC than AT-MSC or chondrocytes. Some of the secreted collagen II escaped entrapment in the extracellular space and was detected in the culture medium.

Localized bone regeneration around dental implants using recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB in the canine.

PubMed

Thoma, Daniel S; Cha, Jae-Kook; Sapata, Vitor M; Jung, Ronald E; Hüsler, Juerg; Jung, Ui-Won

2017-11-01

To test whether or not one of two biological mediators (recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor (rhPDGF-BB)) is superior to the other and compared with control groups for bone regeneration around implants based on histomorphometrical outcome measures. Box-type defects (10 × 5 × 5 mm) were prepared on the buccal sides of the left and right edentulous ridge in ten mongrel dogs. Implants were placed at each site, the defects either received (i) bovine-derived particulated bone mineral (DBBM) mixed with rhBMP-2 and a collagen membrane (CM) (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB and CM (DBBM/PDGF), (iii) DBBM and CM (DBBM) and (iv) empty control (control). Animals were euthanized post-surgery at 8 weeks and 16 weeks. Histomorphometrical analyses were performed. The mean percentages of regenerated area within total defect area amounted to 56.95% for DBBM/BMP-2, 48.86% for DBBM/PDFG, 33.44% for DBBM and 1.59% for control at 8 weeks, and 26.79% for DBBM/BMP-2, 23.78% for DBBM/PDFG, 30.21% for DBBM and 5.07% for control at 16 weeks with no statistically significant differences between the groups (P > 0.05). The mean amount of regenerated bone was 26.97% for DBBM/BMP-2, 22.02% for DBBM/PDFG, 5.03% for DBBM and 1.25% for control at 8 weeks, and at 16 weeks, these values were lower in the two groups with biological mediators (DBBM/BMP-2 = 13.35%; DBBM/PDGF = 6.96%) and only slightly increased in group DBBM (10.68%) and the control group (4.95%) compared with 8 weeks. The first bone-to-implant contact values on the buccal side were minimal for DBBM/BMP-2 (0.57 mm) and maximal for control (3.72 mm) at 8 weeks. The use of biological mediators (rhBMP-2 and rhPDGF-BB) can increase the amount of bone regeneration at dehiscence-type defects compared with controls at 8 weeks, but not at 16 weeks due to enhanced hard tissue remodeling processes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CCN3 Protein Participates in Bone Regeneration as an Inhibitory Factor*

PubMed Central

Matsushita, Yuki; Sakamoto, Kei; Tamamura, Yoshihiro; Shibata, Yasuaki; Minamizato, Tokutaro; Kihara, Tasuku; Ito, Masako; Katsube, Ken-ichi; Hiraoka, Shuichi; Koseki, Haruhiko; Harada, Kiyoshi; Yamaguchi, Akira

2013-01-01

CCN3, a member of the CCN protein family, inhibits osteoblast differentiation in vitro. However, the role of CCN3 in bone regeneration has not been well elucidated. In this study, we investigated the role of CCN3 in bone regeneration. We identified the Ccn3 gene by microarray analysis as a highly expressed gene at the early phase of bone regeneration in a mouse bone regeneration model. We confirmed the up-regulation of Ccn3 at the early phase of bone regeneration by RT-PCR, Western blot, and immunofluorescence analyses. Ccn3 transgenic mice, in which Ccn3 expression was driven by 2.3-kb Col1a1 promoter, showed osteopenia compared with wild-type mice, but Ccn3 knock-out mice showed no skeletal changes compared with wild-type mice. We analyzed the bone regeneration process in Ccn3 transgenic mice and Ccn3 knock-out mice by microcomputed tomography and histological analyses. Bone regeneration in Ccn3 knock-out mice was accelerated compared with that in wild-type mice. The mRNA expression levels of osteoblast-related genes (Runx2, Sp7, Col1a1, Alpl, and Bglap) in Ccn3 knock-out mice were up-regulated earlier than those in wild-type mice, as demonstrated by RT-PCR. Bone regeneration in Ccn3 transgenic mice showed no significant changes compared with that in wild-type mice. Phosphorylation of Smad1/5 was highly up-regulated at bone regeneration sites in Ccn3 KO mice compared with wild-type mice. These results indicate that CCN3 is up-regulated in the early phase of bone regeneration and acts as a negative regulator for bone regeneration. This study may contribute to the development of new strategies for bone regeneration therapy. PMID:23653360

The Src-like adaptor protein regulates GM-CSFR signaling and monocytic dendritic cell maturation.

PubMed

Liontos, Larissa M; Dissanayake, Dilan; Ohashi, Pamela S; Weiss, Arthur; Dragone, Leonard L; McGlade, C Jane

2011-02-15

GM-CSF is an important cytokine involved in myeloid differentiation and inflammatory processes. Signaling through the GM-CSFR also plays a critical role in the generation of monocyte-derived dendritic cells (DC). In this article, we report that the Src-like adaptor protein (SLAP) functions as a negative regulator of the GM-CSFR. In bone marrow-derived DC (BM-DC) lacking SLAP and the closely related SLAP2, downregulation of GM-CSFRβ is impaired, leading to enhanced phosphorylation of Jak2 and prolonged activation of Akt and Erk1/2 in response to GM-CSF stimulation. Compared with wild-type bone marrow, SLAP/SLAP2(-/-) bone marrow gave rise to similar numbers of CD11c(+) and CD11b(+) DC, but SLAP/SLAP2(-/-) BM-DC failed to acquire high levels of MHC class II, CD80, and CD86, indicating an impairment in maturation. Furthermore, MHC class II expression in SLAP/SLAP2(-/-) BM-DC was rescued by decreasing GM-CSF concentration, suggesting that enhanced GM-CSF signaling mediates the block in maturation. In addition, SLAP/SLAP2(-/-) BM-DC produced less IL-12 and TNF-α in response to LPS compared with controls and failed to stimulate T cells in an MLR. Ag-specific T cell activation assays showed that SLAP/SLAP2(-/-) BM-DC were less robust at inducing IFN-γ secretion by DO11.10 T cells. These results indicated that SLAP-mediated GM-CSFR regulation is important for the generation of functionally mature monocytic DC.

Correlating the nanoscale mechanical and chemical properties of knockout mice bones

NASA Astrophysics Data System (ADS)

Kavukcuoglu, Nadire Beril

Bone is a mineral-organic composite where the organic matrix is mainly type I collagen plus small amounts of non-collagenous proteins including osteopontin (OPN), osteocalcin (OC) and fibrillin 2 (Fbn2). Mature bone undergoes remodeling continually so new bone is formed and old bone resorbed. Uncoupling between the bone resorption and bone formation causes an overall loss of bone mass and leads to diseases like osteoporosis and osteopenia. These are characterized by structural deterioration of the bone tissue and an increased risk of fracture. The non-collagenous bone proteins are known to have a role in regulating bone turnover and to affect the structural integrity of bone. OPN and OC play a key role in bone resorption and formation, while absence of Fbn-2 causes a connective tissue disorder (congenital contractural arachnodactyly) and has been associated with decreased bone mass. In this thesis nanoindentation and Raman-microspectroscopy techniques were used to investigate and correlate the mechanical and chemical properties of cortical femoral bones from OPN deficient (OPN-/-), OC deficient (OC-/-) and Fbn-2 deficient (Fbn2-/-) mice and their age, sex and background matched wild-type controls (OPN+/+, OC+/+ and Fbn2+/+). For OPN the hardness (H) and elastic modulus (E) of under 12 week OPN-/- bones were significantly lower than for OPN+/+ bones, but Raman showed no significant difference. Mechanical properties of bones from mice older than 12 weeks were not significantly different with genotype. However, mineralization and crystallinity from >50 week OPN-/- bones were significantly higher than for OPN+/+ bones. Mechanical properties of OPN-/- bones showed no variation with age, but mineralization, crystallinity and type-B carbonate substitution increased for both genotypes. For OC-/- intra-bone analyses showed that the hardness and crystallinity of the bones were significantly higher, especially in the mid-cortical sections, compared to OC+/+ bones. Fbn2-/- bones had significantly lower hardness and elastic modulus compared to Fbn2+/+ bones, but the crystallinity was higher. Type-B carbonate substitution decreased significantly in OC-/- and Fbn2-/- bones compared to their wild-type controls. The thesis has provided new insight into how non-collagenous proteins affect the nanomechanics and chemistry of bone tissue. This information will assist in the development of new treatments for osteopenia/osteoporosis.

[Alterations of bone metabolism in children and adolescents with diabetes mellitus type 1].

PubMed

Pater, Agnieszka; Odrowąż-Sypniewska, Grażyna

2011-01-01

Diabetes mellitus type 1 is one of the most common chronic diseases in children and adolescents. The incidence of diabetes mellitus type 1 is increasing rapidly worldwide. Recently, the largest rate of increase is observed in children aged 0-4 years. Chronic hyperglycemia leads to microvascular and macrovascular complications including retinopathy, nephropathy, neuropathy and cardiomyopathy. Pathological changes occur in the bone structure. The lack of diagnosis and treatment of alterations of the bone tIssue metabolism may lead to osteoporosis, which is characterized by much reduced bone mineral density and changes in the microarchitecture of the bone tIssue, which in consequence results in increased susceptibility to fractures. Diabetes mellitus type 1 most often starts before achieving peak bone mass, which constitutes a point of reference for predicting risk of fractures in a later period of life. Mechanisms responsible for loss of the bone tIssue in diabetes of type 1 still remain unexplained. Many research findings indicate the anabolic role of insulin and insulin-like growth factors, mainly IGF-1. The aim of this manuscript is to review recent papers about alterations of bone metabolism in children and adolescents with diabetes mellitus type 1.

Bone Sialoproteins and Breast Cancer Detection

DTIC Science & Technology

2004-07-01

used to follow proteolytic activity on more natural macromolecular substrates. These substrates are so highly substituted with fluorescein moieties that...uninformative for breast cancer, but does correlate with bone mineral density, parathyroid hormone and phosphorus . (Summary of Appendix II). Normal MEPE...calcium, phosphorus , vitamin D, as well as novel phosphatonin(s), and the bone and kidney organs. Candidate phosphaturic factors include MEPE; PHEX, a

[Assessment of the hearing results in tympanoplasties with the use of palisade-technique].

PubMed

Wielgosz, Romuald; Mroczkowski, Edward

2006-01-01

The cartilage has been successfuly used in reconstructive ear surgery for more than one hundred years. Histologic study of autografts cartilage (tragal or conchal) showed good long-term preservation of cartilage cells. The aim of this paper is to assess the hearing results in tympanoplasties with the use of cartilage palisade technique. The retrospective analysis concerned 108 operated clinical cases. The cartilage palisade technique was performed in 28 tympanoplasties type I, 47 tympanoplasties type II, 21 tympanoplasties type III with columella and in 2 tympanoplasties type IV. Clinical assessment included otoscopy, test for eustachian tube ventilation, test with tuning fork, audiometry on a range 0,5, 1, 2 kHz and subjective evaluation based on questionaire. The Air Bone Gap (ABG) was noted as follows: < 10 dB among 67,8% of patients and 11-20 dB among 21,4% of patients in tympanoplasty type I. In tympanoplasty type II the ABG was responsively: < 10 dB - 80% patients, 11-20 dB - 10% patients. In the type III of tympanoplasty 40,4% of patients showed ABG < 10 dB and 42,5% of patients 11-20 dB. In the type III with columella we noted 15% patients with ABG < 10 dB and 65% of them with ABG 11-20 dB. The cartilage is a good autograft for reconstruction of the tympanic membrane, middle ear and the auditory wall because of stability and lack of secondary perforations. Long-term results in hearing are also satisfactory.

[The spectrum of histomorphological findings related to joint endoprosthetics].

PubMed

Morawietz, L; Krenn, V

2014-11-01

Approximately 230,000 total hip and 170,000 knee joint endoprostheses are implanted in Germany annually of which approximately 10% (i.e. 40,000 interventions per year) are cases of revision surgery. These interventions involve removal of a previously implanted prosthesis which has resulted in complaints and replacement with a new prosthesis. There are manifold reasons for revision surgery, the most common indication being so-called endoprosthesis loosening, which is subdivided into septic and aseptic loosening. Histomorphological studies revealed that periprosthetic tissue from endoprosthesis loosening can be classified into four types (I) wear-particle induced type, (II) infectious type, (III) combined type and (IV) fibrous type. Types I and IV represent aseptic loosening and types II and III septic loosening. Recently, the topic of implant allergy has emerged. The detection of cellular, mostly perivascular lymphocytic infiltrates is discussed as being a sign of an allergic tissue reaction. It has most frequently been observed in type I periprosthetic membranes with a dense load of metal wear, which occurs with metal-on-metal bearings. Apart from endoprosthesis loosening, arthrofibrosis is another complication of joint endoprosthetics and can cause pain and impaired function. Histopathologically, arthrofibrosis can be evaluated by a three-tiered grading system. Furthermore, bone pathologies, such as ossification, osteopenia or osteomyelitis can occur as complications of joint endoprosthetics. This review gives an overview of the whole spectrum of pathological findings in joint endoprosthetics and offers a comprehensive and standardized classification system for routine histopathological diagnostics.

Bone metastases from breast cancer at the time or radical mastectomy as detected by bone scan. Eight-year follow-up.

PubMed

Sklaroff, R B; Sklaroff, D M

1976-07-01

Sixty-four women with Stage II breast cancer who had Sr85 bone scans at the time of radical mastectomy were followed for 8 years in a prospective study. Those women with positive scans had a slight, but statistically significant, increased incidence of metastic disease, particularly for metastases to bone.However, 40% of those women with positive bone scans and negative roentgenograms survived 8 years without evidence of any metastatic disease. Therefore, it has not been shown at this time that bone scans should be obtained in order to exclude bone metastasis before regional therapy for breast cancer is instituted. Also, a significant percentage of women with negative bone scans developed both bone and soft tissue metastases. As many as 30% of asymptomatic women with a history of breast cancer and positive bone scans and negative bone roentgenograms may still harbor disease in bone after 8 years.

The use of weightbearing radiographs to assess the stability of supination-external rotation fractures of the ankle.

PubMed

Weber, Martin; Burmeister, Helge; Flueckiger, Gerhard; Krause, Fabian G

2010-05-01

Isolated lateral malleolar fractures usually result from a supination-external rotation (SER) injury and may include a deltoid ligament rupture. The necessity of operative treatment is based on the recognition of a relevant medial soft-tissue disruption. Currently used tests to assess ankle stability include manual stress radiographs and gravity stress radiographs, but seem to overestimate the need for fracture fixation. We investigated the use of weightbearing radiographs to distinguish stable and unstable isolated lateral malleolar fractures induced by the SER mechanism in 57 patients. Patients with stable fractures (SER type II according to the Lauge-Hansen classification) were treated non-operatively with varying external support. Forty-seven patients were evaluated by questionnaire and AOFAS ankle-hindfoot score. Follow-up was 18-120 months (mean 62). Fifty-one of fifty-seven (90%) patients were found to have stable fractures (SER type II) and were treated nonoperatively. The AOFAS score was 96.1 points on average (range 85-100) at latest follow-up. Four patients reported minor complaints. A "moderate" correlation of risk factors (i.e. smoking) to delayed bone healing was found while the correlation of varying external support (i.e. bandage, cast) to the AOFAS score and delayed bone healing was "poor". The use of weightbearing radiographs is an easy, pain-free, safe and reliable method to exclude the need for operative treatment, with excellent clinical outcome in the majority of the patients seen at latest follow-up. The delay of 3-10 days until the decision about surgical treatment is well accepted by the patients.

A Comparison of More and Less Aggressive Bone Debridement Protocols for the Treatment of Open Supracondylar Femur Fractures

PubMed Central

Ricci, William M.; Collinge, Cory; Streubel, Philipp N.; McAndrew, Christopher M.; Gardner, Michael J.

2014-01-01

Objectives This study compared results of aggressive and nonaggressive debridement protocols for the treatment of high energy open supracondylar femur fractures after the primary procedure, with respect to the requirement for secondary bone grafting procedures, and deep infection. Design Retrospective review Setting Level I and Level II Trauma Centers Patients/Participants Twenty-nine consecutive patients with high grade open (Gustilo Types II and III) supracondylar femur fractures (OTA/AO 33A and C) treated with debridement and locked plating. Intervention Surgeons at two different Level I trauma centers had different debridement protocols for open supracondylar femur fractures. One center used a More Aggressive (MA)protocol in their patients (n=17) that included removal of all devitalized bone and placement of antibiotic cement spacers to fill large segmental defects. The other center used a Less Aggressive (LA) protocol in their patients (n=12) that included debridement of grossly contaminated bone with retention of other bone fragments and no use of antibiotic cement spacers. All other aspects of the treatment protocol at the two centers were similar: definitive fixation with locked plates in all cases; IV antibiotics were used until definitive wound closure; and weight bearing was advanced upon clinical and radiographic evidence of fracture healing. Main Outcome Measurements Healing after the primary procedure, requirement for secondary bone grafting procedures, and the presence of deep infection. Results Demographics were similar between included patients at each center with regard to: age; gender; rate of open fractures; open fracture classification; mechanism; and smoking (p>.05). Patients at the MA center were more often diabetic (p<.05).Cement spacers to fill segmental defects were used more often after MA debridement (35% vs 0%, p<0.006) and more patients had a plan for staged bone grafting after MA debridement (71% vs 8%, p<0.006). Healing after the index fixation procedure occurred more often after LA debridement (92% vs 35%, p<0.003). There was no difference in infection rate between the two protocols: 25% with the LA protocol; and 18% with the MA protocol, (p=0.63). All patients in both groups eventually healed and were without evidence of infection at an average of 1.8 years of follow-up. Conclusion The degree to which bone should be debrided after a high energy, high grade, open supracondylar femur fracture is a matter of surgeon judgment and falls along a continuous spectrum. Based on the results of the current study, the theoretic tradeoff between infection risk and osseous healing potential, seems to favor a less aggressive approach towards bone debridement in the initial treatment. PMID:23760177

A comparison of more and less aggressive bone debridement protocols for the treatment of open supracondylar femur fractures.

PubMed

Ricci, William M; Collinge, Cory; Streubel, Philipp N; McAndrew, Christopher M; Gardner, Michael J

2013-12-01

This study compared results of aggressive and nonaggressive debridement protocols for the treatment of high-energy, open supracondylar femur fractures after the primary procedure, with respect to the requirement for secondary bone grafting procedures, and deep infection. Retrospective review. Level I and level II trauma centers. Twenty-nine consecutive patients with high-grade, open (Gustilo types II and III) supracondylar femur fractures (OTA/AO 33A and C) treated with debridement and locked plating. Surgeons at 2 different level I trauma centers had different debridement protocols for open supracondylar femur fractures. One center used a more aggressive (MA) protocol in their patients (n = 17) that included removal of all devitalized bone and placement of antibiotic cement spacers to fill large segmental defects. The other center used a less aggressive (LA) protocol in their patients (n = 12) that included debridement of grossly contaminated bone with retention of other bone fragments and no use of antibiotic cement spacers. All other aspects of the treatment protocol at the 2 centers were similar: definitive fixation with locked plates in all cases, IV antibiotics were used until definitive wound closure, and weight bearing was advanced upon clinical and radiographic evidence of fracture healing. Healing after the primary procedure, requirement for secondary bone grafting procedures, and the presence of deep infection. Demographics were similar between included patients at each center with regard to age, gender, rate of open fractures, open fracture classification, mechanism, and smoking (P > 0.05). Patients at the MA center were more often diabetic (P < 0.05). Cement spacers to fill segmental defects were used more often after MA debridement (35% vs. 0%, P < 0.006), and more patients had a plan for staged bone grafting after MA debridement (71% vs. 8%, P < 0.006). Healing after the index fixation procedure occurred more often after LA debridement (92% vs. 35%, P < 0.003). There was no difference in infection rate between the 2 protocols: 25% with the LA protocol and 18% with the MA protocol (P = 0.63). All patients in both groups eventually healed and were without evidence of infection at an average of 1.8 years of follow-up. The degree to which bone should be debrided after a high-energy, high-grade, open supracondylar femur fracture is a matter of surgeon judgment and falls along a continuous spectrum. Based on the results of the current study, the theoretic trade-off between infection risk and osseous healing potential seems to favor an LA approach toward bone debridement in the initial treatment. Therapeutic level III.

[Bone turnover in children and adolescents with diabetes mellitus type 1].

PubMed

Pater, Agnieszka; Odrowąż-Sypniewska, Grażyna

2013-01-01

Biochemical bone turnover markers are fragments of protein structural elements of the bone created during the synthesis or degradation and enzymes specific for bone cells, released into the circulation during the metabolic activity of osteoblasts and osteoclasts. Bone turnover markers are used as indicators to evaluate the activity of modeling and remodeling processes. They are the result of the activity of all remodeling processes taking place at the moment in the whole skeleton. The assay allows quick assessment of the rate of bone formation and resorption processes. Among many complications in children with type 1 diabetes increased bone turnover leading to a reduction in bone mass may increase the risk of osteopenia or osteoporosis in adulthood. The aim of this manuscript is to review recent papers about bone turnover in children and adolescents with diabetes mellitus type 1.

The use of a cartilage decellularized matrix scaffold for the repair of osteochondral defects: the importance of long-term studies in a large animal model.

PubMed

Vindas Bolaños, R A; Cokelaere, S M; Estrada McDermott, J M; Benders, K E M; Gbureck, U; Plomp, S G M; Weinans, H; Groll, J; van Weeren, P R; Malda, J

2017-03-01

To investigate the effect of decellularized cartilage-derived matrix (CDM) scaffolds, by itself and as a composite scaffold with a calcium phosphate (CaP) base, for the repair of osteochondral defects. It was hypothesized that the chondral defects would heal with fibrocartilaginous tissue and that the composite scaffold would result in better bone formation. After an 8-week pilot experiment in a single horse, scaffolds were implanted in eight healthy horses in osteochondral defects on the medial trochlear ridge of the femur. In one joint a composite CDM-CaP scaffold was implanted (+P), in the contralateral joint a CDM only (-P) scaffold. After euthanasia at 6 months, tissues were analysed by histology, immunohistochemistry, micro-CT, biochemistry and biomechanical evaluation. The 8-week pilot showed encouraging formation of bone and cartilage, but incomplete defect filling. At 6 months, micro-CT and histology showed much more limited filling of the defect, but the CaP component of the +P scaffolds was well integrated with the surrounding bone. The repair tissue was fibrotic with high collagen type I and low type II content and with no differences between the groups. There were also no biochemical differences between the groups and repair tissue was much less stiff than normal tissue (P < 0.0001). The implants failed to produce reasonable repair tissue in this osteochondral defect model, although the CaP base in the -P group integrated well with the recipient bone. The study stresses the importance of long-term in vivo studies to assess the efficacy of cartilage repair techniques. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effects of radial compression on a novel simulated intervertebral disc-like assembly using bone marrow-derived mesenchymal stem cell cell-sheets for annulus fibrosus regeneration.

PubMed

See, Eugene Yong-Shun; Toh, Siew Lok; Goh, James Cho-Hong

2011-10-01

The aim of this study was to develop a tissue engineering approach in regenerating the annulus fibrosus (AF) as part of an overall strategy to produce a tissue-engineered intervertebral disc (IVD) replacement. To determine whether a rehabilitative simulation regime on bone marrow–derived mesenchymal stem cell cell-sheet is able to aid the regeneration of the AF. No previous study has used bone marrow–derived mesenchymal stem cell cell-sheets simulated by a rehabilitative regime to regenerate the AF. The approach was to use bone marrow–derived stem cells to form cell-sheets and incorporating them onto silk scaffolds to simulate the native lamellae of the AF. The in vitro experimental model used to study the efficacy of such a system was made up of the tissue engineering AF construct wrapped around a silicone disc to form a simulated IVD-like assembly. The assembly was cultured within a custom-designed bioreactor that provided a compressive mechanical stimulation onto the silicone disc. The silicone nucleus pulposus would bulge radially and compress the simulated AF to mimic the physiological conditions. The simulated IVD-like assembly was compressed using a rehabilitative regime that lasted for 4 weeks at 0.25 Hz, for 15 minutes each day. With the rehabilitative regime, the cell-sheets remained viable but showed a decrease in cell numbers and viability. Gene expression analysis showed significant upregulation of IVD-related genes and there was an increased ratio of collagen type II to collagen type I found within the extracellular matrix. The results suggested that a rehabilitative regime caused extensive remodeling to take place within the simulated IVD-like assembly, producing extracellular matrix similar to that found in the inner AF.

Behavior of bone cells in contact with magnesium implant material.

PubMed

Burmester, Anna; Willumeit-Römer, Regine; Feyerabend, Frank

2017-01-01

Magnesium-based implants exhibit several advantages, such as biodegradability and possible osteoinductive properties. Whether the degradation may induce cell type-specific changes in metabolism still remains unclear. To examine the osteoinductivity mechanisms, the reaction of bone-derived cells (MG63, U2OS, SaoS2, and primary human osteoblasts (OB)) to magnesium (Mg) was determined. Mg-based extracts were used to mimic more realistic Mg degradation conditions. Moreover, the influence of cells having direct contact with the degrading Mg metal was investigated. In exposure to extracts and in direct contact, the cells decreased pH and osmolality due to metabolic activity. Proliferating cells showed no significant reaction to extracts, whereas differentiating cells were negatively influenced. In contrast to extract exposure, where cell size increased, in direct contact to magnesium, cell size was stable or even decreased. The amount of focal adhesions decreased over time on all materials. Genes involved in bone formation were significantly upregulated, especially for primary human osteoblasts. Some osteoinductive indicators were observed for OB: (i) an increased cell count after extract addition indicated a higher proliferation potential; (ii) increased cell sizes after extract supplementation in combination with augmented adhesion behavior of these cells suggest an early switch to differentiation; and (iii) bone-inducing gene expression patterns were determined for all analyzed conditions. The results from the cell lines were inhomogeneous and showed no specific stimulus of Mg. The comparison of the different cell types showed that primary cells of the investigated tissue should be used as an in vitro model if Mg is analyzed. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 165-179, 2017. © 2015 Wiley Periodicals, Inc.

Concave Pit-Containing Scaffold Surfaces Improve Stem Cell-Derived Osteoblast Performance and Lead to Significant Bone Tissue Formation

PubMed Central

Cusella-De Angelis, Maria Gabriella; Laino, Gregorio; Piattelli, Adriano; Pacifici, Maurizio; De Rosa, Alfredo; Papaccio, Gianpaolo

2007-01-01

Background Scaffold surface features are thought to be important regulators of stem cell performance and endurance in tissue engineering applications, but details about these fundamental aspects of stem cell biology remain largely unclear. Methodology and Findings In the present study, smooth clinical-grade lactide-coglyolic acid 85:15 (PLGA) scaffolds were carved as membranes and treated with NMP (N-metil-pyrrolidone) to create controlled subtractive pits or microcavities. Scanning electron and confocal microscopy revealed that the NMP-treated membranes contained: (i) large microcavities of 80–120 µm in diameter and 40–100 µm in depth, which we termed primary; and (ii) smaller microcavities of 10–20 µm in diameter and 3–10 µm in depth located within the primary cavities, which we termed secondary. We asked whether a microcavity-rich scaffold had distinct bone-forming capabilities compared to a smooth one. To do so, mesenchymal stem cells derived from human dental pulp were seeded onto the two types of scaffold and monitored over time for cytoarchitectural characteristics, differentiation status and production of important factors, including bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF). We found that the microcavity-rich scaffold enhanced cell adhesion: the cells created intimate contact with secondary microcavities and were polarized. These cytological responses were not seen with the smooth-surface scaffold. Moreover, cells on the microcavity-rich scaffold released larger amounts of BMP-2 and VEGF into the culture medium and expressed higher alkaline phosphatase activity. When this type of scaffold was transplanted into rats, superior bone formation was elicited compared to cells seeded on the smooth scaffold. Conclusion In conclusion, surface microcavities appear to support a more vigorous osteogenic response of stem cells and should be used in the design of therapeutic substrates to improve bone repair and bioengineering applications in the future. PMID:17551577

Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts.

PubMed

Komatsu, Yuko; Ibi, Miho; Chosa, Naoyuki; Kyakumoto, Seiko; Kamo, Masaharu; Shibata, Toshiyuki; Sugiyama, Yoshiki; Ishisaki, Akira

2016-07-01

Bisphosphonates (BPs) are analogues of pyrophosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of the jaw (BRONJ) in cancer patients. The molecular pathological mechanisms responsible for the development of BRONJ, including necrotic bone exposure after tooth extraction, remain to be elucidated. In this study, we examined the effects of ZA on the transforming growth factor-β (TGF‑β)-induced myofibroblast (MF) differentiation of human gingival fibroblasts (hGFs) and the migratory activity of hGFs, which are important for wound closure by fibrous tissue formation. The ZA maximum concentration in serum (Cmax) was found to be approximately 1.47 µM, which clinically, is found after the intravenous administration of 4 mg ZA, and ZA at this dose is considered appropriate for the treatment of cancer bone metastasis or bone diseases, such as Erdheim-Chester disease. At Cmax, ZA significantly suppressed i) the TGF‑β-induced promotion of cell viability, ii) the TGF‑β-induced expression of MF markers such as α-smooth muscle actin (α-SMA) and type I collagen, iii) the TGF‑β-induced migratory activity of hGFs and iv) the expression level of TGF‑β type I receptor on the surfaces of hGFs, as well as the TGF‑β-induced phosphorylation of Smad2/3. Thus, ZA suppresses TGF‑β-induced fibrous tissue formation by hGFs, possibly through the inhibition of Smad‑dependent signal transduction. Our findings partly elucidate the molecular mechanisms underlying BRONJ and may prove to be beneficial to the identification of drug targets for the treatment of this symptom at the molecular level.

Small-Diameter Awls Improve Articular Cartilage Repair After Microfracture Treatment in a Translational Animal Model.

PubMed

Orth, Patrick; Duffner, Julia; Zurakowski, David; Cucchiarini, Magali; Madry, Henning

2016-01-01

Microfracture is the most commonly applied arthroscopic marrow stimulation procedure. Articular cartilage repair is improved when the subchondral bone is perforated by small-diameter microfracture awls compared with larger awls. Controlled laboratory study. Standardized rectangular (4 × 8 mm) full-thickness chondral defects (N = 24) were created in the medial femoral condyle of 16 adult sheep and debrided down to the subchondral bone plate. Three treatment groups (n = 8 defects each) were tested: 6 microfracture perforations using small-diameter awls (1.0 mm; group 1), large-diameter awls (1.2 mm; group 2), or without perforations (debridement control; group 3). Osteochondral repair was assessed at 6 months in vivo using established macroscopic, histological, immunohistochemical, biochemical, and micro-computed tomography analyses. Compared with control defects, histological cartilage repair was always improved after both microfracture techniques (P < .023). Application of 1.0-mm microfracture awls led to a significantly improved histological overall repair tissue quality (7.02 ± 0.70 vs 9.03 ± 0.69; P = .008) and surface grading (1.05 ± 0.28 vs 2.10 ± 0.19; P = .001) compared with larger awls. The small-diameter awl decreased relative bone volume of the subarticular spongiosa (bone volume/tissue volume ratio: 23.81% ± 3.37% vs 30.58% ± 2.46%; P = .011). Subchondral bone cysts and intralesional osteophytes were frequently observed after either microfracture treatment. Macroscopic grading, DNA, proteoglycan, and type I and type II collagen contents as well as degenerative changes within the adjacent cartilage remained unaffected by the awl diameter. Small-diameter microfracture awls improve articular cartilage repair in the translational sheep model more effectively than do larger awls. These data support the use of small microfracture instruments for the surgical treatment of cartilage defects and warrant prolonged clinical investigations. © 2015 The Author(s).

Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.

PubMed

Windahl, Sara H; Andersson, Niklas; Börjesson, Anna E; Swanson, Charlotte; Svensson, Johan; Movérare-Skrtic, Sofia; Sjögren, Klara; Shao, Ruijin; Lagerquist, Marie K; Ohlsson, Claes

2011-01-01

Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05) and cortical bone mineral content (-15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.

Reduced Bone Mass and Muscle Strength in Male 5α-Reductase Type 1 Inactivated Mice

PubMed Central

Windahl, Sara H.; Andersson, Niklas; Börjesson, Anna E.; Swanson, Charlotte; Svensson, Johan; Movérare-Skrtic, Sofia; Sjögren, Klara; Shao, Ruijin; Lagerquist, Marie K.; Ohlsson, Claes

2011-01-01

Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1−/− mice. Four-month-old male Srd5a1 −/− mice had reduced trabecular bone mineral density (−36%, p<0.05) and cortical bone mineral content (−15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1 −/− mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1 −/− mice. Male Srd5a1 −/− mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1 −/− mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1 −/− mice, is an indirect effect mediated by elevated circulating androgen levels. PMID:21731732

A genotoxic analysis of the hematopoietic system after mobile phone type radiation exposure in rats.

PubMed

Kumar, Gaurav; McIntosh, Robert L; Anderson, Vitas; McKenzie, Ray J; Wood, Andrew W

2015-08-01

In our earlier study we reported that 900 MHz continuous wave (CW) radiofrequency radiation (RFR) exposure (2 W/kg specific absorption rate [SAR]) had no significant effect on the hematopoietic system of rats. In this paper we extend the scope of the previous study by testing for possible effects at: (i) different SAR levels; (ii) both 900 and 1800 MHz, and; (iii) both CW and pulse modulated (PM) RFR. Excised long bones from rats were placed in medium and RFR exposed in (i) a Transverse Electromagnetic (TEM) cell or (ii) a waveguide. Finite-difference time-domain (FDTD) numerical analyses were used to estimate forward power needed to produce nominal SAR levels of 2/10 and 2.5/12.4 W/kg in the bone marrow. After exposure, the lymphoblasts were extracted and assayed for proliferation rate, and genotoxicity. Our data did not indicate any significant change in these end points for any combination of CW/PM exposure at 900/1800 MHz at SAR levels of nominally 2/10 W/kg or 2.5/12.4 W/kg. No significant changes were observed in the hematopoietic system of rats after the exposure of CW/PM wave 900 MHz/1800 MHz RF radiations at different SAR values.

Joint Inflammation and Early Degeneration Induced by High-Force Reaching Are Attenuated by Ibuprofen in an Animal Model of Work-Related Musculoskeletal Disorder

PubMed Central

Driban, Jeffrey B.; Barr, Ann E.; Amin, Mamta; Sitler, Michael R.; Barbe, Mary F.

2011-01-01

We used our voluntary rat model of reaching and grasping to study the effect of performing a high-repetition and high-force (HRHF) task for 12 weeks on wrist joints. We also studied the effectiveness of ibuprofen, administered in the last 8 weeks, in attenuating HRHF-induced changes in these joints. With HRHF task performance, ED1+ and COX2+ cells were present in subchondral radius, carpal bones and synovium; IL-1alpha and TNF-alpha increased in distal radius/ulna/carpal bones; chondrocytes stained with Terminal deoxynucleotidyl Transferase- (TDT-) mediated dUTP-biotin nick end-labeling (TUNEL) increased in wrist articular cartilages; superficial structural changes (e.g., pannus) and reduced proteoglycan staining were observed in wrist articular cartilages. These changes were not present in normal controls or ibuprofen treated rats, although IL-1alpha was increased in reach limbs of trained controls. HRHF-induced increases in serum C1,2C (a biomarker of collagen I and II degradation), and the ratio of collagen degradation to synthesis (C1,2C/CPII; the latter a biomarker of collage type II synthesis) were also attenuated by ibuprofen. Thus, ibuprofen treatment was effective in attenuating HRHF-induced inflammation and early articular cartilage degeneration. PMID:21403884

Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones.

PubMed

Baris, Hagit N; Weisz Hubshman, Monika; Bar-Sever, Zvi; Kornreich, Liora; Shkalim Zemer, Vered; Cohen, Ian J

2016-09-01

Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas. Copyright © 2015 Elsevier Inc. All rights reserved.

Use of various diagnostic methods in a patient with Gaucher disease type I.

PubMed

Farahati, J; Trenn, G; John-Mikolajewski, V; Zander, C; Pastores, G M; Sciuk, J; Reiners, C

1996-08-01

A series of plain radiographs, bone scans, bone marrow scans, and MRIs is reported in a patient with Gaucher disease type I, in whom two episodes of acute bone crisis developed during a 6-year period of follow-up. Acute bone crisis and global indolent bone marrow displacement could both be assessed by bone marrow scintigraphy, whereas MRI could better clarify the corti-comedullary alteration after bone infarction. Thus, MRI and bone marrow scintigraphy could be used as complementary imaging methods in the management of patients with Gaucher disease.

As solid as a rock-comparison of CE- and MPS-based analyses of the petrosal bone as a source of DNA for forensic identification of challenging cranial bones.

PubMed

Kulstein, Galina; Hadrys, Thorsten; Wiegand, Peter

2018-01-01

Short tandem repeat (STR) typing from skeletal remains can be a difficult task. Dependent on the environmental conditions of the provenance of the bones, DNA can be degraded and STR typing inhibited. Generally, dense and compact bones are known to preserve DNA better. Several studies already proved that femora and teeth have high DNA typing success rates. Unfortunately, these elements are not present in all cases involving skeletal remains. Processing partial or singular skeletal elements, it is favorable to select bone areas where DNA preservation is comparably higher. Especially, cranial bones are often accidentally discovered during criminal investigations. The cranial bone is composed of multiple parts. In this examination, we evaluated the potential of the petrous bone for human identification of skeletal remains in forensic case work. Material from different sections of eight unknown cranial bones and-where available-additionally other skeletal elements, collected at the DNA department of the Institute of Legal Medicine in Ulm, Germany, from 2010 to 2017, were processed with an optimized DNA extraction and STR typing strategy. The results highlight that STR typing from the petrous bones leads to reportable profiles in all individuals, even in cases where the analysis of the parietal bone failed. Moreover, the comparison of capillary electrophorese (CE) typing to massively parallel sequencing (MPS) analysis shows that MPS has the potential to analyze degraded human remains and is even capable to provide additional information about phenotype and ancestry of unknown individuals.

In vitro stabilization of a low-tin bone-imaging agent (99mTc-Sn-HEDP) by ascorbic acid.

PubMed

Tofe, A J; Francis, M D

1976-09-01

The presence of oxidants in the 99mTc-pertechnetate and of oxygen in diagnostic kits containing low concentrations of Sn(II) has a detrimental effect upon in vitro and in vivo stability. Maintaining a nitrogen atmosphere or increasing the Sn(II) concentration inhibits the formation of 99mTcO4-. However, the latter remedy is likely to cause uptake in the reticuloendothelial system and has been associated with false positive or negative brain scans. We used ascorbic acid (an antioxidant) to ensure the in vitro stability with the low-Sn(II) bone agent disodium etidronate. In vitro stability studies by instant thin-layer chromatography, using high-acitivity generators and "instant pertechnetate," yielded less than 2% free pertechnetate at 24 hr after preparation. Distribution studies in guinea pigs show neither altered distribution of the bone agent nor abnormal distribution of ascorbic acid, suggesting its sole function as a noncomplexing stabilizer.

Discovery of Novel Drugs To Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin Pathway in Fracture Repair and Pseudarthrosis

DTIC Science & Technology

2014-06-01

Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin Pathway in Fracture Repair and Pseudarthrosis PRINCIPAL INVESTIGATOR...Award Number: W81XWH-13-1-0113 TITLE: Discovery of Novel Drugs To Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta-Catenin...31 May 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Discovery of Novel Drugs To Improve Bone Health in Neurofibromatosis Type 1: The Wnt/Beta

Strain gauges used in the mechanical testing of bones. Part II: "In vitro" and "in vivo" technique.

PubMed

Cordey, J; Gautier, E

1999-01-01

How to choose and prepare the strain gauges for bonding on bones "in vitro" and "in vivo"? This communication aims to elucidate technical details and some applications: direct assessment of the axial load, the bending moment, and the torque applied to long bones by the physiological loads. As a typical example of application, we will show the assessment of stress protection due to plates on the bones in the sheep tibia.

Effects of laser photherapy on bone defects grafted with mineral trioxide aggregate, bone morphogenetic proteins, and guided bone regeneration: a Raman spectroscopic study.

PubMed

Pinheiro, Antonio L B; Aciole, Gilberth T S; Cangussú, Maria Cristina T; Pacheco, Marcos T T; Silveira, Landulfo

2010-12-15

We have used Raman analysis to assess bone healing on different models. Benefits on the isolated or combined use of mineral trioxide aggregate, bone morphogenetic proteins, guided bone regeneration and laser on bone repair have been reported, but not their combination. We studied peaks of hydroxyapatite and CH groups on defects grafted with MTA, treated or not with laser, BMPs, and GBR. Ninety rats were divided in 10 groups each, subdivided into three subgroups. Laser (λ850 nm) was applied at every other day for 2 weeks. Raman readings were taken at the surface of the defect. Statistical analysis (CHA) showed significant differences between all groups (p = 0.001) and between Group II and all other (p < 0.001), but not with Group X (p = 0.09). At day 21 differences were seen between all groups (p = 0.031) and between Groups VIII and X when compared with Groups VI (p = 0.03), V (p < 0.001), IV (p < 0.001), and IX (p = 0.04). At the end of the experimental period no significant differences were seen. On regards CH, significant differences were seen at the 15(th) day (p = 0.002) and between Group II and all other groups (p < 0.0001) but not with control. Advanced maturation on irradiated bone is because of increased secretion of calcium hydroxyapatite (CHA) that is indicative of greater calcification and resistance of the bone. We conclude that the association of the MTA with laser phototherapy (LPT) and/or not with GBR resulted in a better bone repair. The use of the MTA associated to IR LPT resulted in a more advanced and quality bone repair. Copyright © 2010 Wiley Periodicals, Inc.

Cortical bone thickening in Type A posterior atlas arch defects: experimental report.

PubMed

Sanchis-Gimeno, Juan A; Llido, Susanna; Guede, David; Martinez-Soriano, Francisco; Ramon Caeiro, Jose; Blanco-Perez, Esther

2017-03-01

To date, no information about the cortical bone microstructural properties in atlas vertebrae with posterior arch defects has been reported. To test if there is an increased cortical bone thickening in atlases with Type A posterior atlas arch defects in an experimental model. Micro-computed tomography (CT) study on cadaveric atlas vertebrae. We analyzed the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry vertebrae with a Type A atlas arch defect and normal control vertebrae. The micro-CT study revealed significant differences in cortical bone thickness (p=.005), cortical volume (p=.003), and medullary volume (p=.009) values between the normal and the Type A vertebrae. Type A congenital atlas arch defects present a cortical bone thickening that may play a protective role against atlas fractures. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog.

PubMed

Kawamoto, Kohei; Miyaji, Hirofumi; Nishida, Erika; Miyata, Saori; Kato, Akihito; Tateyama, Akito; Furihata, Tomokazu; Shitomi, Kanako; Iwanaga, Toshihiko; Sugaya, Tsutomu

2018-01-01

The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy.

Non-invasive photo acoustic approach for human bone diagnosis.

PubMed

Thella, Ashok Kumar; Rizkalla, James; Helmy, Ahdy; Suryadevara, Vinay Kumar; Salama, Paul; Rizkalla, Maher

2016-12-01

The existing modalities of bone diagnosis including X-ray and ultrasound may cite drawback in some cases related to health issues and penetration depth, while the ultrasound modality may lack image quality. Photo acoustic approach however, provides light energy to the acoustic wave, enabling it to activate and respond according to the propagating media (which is type of bones in this case). At the same time, a differential temperature change may result in the bio heat response, resulting from the heat absorbed across the multiple materials under study. In this work, we have demonstrated the features of using photo acoustic modality in order to non-invasively diagnose the type of human bones based on their electrical, thermal, and acoustic properties that differentiate the output response of each type. COMSOL software was utilized to combine both acoustic equations and bio heat equations, in order to study both the thermal and acoustic responses through which the differential diagnosis can be obtained. In this study, we solved both the acoustic equation and bio heat equations for four types of bones, bone (cancellous), bone (cortical), bone marrow (red), and bone marrow (yellow). 1 MHz acoustic source frequency was chosen and 10(5) W/m(2) power source was used in the simulation. The simulation tested the dynamic response of the wave over a distance of 5 cm from each side for the source. Near 2.4 cm was detected from simulation from each side of the source with a temperature change of within 0.5 K for various types of bones, citing a promising technique for a practical model to detect the type of bones via the differential temperature as well as the acoustic was response via the multiple materials associated with the human bones (skin and blood). The simulation results suggest that the PA technique may be applied to non-invasive diagnosis for the different types of bones, including cancerous bones. A practical model for detecting both the temperature change via IR sensors, and acoustic wave signals may be detected via sensitive pressure transducer, which is reserved for future realization.

Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm.

PubMed

Fewtrell, Mary S; Williams, Jane E; Singhal, Atul; Murgatroyd, Peter R; Fuller, Nigel; Lucas, Alan

2009-07-01

Preterm infants are at risk of metabolic bone disease due to inadequate mineral intake with unknown consequences for later bone health. To test the hypotheses that (1) early diet programs peak bone mass and bone turnover; (2) human milk has a beneficial effect on these outcomes; (3) preterm subjects have reduced peak bone mass compared to population reference data. 20 year follow-up of 202 subjects (43% male; 24% of survivors) who were born preterm and randomized to: (i) preterm formula versus banked breast milk or (ii) preterm versus term formula; as sole diet or supplement to maternal milk. Outcome measures were (i) anthropometry; (ii) hip, lumbar spine (LS) and whole body (WB) bone mineral content (BMC) and bone area (BA) measured using DXA; (iii) bone turnover markers. Infant dietary randomization group did not influence peak bone mass or turnover. The proportion of human milk in the diet was significantly positively associated with WBBA and BMC. Subjects receiving >90% human milk had significantly higher WBBA (by 3.5%, p=0.01) and BMC (by 4.8%, p=0.03) than those receiving <10%. Compared to population data, subjects had significantly lower height SDS (-0.41 (SD 1.05)), higher BMI SDS (0.31 (1.33)) and lower LSBMD SDS (-0.29 (1.16)); height and bone mass deficits were greatest in those born SGA with birthweight <1250 g (height SDS -0.81 (0.95), LSBMD SDS -0.61 (1.3)). Infant dietary randomization group did not affect peak bone mass or turnover suggesting the observed reduced final height and LS bone mass, most marked in growth restricted subjects with the lowest birthweight, may not be related to sub-optimal early nutrition. The higher WB bone mass associated with human milk intake, despite its low nutrient content, may reflect non-nutritive factors in breast milk. These findings may have implications for later osteoporosis risk and require further investigation.

Use of DSC and DMA Techniques to Help Investigate a Material Anomaly for PTFE Used in Processing a Piston Cup for the Urine Processor Assembly (UPA) on International Space Station (ISS)

NASA Technical Reports Server (NTRS)

Wingard, Doug

2010-01-01

Human urine and flush water are eventually converted into drinking water with the Urine Processor Assembly (UPA) aboard the International Space Station (ISS). This conversion is made possible through the Distillation Assembly (DA) of the UPA. One component of the DA is a molded circular piston cup made of virgin polytetrafluoroethylene (PTFE). The piston cup is assembled to a titanium component using eight fasteners and washers. Molded PTFE produced for spare piston cups in the first quarter of 2010 was different in appearance and texture, and softer than material molded for previous cups. For the suspect newer PTFE material, cup fasteners were tightened to only one-half the required torque value, yet the washers embedded almost halfway into the material. The molded PTFE used in the DA piston cup should be Type II, based on AMS 3667D and ASTM D4894 specifications. The properties of molded PTFE are considerably different between Type I and II materials. Engineers working with the DA thought that if Type I PTFE was molded by mistake instead of Type II material, that could have resulted in the anomalous material properties. Typically, the vendor molds flat sheet PTFE from the same material lot used to mold the piston cups, and tensile testing as part of quality control should verify that the PTFE is Type II material. However, for this discrepant lot of material, such tensile data was not available. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) were two of the testing techniques used at the NASA/Marshall Space Flight Center (MSFC) to investigate the anomaly for the PTFE material. Other techniques used on PTFE specimens were: Shore D hardness testing, tensile testing on dog bone specimens and a qualitative estimation of porosity by optical and scanning electron microscopy.

A Comparison of Bone Marrow and Cord Blood Mesenchymal Stem Cells for Cartilage Self-Assembly.

PubMed

White, Jamie L; Walker, Naomi J; Hu, Jerry C; Borjesson, Dori L; Athanasiou, Kyriacos A

2018-04-02

Joint injury is a common cause of premature retirement for the human and equine athlete alike. Implantation of engineered cartilage offers the potential to increase the success rate of surgical intervention and hasten recovery times. Mesenchymal stem cells (MSCs) are a particularly attractive cell source for cartilage engineering. While bone marrow-derived MSCs (BM-MSCs) have been most extensively characterized for musculoskeletal tissue engineering, studies suggest that cord blood MSCs (CB-MSCs) may elicit a more robust chondrogenic phenotype. The objective of this study was to determine a superior equine MSC source for cartilage engineering. MSCs derived from bone marrow or cord blood were stimulated to undergo chondrogenesis through aggregate redifferentiation and used to generate cartilage through the self-assembling process. The resulting neocartilage produced from either BM-MSCs or CB-MSCs was compared by measuring mechanical, biochemical, and histological properties. We found that while BM constructs possessed higher tensile properties and collagen content, CB constructs had superior compressive properties comparable to that of native tissue and higher GAG content. Moreover, CB constructs had alkaline phosphatase activity, collagen type X, and collagen type II on par with native tissue suggesting a more hyaline cartilage-like phenotype. In conclusion, while both BM-MSCs and CB-MSCs were able to form neocartilage, CB-MSCs resulted in tissue more closely resembling native equine articular cartilage as determined by a quantitative functionality index. Therefore, CB-MSCs are deemed a superior source for the purpose of articular cartilage self-assembly.

Human umbilical cord mesenchymal stromal cells in a sandwich approach for osteochondral tissue engineering

PubMed Central

Wang, Limin; Zhao, Liang; Detamore, Michael S.

2013-01-01

Cell sources and tissue integration between cartilage and bone regions are critical to successful osteochondral regeneration. In this study, human umbilical cord mesenchymal stromal cells (hUCMSCs), derived from Wharton’s jelly, were introduced to the field of osteochondral tissue engineering and a new strategy for osteochondral integration was developed by sandwiching a layer of cells between chondrogenic and osteogenic constructs before suturing them together. Specifically, hUCMSCs were cultured in biodegradable poly-l-lactic acid scaffolds for 3 weeks in either chondrogenic or osteogenic medium to differentiate cells toward cartilage or bone lineages, respectively. A highly concentrated cell solution containing undifferentiated hUCMSCs was pasted onto the surface of the bone layer at week 3 and the two layers were then sutured together to form an osteochondral composite for another 3 week culture period. Chondrogenic and osteogenic differentiation was initiated during the first 3 weeks, as evidenced by the expression of type II collagen and runt-related transcription factor 2 genes, respectively, and continued with the increase of extracellular matrix during the last 3 weeks. Histological and immunohistochemical staining, such as for glycosaminoglycans, type I collagen and calcium, revealed better integration and transition of these matrices between two layers in the composite group containing sandwiched cells compared to other control composites. These results suggest that hUCMSCs may be a suitable cell source for osteochondral regeneration, and the strategy of sandwiching cells between two layers may facilitate scaffold and tissue integration. PMID:21953869

Fingerprinting of HLA class I genes for improved selection of unrelated bone marrow donors.

PubMed

Martinelli, G; Farabegoli, P; Buzzi, M; Panzica, G; Zaccaria, A; Bandini, G; Calori, E; Testoni, N; Rosti, G; Conte, R; Remiddi, C; Salvucci, M; De Vivo, A; Tura, S

1996-02-01

The degree of matching of HLA genes between the selected donor and recipient is an important aspect of the selection of unrelated donors for allogeneic bone marrow transplantation (UBMT). The most sensitive methods currently used are serological typing of HLA class I genes, mixed lymphocyte culture (MLC), IEF and molecular genotyping of HLA class II genes by direct sequencing of PCR products. Serological typing of class I antigenes (A, B and C) fails to detect minor differences demonstrated by direct sequencing of DNA polymorphic regions. Molecular genotyping of HLA class I genes by DNA analysis is costly and work-intensive. To improve compatibility between donor and recipient, we have set up a new rapid and non-radioisotopic application of the 'fingerprinting PCR' technique for the analysis of the polymorphic second exon of the HLA class I A, B and C genes. This technique is based on the formation of specific patterns (PCR fingerprints) of homoduplexes and heteroduplexes between heterologous amplified DNA sequences. After an electrophoretic run on non-denaturing polyacrylamide gel, different HLA class I types give allele-specific banding patterns. HLA class I matching is performed, after the gel has been soaked in ethidium bromide or silver-stained, by visual comparison of patients' fingerprints with those of donors. Identity can be confirmed by mixing donor and recipient DNAs in an amplification cross-match. To assess the technique, 10 normal samples, 22 related allogeneic bone marrow transplanted pairs and 10 unrelated HLA-A and HLA-B serologically matched patient-donor pairs were analysed for HLA class I polymorphic regions. In all the related pairs and in 1/10 unrelated pairs, matched donor-recipient patterns were identified. This new application of PCR fingerprinting may confirm the HLA class I serological selection of unrelated marrow donors.

Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen

PubMed Central

Schwarze, Ulrike; Cundy, Tim; Pyott, Shawna M.; Christiansen, Helena E.; Hegde, Madhuri R.; Bank, Ruud A.; Pals, Gerard; Ankala, Arunkanth; Conneely, Karen; Seaver, Laurie; Yandow, Suzanne M.; Raney, Ellen; Babovic-Vuksanovic, Dusica; Stoler, Joan; Ben-Neriah, Ziva; Segel, Reeval; Lieberman, Sari; Siderius, Liesbeth; Al-Aqeel, Aida; Hannibal, Mark; Hudgins, Louanne; McPherson, Elizabeth; Clemens, Michele; Sussman, Michael D.; Steiner, Robert D.; Mahan, John; Smith, Rosemarie; Anyane-Yeboa, Kwame; Wynn, Julia; Chong, Karen; Uster, Tami; Aftimos, Salim; Sutton, V. Reid; Davis, Elaine C.; Kim, Lammy S.; Weis, Mary Ann; Eyre, David; Byers, Peter H.

2013-01-01

Although biallelic mutations in non-collagen genes account for <10% of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes. We identified mutations in FKBP10, which encodes the 65 kDa prolyl cis–trans isomerase, FKBP65, in 38 members of 21 families with OI. These include 10 families from the Samoan Islands who share a founder mutation. Of the mutations, three are missense; the remainder either introduce premature termination codons or create frameshifts both of which result in mRNA instability. In four families missense mutations result in loss of most of the protein. The clinical effects of these mutations are short stature, a high incidence of joint contractures at birth and progressive scoliosis and fractures, but there is remarkable variability in phenotype even within families. The loss of the activity of FKBP65 has several effects: type I procollagen secretion is slightly delayed, the stabilization of the intact trimer is incomplete and there is diminished hydroxylation of the telopeptide lysyl residues involved in intermolecular cross-link formation in bone. The phenotype overlaps with that seen with mutations in PLOD2 (Bruck syndrome II), which encodes LH2, the enzyme that hydroxylates the telopeptide lysyl residues. These findings define a set of genes, FKBP10, PLOD2 and SERPINH1, that act during procollagen maturation to contribute to molecular stability and post-translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result. PMID:22949511

Characterization of mesenchymal stem cells and fibrochondrocytes in three-dimensional co-culture: analysis of cell shape, matrix production, and mechanical performance.

PubMed

McCorry, Mary Clare; Puetzer, Jennifer L; Bonassar, Lawrence J

2016-03-12

Bone marrow mesenchymal stem cells (MSCs) have shown positive therapeutic effects for meniscus regeneration and repair. Preliminary in vitro work has indicated positive results for MSC applications for meniscus tissue engineering; however, more information is needed on how to direct MSC behavior. The objective of this study was to examine the effect of MSC co-culture with primary meniscal fibrochondrocytes (FCCs) in a three-dimensional collagen scaffold in fibrochondrogenic media. Co-culture of MSCs and FCCs was hypothesized to facilitate the transition of MSCs to a FCC cell phenotype as measured by matrix secretion and morphology. MSCs and FCCs were isolated from bovine bone marrow and meniscus, respectively. Cells were seeded in a 20 mg/mL high-density type I collagen gel at MSC:FCC ratios of 0:100, 25:75, 50:50, 75:25, and 100:0. Constructs were cultured for up to 2 weeks and then analyzed for cell morphology, glycosaminoglycan content, collagen content, and production of collagen type I, II, and X. Cells were homogeneously mixed throughout the scaffold and cells had limited direct cell-cell contact. After 2 weeks in culture, MSCs transitioned from a spindle-like morphology toward a rounded phenotype, while FCCs remained rounded throughout culture. Although MSC shape changed with culture, the overall size was significantly larger than FCCs throughout culture. While 75:25 and 100:0 (MSC mono-culture) culture groups produced significantly more glycosaminoglycan (GAG)/DNA than FCCs in mono-culture, GAG retention was highest in 50:50 co-cultures. Similarly, the aggregate modulus was highest in 100:0 and 50:50 co-cultures. All samples contained both collagen types I and II after 2 weeks, and collagen type X expression was evident only in MSC mono-culture gels. MSCs shift to a FCC morphology in both mono- and co-culture. Co-culture reduced hypertrophy by MSCs, indicated by collagen type X. This study shows that MSC phenotype can be influenced by indirect homogeneous cell culture in a three-dimensional gel, demonstrating the applicability of MSCs in meniscus tissue engineering applications.

A novel FGFR3-binding peptide inhibits FGFR3 signaling and reverses the lethal phenotype of mice mimicking human thanatophoric dysplasia

PubMed Central

Jin, Min; Yu, Ying; Qi, Huabing; Xie, Yangli; Su, Nan; Wang, Xiaofeng; Tan, Qiaoyan; Luo, Fengtao; Zhu, Ying; Wang, Quan; Du, Xiaolan; Xian, Cory J.; Liu, Peng; Huang, Haiyang; Shen, Yue; Deng, Chu-Xia; Chen, Di; Chen, Lin

2012-01-01

Gain-of-function mutations in fibroblast growth factor receptor-3 (FGFR3) lead to several types of human skeletal dysplasia syndromes including achondroplasia, hypochondroplasia and thanatophoric dysplasia (TD). Currently, there are no effective treatments for these skeletal dysplasia diseases. In this study, we screened, using FGFR3 as a bait, a random 12-peptide phage library and obtained 23 positive clones that share identical amino acid sequences (VSPPLTLGQLLS), named as peptide P3. This peptide had high binding specificity to the extracellular domain of FGFR3. P3 inhibited tyrosine kinase activity of FGFR3 and its typical downstream molecules, extracellular signal-regulated kinase/mitogen-activated protein kinase. P3 also promoted proliferation and chondrogenic differentiation of cultured ATDC5 chondrogenic cells. In addition, P3 alleviated the bone growth retardation in bone rudiments from mice mimicking human thanatophoric dysplasia type II (TDII). Finally, P3 reversed the neonatal lethality of TDII mice. Thus, this study identifies a novel inhibitory peptide for FGFR3 signaling, which may serve as a potential therapeutic agent for the treatment of FGFR3-related skeletal dysplasia. PMID:23014564

Bone morphology changes around two types of bone-level implants installed in fresh extraction sockets--a histomorphometric study in Beagle dogs.

PubMed

Alharbi, Hend M; Babay, Nadir; Alzoman, Hamad; Basudan, Sumaya; Anil, Sukumaran; Jansen, John A

2015-09-01

Minimizing crestal bone loss following immediate implant placement is considered the most challenging aspect in implant therapy. Implant surface topography and chemical modifications have been shown to influence the success of Osseointegration. The Straumann Bone Level implant, featuring SLActive surface, has been introduced with the aim of enhancing bone apposition. Similarly, the OsseoSpeed implants from Astra Tech claim to have an enhanced osseointegration. Because of the specific features in the implant design, both companies claim that crestal resorption is minimal with these implants. To evaluate the osseointegration and crestal bone level following immediate placement of Straumann Bone Level implant and OsseoSpeed implants in fresh extraction sockets in Beagle dogs. The distal roots of the second, third and fourth premolars were extracted in both sides of the mandible. The distal roots were removed using a dental elevator. A total of 60 fixtures were installed in 10 Beagle dogs. Two types of implants were used: Straumann Bone-Level implants, which were 8 × 3.3 mm in size, and Astra Tech OsseoSpeed 3.5 S MicroThread implants, which were 8 × 3.5 mm in size. The histomorphometrical evaluation was performed at the end of 4- and 12-week healing. The implant-bone contact and bone volume percentage were assessed. The bone-to-implant contact (BIC) and the bone volume did not show any significant changes for both types of implants. The OsseoSpeed™ implants showed 67.4% and 65.3% BIC, respectively, at 4 and 12 weeks compared with 71.7 and 73.1 for the Straumann Bone-Level implants. The bone volume around both types of implants did not differ significantly at both time periods. The crestal bone resorption was observed for both types of implants. The first BIC at buccal side and lingual side of the implants also did not differ significantly for both implant systems. This study showed that Straumann Bone Level and OsseoSpeed implants induced similar bone response after immediate implantation at 4 and 12 weeks. The immediate implant placement resulted in peri-implant crestal bone-level changes for both types of implants. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

21 CFR 888.3353 - Hip joint metal/ceramic/polymer semi-constrained cemented or nonporous uncemented prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... fixed in the intramedullary canal of the femur by impaction with or without use of bone cement. The... nonporous metal alloys, and used with or without bone cement. (b) Classification. Class II. [54 FR 48239...

21 CFR 888.3353 - Hip joint metal/ceramic/polymer semi-constrained cemented or nonporous uncemented prosthesis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... fixed in the intramedullary canal of the femur by impaction with or without use of bone cement. The... nonporous metal alloys, and used with or without bone cement. (b) Classification. Class II. [54 FR 48239...

21 CFR 888.3353 - Hip joint metal/ceramic/polymer semi-constrained cemented or nonporous uncemented prosthesis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... fixed in the intramedullary canal of the femur by impaction with or without use of bone cement. The... nonporous metal alloys, and used with or without bone cement. (b) Classification. Class II. [54 FR 48239...

21 CFR 888.3353 - Hip joint metal/ceramic/polymer semi-constrained cemented or nonporous uncemented prosthesis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... fixed in the intramedullary canal of the femur by impaction with or without use of bone cement. The... nonporous metal alloys, and used with or without bone cement. (b) Classification. Class II. [54 FR 48239...

21 CFR 888.3353 - Hip joint metal/ceramic/polymer semi-constrained cemented or nonporous uncemented prosthesis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... fixed in the intramedullary canal of the femur by impaction with or without use of bone cement. The... nonporous metal alloys, and used with or without bone cement. (b) Classification. Class II. [54 FR 48239...

Identification of Skeletal Remains of Communist Armed Forces Victims During and After World War II: Combined Y-chromosome Short Tandem Repeat (STR) and MiniSTR Approach

PubMed Central

Marjanović, Damir; Durmić-Pašić, Adaleta; Kovačević, Lejla; Avdić, Jasna; Džehverović, Mirela; Haverić, Sanin; Ramić, Jasmin; Kalamujić, Belma; Bilela, Lada Lukić; Škaro, Vedrana; Projić, Petar; Bajrović, Kasim; Drobnič, Katja; Davoren, Jon; Primorac, Dragan

2009-01-01

Aim To report on the use of STR, Y-STRs, and miniSTRs typing methods in the identification of victims of revolutionary violence and crimes against humanity committed by the Communist Armed Forces during and after World War II in which bodies were exhumed from mass and individual graves in Slovenia. Methods Bone fragments and teeth were removed from human remains found in several small and closely located hidden mass graves in the Škofja Loka area (Lovrenska Grapa and Žolšče) and 2 individual graves in the Ljubljana area (Podlipoglav), Slovenia. DNA was isolated using the Qiagen DNA extraction procedure optimized for bone and teeth. Some DNA extracts required additional purification, such as N-buthanol treatment. The QuantifilerTM Human DNA Quantification Kit was used for DNA quantification. Initially, PowerPlex 16 kit was used to simultaneously analyze 15 short tandem repeat (STR) loci. The PowerPlex S5 miniSTR kit and AmpFℓSTR® MiniFiler PCR Amplification Kit was used for additional analysis if preliminary analysis yielded weak partial or no profiles at all. In 2 cases, when the PowerPlex 16 profiles indicated possible relatedness of the remains with reference samples, but there were insufficient probabilities to call the match to possible male paternal relatives, we resorted to an additional analysis of Y-STR markers. PowerPlex® Y System was used to simultaneously amplify 12 Y-STR loci. Fragment analysis was performed on an ABI PRISM 310 genetic analyzer. Matching probabilities were estimated using the DNA-View software. Results Following the Y-STR analysis, 1 of the “weak matches” previously obtained based on autosomal loci, was confirmed while the other 1 was not. Combined standard STR and miniSTR approach applied to bone samples from 2 individual graves resulted in positive identifications. Finally, using the same approach on 11 bone samples from hidden mass grave Žološče, we were able to obtain 6 useful DNA profiles. Conclusion The results of this study, in combination with previously obtained results, demonstrate that Y-chromosome testing and miniSTR methodology can contribute to the identification of human remains of victims of revolutionary violence from World War II. PMID:19480024

Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer.

PubMed

Roy, Lopamudra Das; Ghosh, Sriparna; Pathangey, Latha B; Tinder, Teresa L; Gruber, Helen E; Mukherjee, Pinku

2011-08-22

Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in arthritic PyV MT mice. This was further substantiated by treatment with celecoxib, an anti-inflammatory drug + αIL-17 antibody that significantly reduced the secondary metastasis to lung and bone. The data generated not only reveal the underlying mechanism of high susceptibility to bone and lung metastasis in an arthritic condition but our combination therapies may lead to treatment modalities that will be capable of reducing tumor burden, and preventing relapse and metastasis in arthritic patients with breast cancer.

Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

PubMed Central

2011-01-01

Background Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. Methods To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. Results A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in arthritic PyV MT mice. This was further substantiated by treatment with celecoxib, an anti-inflammatory drug + αIL-17 antibody that significantly reduced the secondary metastasis to lung and bone. Conclusions The data generated not only reveal the underlying mechanism of high susceptibility to bone and lung metastasis in an arthritic condition but our combination therapies may lead to treatment modalities that will be capable of reducing tumor burden, and preventing relapse and metastasis in arthritic patients with breast cancer. PMID:21859454

Negligence claims following non-union and malunion of long bone fractures: An analysis of 15 years of data.

PubMed

Metcalfe, C W; Harrison, W D; Nayagam, S; Narayan, B

2016-10-01

Non-unions and malunions are recognised to be complications of the treatment of long bone fractures. No previous work has looked at the implications of these complications from a medicolegal perspective. A complete database of litigation claims in Trauma and Orthopaedic Surgery was obtained from the NHS Litigation Authority. Two separate modalities of the treatment of long bone fractures were examined i) non-union and ii) acquired deformity. The type of complaint, whether defended or not, and costs were analysed. There were claims of which 97 related to non-union and 32 related to postoperative limb deformity. The total cost was £8.2 million over a 15-year period in England and Wales. Femoral and tibial non-unions were more expensive particularly if they resulted in amputation. Rotational deformity cost nearly twice as much as angulation deformities. The cosmetic appearances of rotational malalignment and amputation results in higher compensation; this reinforces an outward perception of outcome as being more important than harmful effects. Notwithstanding the limitations of this database, there are clinical lessons to be gained from these litigation claims. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Osteogenic properties of a short BMP-2 chimera peptide.

PubMed

Falcigno, Lucia; D'Auria, Gabriella; Calvanese, Luisa; Marasco, Daniela; Iacobelli, Roberta; Scognamiglio, Pasqualina L; Brun, Paola; Danesin, Roberta; Pasqualin, Matteo; Castagliuolo, Ignazio; Dettin, Monica

2015-09-01

Bone morphogenetic proteins (BMPs) play a key role in bone and cartilage formation. For these properties, BMPs are employed in the field of tissue engineering to induce bone regeneration in damaged tissues. To overcome drawbacks due to the use of entire proteins, synthetic peptides derived from their parent BMPs have come out as promising molecules for biomaterial design. On the structural ground of the experimental BMP-2 receptor complexes reported in the literature, we designed three peptides, reproducing the BMP-2 region responsible for the binding to the type II receptor, ActRIIB. These peptides were characterized by NMR, and the structural features of the peptide-receptor binding interface were highlighted by docking experiments. Peptide-receptor binding affinities were analyzed by means of ELISA and surface plasmon resonance techniques. Furthermore, cellular assays were performed to assess their osteoinductive properties. A chimera peptide, obtained by combining the sequence portions 73-92 and 30-34 of BMP-2, shows the best affinity for ActRIIB in the series and represents a good starting point for the design of new compounds able to reproduce osteogenic properties of the parent BMP-2. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

Denosumab treatment of prostate cancer with bone metastases and increased urine N-telopeptide levels after therapy with intravenous bisphosphonates: results of a randomized phase II trial.

PubMed

Fizazi, Karim; Bosserman, Linda; Gao, Guozhi; Skacel, Tomas; Markus, Richard

2013-01-01

Patients with bone metastases have high rates of RANKL driven bone resorption and an increased risk of skeletal morbidity. Osteoclast mediated bone resorption can be assessed by measuring urine N-telopeptide and can be inhibited by denosumab, a fully human antibody against RANKL. Eligible patients (111) had bone metastases from prostate cancer, other solid tumors or multiple myeloma, 1 or more bone lesions and urine N-telopeptide greater than 50 nM bone collagen equivalents per mM creatinine (urine N-telopeptide greater than 50) despite the use of intravenous bisphosphonates. Patients were stratified by cancer type and screening urine N-telopeptide, and randomized to continue intravenous bisphosphonates every 4 weeks or receive 180 mg subcutaneous denosumab every 4 weeks or 180 mg every 12 weeks. The primary end point was the proportion of patients with urine N-telopeptide less than 50 at week 13. We report the efficacy results for the subset of patients with prostate cancer. Patients with prostate cancer represented 45% (50 of 111) of the study population. At week 13, 22 of 32 (69%) patients in the denosumab arms had urine N-telopeptide less than 50 vs 3 of 16 (19%) in the intravenous bisphosphonates cohort. At week 25, 22 of 32 (69%) denosumab treated patients continued to have urine N-telopeptide less than 50 vs 5 of 16 (31%) treated with intravenous bisphosphonates. Grade 4, asymptomatic, reversible hypophosphatemia, possibly related to denosumab, was reported in 1 patient. In patients with prostate cancer related bone metastases and increased urine N-telopeptide despite intravenous bisphosphonate treatment, denosumab normalized urine N-telopeptide levels more frequently than ongoing intravenous bisphosphonates. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Insulin resistance and bone strength: findings from the study of midlife in the United States.

PubMed

Srikanthan, Preethi; Crandall, Carolyn J; Miller-Martinez, Dana; Seeman, Teresa E; Greendale, Gail A; Binkley, Neil; Karlamangla, Arun S

2014-04-01

Although several studies have noted increased fracture risk in individuals with type 2 diabetes mellitus (T2DM), the pathophysiologic mechanisms underlying this association are not known. We hypothesize that insulin resistance (the key pathology in T2DM) negatively influences bone remodeling and leads to reduced bone strength. Data for this study came from 717 participants in the Biomarker Project of the Midlife in the United States Study (MIDUS II). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting morning blood glucose and insulin levels. Projected 2D (areal) bone mineral density (BMD) was measured in the lumbar spine and left hip using dual-energy X-ray absorptiometry (DXA). Femoral neck axis length and width were measured from the hip DXA scans, and combined with BMD and body weight and height to create composite indices of femoral neck strength relative to load in three different failure modes: compression, bending, and impact. We used multiple linear regressions to examine the relationship between HOMA-IR and bone strength, adjusted for age, gender, race/ethnicity, menopausal transition stage (in women), and study site. Greater HOMA-IR was associated with lower values of all three composite indices of femoral neck strength relative to load, but was not associated with BMD in the femoral neck. Every doubling of HOMA-IR was associated with a 0.34 to 0.40 SD decrement in the strength indices (p<0.001). On their own, higher levels of fasting insulin (but not of glucose) were independently associated with lower bone strength. Our study confirms that greater insulin resistance is related to lower femoral neck strength relative to load. Further, we note that hyperinsulinemia, rather than hyperglycemia, underlies this relationship. Although cross-sectional associations do not prove causality, our findings do suggest that insulin resistance and in particular, hyperinsulinemia, may negatively affect bone strength relative to load. © 2014 American Society for Bone and Mineral Research.

[Surgical strategy for upper cervical vertebrae instability through the anterior approach].

PubMed

Huang, Wei-bing; Cai, Xian-hua; Chen, Zhuang-hong; Huang, Ji-feng; Liu, Xi-ming; Wei, Shi-jun

2013-07-01

To explore the choice and effect of internal fixation in treating upper cervical vertebrae instability through anterior approach. From March 2000 to September 2010,83 patients with upper cervical vertebrae instability were treated with internal fixation through anterior approach. There were 59 males and 24 females with a mean age of 42 years old (ranged, 20 to 68). Among these patients, 36 patients were treated with odontoid screw fixation, 16 patients with C1,2 transarticular screw fixation, 23 patients with C2,3 steel plate fixation, 5 patients with odontoid screw and transarticular screw fixation,2 patients with odontoid screw and C2.3 steel plate fixation, 1 patient with C1,2 transarticular screw and C2,3 steel plate fixation. One patient with completely cervical vertebrae cord injury died of pulmonary infection after C1,2 transarticular screw fixation. Other patients were followed up from 8 to 36 months with an average of 15 months. Upper cervical vertebrae stability were restored without vertebral artery and spinal cord injury. Thirty-six patients were treated with odontoid screw fixation and 5 patients were treated with screw combined with transarticular screw fixation obtained bone union in the dentations without bone graft. Among the 16 patients treated with C1,2 transarticular screw fixation, 13 patients obtained bone union after bone graft; 1 patient died of pulmonary infection after surgery; 1 patient with comminuted odontoid fracture of type II C and atlantoaxial anterior dislocation did not obtain bone union after bone graft,but the fibrous healing was strong enough to maintain the atlantoaixal joint stability; 1 patient with obsolete atlantoaxial anterior dislocation were re-treated with Brooks stainless steel wire fixation and bone graft through posterior approach, and finally obtained bone union. It could obtain satisfactory effects depending on the difference of cervical vertebrae instability to choose the correctly surgical method.

Osteogenesis Imperfecta: A Case Report and Review of Literature

PubMed Central

Edelu, BO; Ndu, IK; Asinobi, IN; Obu, HA; Adimora, GN

2014-01-01

Osteogenesis imperfecta (OI) is a group of rare inherited disorders of connective tissue with the common feature of excessive fragility of bones caused by mutations in collagen. Diagnosis is mainly based on the clinical features of the disorder. We report, the case of a male neonate delivered to a 33-year-old para 2 female at University of Nigeria Teaching Hospital, Enugu with no family history suggestive of OI. He had clinical features of a type II OI and severe birth asphyxia. Multidisciplinary management was instituted, but he died on the 7th day of life. PMID:25031897

Vaccinia Virus Blocks Stat1-Dependent and Stat1-Independent Gene Expression Induced by Type I and Type II Interferons

PubMed Central

Mann, Brandon A.; Huang, Julia He; Li, Ping; Chang, Hua-Chen; Slee, Roger B.; O'Sullivan, Audrey; Mathur, Anita; Yeh, Norman; Klemsz, Michael J.; Brutkiewicz, Randy R.; Blum, Janice S.

2008-01-01

Blocking the function of Stat (signal transducer and activator of transcription) proteins, which are critical for antiviral responses, has evolved as a common mechanism for pathogen immune evasion. The poxvirus-encoded phosphatase H1 is critical for viral replication, and may play an additional role in the evasion of host defense by dephosphorylating Stat1 and blocking interferon (IFN)-stimulated innate immune responses. Vaccinia virus (VACV) H1 can inhibit the phosphorylation of the transcription factor Stat1 after IFN-γ stimulation of epithelial cells, greatly attenuating IFN-induced biological functions. In this study, we demonstrate that VACV infection is capable of inhibiting the phosphorylation of Stat1 and Stat2 after stimulation of fibroblasts or bone marrow-derived macrophages with either type I or type II IFNs, but did not inhibit the activation of Stat3 or Stat5 in either cell type. By using recombinant proteins for in vitro assays, we observe that variola virus H1 is more active than VACV H1, although it has similar selectivity for Stat targets. Differential effects of VACV infection were observed on the induction of IFN-stimulated genes, with complete inhibition of some genes by VACV infection, while others were less affected. Despite the IFN-γ-induced expression of some genes in VACV-infected cells, IFN-γ was unable to rescue the VACV-mediated inhibition of MHC class II antigen presentation. Moreover, VACV infection can affect the IFN-induced expression of Stat1-dependent and Stat1-independent genes, suggesting that the virus may target additional IFN-activated pathways. Thus, VACV targets multiple signaling pathways in the evasion of antiviral immune responses. PMID:18593332

Evaluation of calabash chalk effect on femur bone morphometry and mineralization in young wistar rats: A pilot study.

PubMed

Ekong, Moses B; Ekanem, Theresa B; Sunday, Abraham O; Aquaisua, Aquaisua N; Akpanabiatu, Monday I

2012-07-01

Calabash chalk, a popularly consumed geophagic material in Nigeria has been reported to contain lead, arsenic, alpha lindane, endrin, and endosulfan 11 among other pollutants. The continuous exposure of young children to this chalk necessitated this study on the bone morphometry and mineralization in young Wistar rats. Fourteen young (weanling) Wistar rats of both sexes weighing 54-72 g were assigned into two groups of seven animals each. Group I served as control, while group II was the test group (TG). 40 mg/ml of C. chalk was administered as suspension to the test animals in group II. Animals in the control group were orally treated with 1ml of distilled water. Administration of the C. chalk in the animals lasted for 28 days, and the animals were sacrificed on day 29, using chloroform anaesthesia. The femur bones were dissected out, cleaned of flesh and sun-dried. The lengths and weights of the femur bones were measured using graphite furnace atomic mass spectrophotometer. Results showed 1.6% decrease in body weight change in the TG, insignificant decreases in the weights and lengths of both the right and left femur bones, and significant decreased (P < 0.0126) organ-somatic index, and femur bones concentrations (mg/l) of zinc, phosphate, carbonate, calcium, sodium, and potassium (P < 0.05). In conclusion, this study showed that C. chalk may alter growth rate, and cause de-mineralization in the femur bone, hence, it may be detrimental to bone growth.

Identification of rat serum alkaline phosphatase isoenzyme by means of wheat germ agglutinin.

PubMed

Wada, H; Niwa, N; Hayakawa, T; Tsuge, H

1997-01-01

Wheat germ agglutinin (WGA) precipitates bone type serum alkaline phosphatase (sALP) isoenzyme specifically. The precipitates are composed of the macromolecules of WGA and "bone type sALP" (WGA-ALP complex). In order to use bone type sALP as a marker in polyacrylamide gel electrophoresis (PAGE), a method to separate "bone type sALP" from the "WGA-ALP complex" was established by using N-acetyl-D-glucosamine (GlcNAc)-Sepharose 6E column chromatography. It was concluded that this method is useful for clinical examination in the rat.

Bone mineralization is elevated and less heterogeneous in adults with type 2 diabetes and osteoarthritis compared to controls with osteoarthritis alone

PubMed Central

Pritchard, J.M.; Papaioannou, A.; Tomowich, C.; Giangregorio, L.M.; Atkinson, S.A.; Beattie, K.A.; Adachi, J.D.; DeBeer, J.; Winemaker, M.; Avram, V.; Schwarcz, H.P.

2016-01-01

Purpose The purpose of this study was to determine whether trabecular bone mineralization differed in adults with type 2 diabetes compared to adults without type 2 diabetes. Methods Proximal femur specimens were obtained following a total hip replacement procedure from men and women ≥65 years of age with and without type 2 diabetes. A scanning electron microscope was used for quantitative backscattered electron imaging (qBEI) analysis of trabecular bone samples from the femoral neck. Gray scale images (pixel size=5.6 μm2) were uploaded to ImageJ software and gray level (GL) values were converted to calcium concentrations (weight [wt] % calcium [Ca]) using data obtained with energy dispersive X-ray spectrometry. The following bone mineralization density distribution (BMDD) outcomes were collected: the weighted mean bone calcium concentration (CaMEAN), the most frequently occurring bone calcium concentration (CaPEAK) and mineralization heterogeneity (CaWIDTH). Differences between groups were assessed using the Student’s t-test for normally distributed data and Mann–Whitney U-test for non-normally distributed data. An alpha value of <0.05 was considered significant. Results Thirty-five Caucasian participants were recruited (mean [standard deviation, SD] age, 75.5 [6.5] years): 14 adults with type 2 diabetes (years since type 2 diabetes diagnosis, 13.5 [7.4] years) and 21 adults without type 2 diabetes. In the adults with type 2 diabetes, bone CaMEAN was 4.9% greater (20.36 [0.98] wt.% Ca versus 19.40 [1.07] wt.% Ca, p=0.015) and CaWIDTH was 9.4% lower (median [interquartile range] 3.55 [2.99–4.12] wt.% Ca versus 3.95 [0.71] wt.% Ca, p<0.001) compared to controls. There was no between-group difference in CaPEAK (21.12 [0.97] wt.% Ca for type 2 diabetes versus 20.44 [1.30] wt.% Ca for controls, p=0.121). Conclusion The combination of elevated mean calcium concentration in bone and lower mineralization heterogeneity in adults with type 2 diabetes may have deleterious effects on the biomechanical properties of bone. These microscopic alterations in bone mineralization, which may be mediated by suppressed bone remodeling, further elucidate higher fracture risk in adults with type 2 diabetes. PMID:23356988

A study on Rayleigh wave dispersion in bone according to Mindlin's Form II gradient elasticity.

PubMed

Vavva, Maria G; Gergidis, Leonidas N; Protopappas, Vasilios C; Charalambopoulos, Antonios; Polyzos, Demosthenes; Fotiadis, Dimitrios I

2014-05-01

The classical elasticity cannot effectively describe bone's mechanical behavior since only homogeneous media and local stresses are assumed. Additionally, it cannot predict the dispersive nature of the Rayleigh wave which has been reported in experimental studies and was also demonstrated in a previous computational study by adopting Mindlin's Form II gradient elasticity. In this work Mindlin's theory is employed to analytically determine the dispersion of Rayleigh waves in a strain gradient elastic half-space. An isotropic semi-infinite space is considered with properties equal to those of bone and dynamic behavior suffering from microstructural effects. Microstructural effects are considered by incorporating four intrinsic parameters in the stress analysis. The results are presented in the form of group and phase velocity dispersion curves and compared with existing computational results and semi-analytical curves calculated for a simpler case of Rayleigh waves in dipolar gradient elastic half-spaces. Comparisons are also performed with the velocity of the first-order antisymmetric mode propagating in a dipolar plate so as to observe the Rayleigh asymptotic behavior. It is shown that Mindlin's Form II gradient elasticity can effectively describe the dispersive nature of Rayleigh waves. This study could be regarded as a step toward the ultrasonic characterization of bone.

Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis.

PubMed

Lakhal, Samira; Schödel, Johannes; Townsend, Alain R M; Pugh, Christopher W; Ratcliffe, Peter J; Mole, David R

2011-02-11

Hepcidin is a liver-derived hormone with a key role in iron homeostasis. In addition to iron, it is regulated by inflammation and hypoxia, although mechanisms of hypoxic regulation remain unclear. In hepatocytes, hepcidin is induced by bone morphogenetic proteins (BMPs) through a receptor complex requiring hemojuvelin (HJV) as a co-receptor. Type II transmembrane serine proteinase (TMPRSS6) antagonizes hepcidin induction by BMPs by cleaving HJV from the cell membrane. Inactivating mutations in TMPRSS6 lead to elevated hepcidin levels and consequent iron deficiency anemia. Here we demonstrate that TMPRSS6 is up-regulated in hepatic cell lines by hypoxia and by other activators of hypoxia-inducible factor (HIF). We show that TMPRSS6 expression is regulated by both HIF-1α and HIF-2α. This HIF-dependent up-regulation of TMPRSS6 increases membrane HJV shedding and decreases hepcidin promoter responsiveness to BMP signaling in hepatocytes. Our results reveal a potential role for TMPRSS6 in hepcidin regulation by hypoxia and provide a new molecular link between oxygen sensing and iron homeostasis.

Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men?

PubMed Central

Leung, J.; Zhang, Y. F.; Bauer, D.; Ensrud, K. E.; Barrett-Connor, E.; Leung, P. C.

2013-01-01

Summary In a prospective cohort study of 5,995 older American men (MrOS), users of angiotensin-converting enzyme (ACE) inhibitors had a small but significant increase in bone loss at the hip over 4 years after adjustment for confounders. Use of angiotensin II AT1 receptor blockers (ARB) was not significantly associated with bone loss. Introduction Experimental evidence suggests that angiotensin II promotes bone loss by its effects on osteoblasts. It is therefore plausible that ACE inhibitor and ARB may reduce rates of bone loss. The objective of this study is to examine the independent effects of ACE inhibitor and ARB on bone loss in older men. Methods Out of 5,995 American men (87.2%) aged ≥65 years, 5,229 were followed up for an average of 4.6 years in a prospective six-center cohort study—The Osteoporotic Fractures in Men Study (MrOS). Bone mineral densities (BMD) at total hip, femoral neck, and trochanter were measured by Hologic densitometer (QDR 4500) at baseline and year 4. Results Out of 3,494 eligible subjects with complete data, 1,166 and 433 subjects reported use of ACE inhibitors and ARBs, respectively. When compared with nonusers, continuous use of ACE inhibitors was associated with a small (0.004 g/cm2) but significant increase in the average rate of BMD loss at total hip and trochanter over 4 years after adjustment for confounders. Use of ARB was not significantly associated with bone loss. Conclusion Use of ACE inhibitors but not ARB may marginally increase bone loss in older men. PMID:22080379

Functionalization of deproteinized bovine bone with a coating-incorporated depot of BMP-2 renders the material efficiently osteoinductive and suppresses foreign-body reactivity.

PubMed

Wu, Gang; Hunziker, Ernst B; Zheng, Yuanna; Wismeijer, Daniel; Liu, Yuelian

2011-12-01

The repair of critical-sized bony defects remains a challenge in the fields of implantology, maxillofacial surgery and orthopaedics. As an alternative bone-defect filler to autologous bone grafts, deproteinized bovine bone (DBB) is highly osteoconductive and clinically now widely used. However, this product suffers from the disadvantage of not being intrinsically osteoinductive. In the present study, this property was conferred by coating DBB with a layer of calcium phosphate into which bone morphogenetic protein 2 (BMP-2) was incorporated. Granules of DBB bearing a coating-incorporated depot of BMP-2--together with the appropriate controls (DBB bearing a coating but no BMP-2; uncoated DBB bearing adsorbed BMP-2; uncoated DBB bearing no BMP-2)--were implanted subcutaneously in rats. Five weeks later, the implants were withdrawn for a histomorphometric analysis of the volume densities of (i) bone, (ii) bone marrow, (iii) foreign-body giant cells and (iv) fibrous capsular tissue. Parameters (i) and (ii) were highest, whilst parameters (iii) and (iv) were lowest in association with DBB bearing a coating-incorporated depot of BMP-2. Hence, this mode of functionalization not only confers DBB with the property of osteoinductivity but also improves its biocompatibility--thus dually enhancing its clinical potential in the repair of bony defects. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of boning method and postmortem aging on meat quality characteristics of pork loin.

PubMed

Li, Chunbao; Wu, Juqing; Zhang, Nan; Zhang, Song; Liu, Juan; Li, Jinping; Li, Hongmin; Feng, Xianchao; Han, Yanqing; Zhu, Zhiyuan; Xu, Xinglian; Zhou, Guanghong

2009-10-01

This work investigated the effects of boning method and postmortem aging on pork loin color, shearing value and sensory attributes. Two experiments were assigned. In Experiment I, 30 Chinese native black pigs were slaughtered and their carcasses were divided into three groups: (i) hot-boning: carcasses were fabricated within 45 min postmortem just after dressing; (ii) cold boning at 24 h: carcasses were fabricated after chilling at 0 degrees C for 24 h; (iii) cold boning at 36 h: carcasses were fabricated after chilling at 0 degrees C for 36 h. In Experiment II, right sides of the second group in Experiment I were used and primal cuts were vacuum packed and aged for 1 day, 8 days and 16 days. Pork loins (Longissimus lumborum) were used for color measurement, shearing test, and sensory evaluation. Among three boning methods, cold-boning at 36 h postmortem had the advantages of giving muscles a better color, the lowest cooking loss and cooked shearing value, and the highest sensory tenderness, juiciness, flavor and overall liking. Postmortem aging could improve pork quality characteristics, but it is not the fact that the longer aging time is, the better pork quality would be. Eight days may be enough to obtain an acceptable sensory attribute. These results are meaningful for pork processing and pork consumption.

Collagen Scaffolds in Bone Sialoprotein-Mediated Bone Regeneration

PubMed Central

Kruger, Thomas E.; Miller, Andrew H.; Wang, Jinxi

2013-01-01

Decades of research in bioengineering have resulted in the development of many types of 3-dimentional (3D) scaffolds for use as drug delivery systems (DDS) and for tissue regeneration. Scaffolds may be comprised of different natural fibers and synthetic polymers as well as ceramics in order to exert the most beneficial attributes including biocompatibility, biodegradability, structural integrity, cell infiltration and attachment, and neovascularization. Type I collagen scaffolds meet most of these criteria. In addition, type I collagen binds integrins through RGD and non-RGD sites which facilitates cell migration, attachment, and proliferation. Type I collagen scaffolds can be used for bone tissue repair when they are coated with osteogenic proteins such as bone morphogenic protein (BMP) and bone sialoprotein (BSP). BSP, a small integrin-binding ligand N-linked glycoprotein (SIBLING), has osteogenic properties and plays an essential role in bone formation. BSP also mediates mineral deposition, binds type I collagen with high affinity, and binds αvβ 3 and αvβ 5 integrins which mediate cell signaling. This paper reviews the emerging evidence demonstrating the efficacy of BSP-collagen scaffolds in bone regeneration. PMID:23653530

Collagen scaffolds in bone sialoprotein-mediated bone regeneration.

PubMed

Kruger, Thomas E; Miller, Andrew H; Wang, Jinxi

2013-01-01

Decades of research in bioengineering have resulted in the development of many types of 3-dimentional (3D) scaffolds for use as drug delivery systems (DDS) and for tissue regeneration. Scaffolds may be comprised of different natural fibers and synthetic polymers as well as ceramics in order to exert the most beneficial attributes including biocompatibility, biodegradability, structural integrity, cell infiltration and attachment, and neovascularization. Type I collagen scaffolds meet most of these criteria. In addition, type I collagen binds integrins through RGD and non-RGD sites which facilitates cell migration, attachment, and proliferation. Type I collagen scaffolds can be used for bone tissue repair when they are coated with osteogenic proteins such as bone morphogenic protein (BMP) and bone sialoprotein (BSP). BSP, a small integrin-binding ligand N-linked glycoprotein (SIBLING), has osteogenic properties and plays an essential role in bone formation. BSP also mediates mineral deposition, binds type I collagen with high affinity, and binds α v β 3 and α v β 5 integrins which mediate cell signaling. This paper reviews the emerging evidence demonstrating the efficacy of BSP-collagen scaffolds in bone regeneration.

Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling.

PubMed

Mishina, Yuji; Starbuck, Michael W; Gentile, Michael A; Fukuda, Tomokazu; Kasparcova, Viera; Seedor, J Gregory; Hanks, Mark C; Amling, Michael; Pinero, Gerald J; Harada, Shun-ichi; Behringer, Richard R

2004-06-25

Bone morphogenetic proteins (BMPs) function during various aspects of embryonic development including skeletogenesis. However, their biological functions after birth are less understood. To investigate the role of BMPs during bone remodeling, we generated a postnatal osteoblast-specific disruption of Bmpr1a that encodes the type IA receptor for BMPs in mice. Mutant mice were smaller than controls up to 6 months after birth. Irregular calcification and low bone mass were observed, but there were normal numbers of osteoblasts. The ability of the mutant osteoblasts to form mineralized nodules in culture was severely reduced. Interestingly, bone mass was increased in aged mutant mice due to reduced bone resorption evidenced by reduced bone turnover. The mutant mice lost more bone after ovariectomy likely resulting from decreased osteoblast function which could not overcome ovariectomy-induced bone resorption. In organ culture of bones from aged mice, ablation of the Bmpr1a gene by adenoviral Cre recombinase abolished the stimulatory effects of BMP4 on the expression of lysosomal enzymes essential for osteoclastic bone resorption. These results demonstrate essential and age-dependent roles for BMP signaling mediated by BMPRIA (a type IA receptor for BMP) in osteoblasts for bone remodeling.

The concentration of manganese, iron and strontium in bone of red fox Vulpes vulpes (L. 1758).

PubMed

Budis, Halina; Kalisinska, Elzbieta; Lanocha, Natalia; Kosik-Bogacka, Danuta I

2013-12-01

The aims of the study were to determine manganese (Mn), iron (Fe) and strontium (Sr) concentrations in fox bone samples from north-western Poland and to examine the relationships between the bone Mn, Fe and Sr concentrations and the sex and age of the foxes. In the studied samples of fox cartilage, cartilage with adjacent compact bone, compact bone and spongy bone, the concentrations of the analysed metals had the following descending order: Fe > Sr > Mn. The only exception was in compact bone, in which the concentrations were arranged in the order Sr > Fe > Mn. Manganese concentrations were significantly higher in cartilage, compact bone and cartilage with compact bone than in spongy bone. Iron concentrations were higher in cartilage and spongy bone compared with compact bone. Strontium concentrations were greater in compact bone than in cartilage and spongy bone. The manganese, iron and strontium concentrations in the same type of bone material in many cases correlated with each other, with the strongest correlation (r > 0.70) between Mn and Fe in almost all types of samples. In addition, concentrations of the same metals in different bone materials were closely correlated for Mn and Fe in cartilage and cartilage with adjacent compact bone, and for Sr in compact bone and cartilage with compact bone. In the fox from NW Poland, there were no statistically significant differences in Mn, Fe and Sr in any of the types of bone material between the sexes and immature and adult foxes.

Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells as a Potential Source for Cartilage and Bone Regeneration: An In Vitro Study

PubMed Central

Mattia, S.; Castoldi, F.; Barbero, A.; Bonasia, D. E.; Bruzzone, M.; Dettoni, F.; Scurati, R.

2017-01-01

Umbilical cord (UC) may represent an attractive cell source for allogeneic mesenchymal stem cell (MSC) therapy. The aim of this in vitro study is to investigate the chondrogenic and osteogenic potential of UC-MSCs grown onto tridimensional scaffolds, to identify a possible clinical relevance for an allogeneic use in cartilage and bone reconstructive surgery. Chondrogenic differentiation on scaffolds was confirmed at 4 weeks by the expression of sox-9 and type II collagen; low oxygen tension improved the expression of these chondrogenic markers. A similar trend was observed in pellet culture in terms of matrix (proteoglycan) production. Osteogenic differentiation on bone-graft-substitute was also confirmed after 30 days of culture by the expression of osteocalcin and RunX-2. Cells grown in the hypertrophic medium showed at 5 weeks safranin o-positive stain and an increased CbFa1 expression, confirming the ability of these cells to undergo hypertrophy. These results suggest that the UC-MSCs isolated from minced umbilical cords may represent a valuable allogeneic cell population, which might have a potential for orthopaedic tissue engineering such as the on-demand cell delivery using chondrogenic, osteogenic, and endochondral scaffold. This study may have a clinical relevance as a future hypothetical option for allogeneic single-stage cartilage repair and bone regeneration. PMID:29358953

Promotion of osteoblast differentiation in 3D biomaterial micro-chip arrays comprising fibronectin-coated poly(methyl methacrylate) polycarbonate.

PubMed

Altmann, Brigitte; Steinberg, Thorsten; Giselbrecht, Stefan; Gottwald, Eric; Tomakidi, Pascal; Bächle-Haas, Maria; Kohal, Ralf-Joachim

2011-12-01

Due to the architecture of solid body tissues including bone, three-dimensional (3D) in vitro microenvironments appear favorable, since herein cell growth proceeds under more physiological conditions compared to conventional 2D systems. In the present study we show that a 3D microenvironment comprising a fibronectin-coated PMMA/PC-based micro-chip promotes differentiation of primary human osteoblasts as reflected by the densely-packed 3D bone cell aggregates and expression of biomarkers indicating osteoblast differentiation. Morphogenesis and fluorescence dye-based live/dead staining revealed homogenous cell coverage of the microcavities of the chip array, whereat cells showed high viability up to 14 days. Moreover, Azur II staining proved formation of uniform sized multilayered aggregates, exhibiting progressive intracellular deposition of extracellular bone matrix constituents comprising fibronectin, osteocalcin and osteonectin from day 7 on. Compared to 2D monolayers, osteoblasts grown in the 3D chip environment displayed differential mostly higher gene expression for osteocalcin, osteonectin, and alkaline phosphatase, while collagen type I remained fairly constant in both culture environments. Our results indicate that the 3D microenvironment, based on the PMMA biomaterial chip array promotes osteoblast differentiation, and hereby renders a promising tool for tissue-specific in vitro preconditioning of osteoblasts designated for clinically-oriented bone augmentation or regeneration. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of spaceflight and simulated weightlessness on longitudinal bone growth

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Zhang, M.; Evans, G. L.; Westerlind, K. C.; Cavolina, J. M.; Morey-Holton, E.; Turner, R. T.

2000-01-01

Indirect measurements have suggested that spaceflight impairs bone elongation in rats. To test this possibility, our laboratory measured, by the fluorochrome labeling technique, bone elongation that occurred during a spaceflight experiment. The longitudinal growth rate (LGR) in the tibia of rats in spaceflight experiments (Physiological Space Experiments 1, 3, and 4 and Physiological-Anatomical Rodent Experiment 3) and in two models of skeletal unloading (hind-limb elevation and unilateral sciatic neurotomy) were calculated. The effects of an 11 day spaceflight on gene expression of cartilage matrix proteins in rat growth plates were also determined by northern analysis and are reported for the first time in this study. Measurements of longitudinal growth indicate that skeletal unloading generally did not affect LGR, regardless of age, strain, gender, duration of unloading, or method of unloading. There was, however, one exception with 34% suppression in LGR detected in slow-growing, ovariectomized rats skeletally unloaded for 8 days by hind-limb elevation. This detection of reduced LGR by hind-limb elevation is consistent with changes in steady-state mRNA levels for type II collagen (-33%) and for aggrecan (-53%) that were detected in rats unloaded by an 11 day spaceflight. The changes detected in gene expression raise concern that spaceflight may result in changes in the composition of extracellular matrix, which could have a negative impact on conversion of growth-plate cartilage into normal cancellous bone by endochondral ossification.

Parathyroid hormone-related protein is required for tooth eruption

PubMed Central

Philbrick, William M.; Dreyer, Barbara E.; Nakchbandi, Inaam A.; Karaplis, Andrew C.

1998-01-01

Parathyroid hormone (PTH)-related protein (PTHrP)-knockout mice die at birth with a chondrodystrophic phenotype characterized by premature chondrocyte differentiation and accelerated bone formation, whereas overexpression of PTHrP in the chondrocytes of transgenic mice produces a delay in chondrocyte maturation and endochondral ossification. Replacement of PTHrP expression in the chondrocytes of PTHrP-knockout mice using a procollagen II-driven transgene results in the correction of the lethal skeletal abnormalities and generates animals that are effectively PTHrP-null in all sites other than cartilage. These rescued PTHrP-knockout mice survive to at least 6 months of age but are small in stature and display a number of developmental defects, including cranial chondrodystrophy and a failure of tooth eruption. Teeth appear to develop normally but become trapped by the surrounding bone and undergo progressive impaction. Localization of PTHrP mRNA during normal tooth development by in situ hybridization reveals increasing levels of expression in the enamel epithelium before the formation of the eruption pathway. The type I PTH/PTHrP receptor is expressed in both the adjacent dental mesenchyme and in the alveolar bone. The replacement of PTHrP expression in the enamel epithelium with a keratin 14-driven transgene corrects the defect in bone resorption and restores the normal program of tooth eruption. PTHrP therefore represents an essential signal in the formation of the eruption pathway. PMID:9751753

Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells as a Potential Source for Cartilage and Bone Regeneration: An In Vitro Study.

PubMed

Marmotti, A; Mattia, S; Castoldi, F; Barbero, A; Mangiavini, L; Bonasia, D E; Bruzzone, M; Dettoni, F; Scurati, R; Peretti, G M

2017-01-01

Umbilical cord (UC) may represent an attractive cell source for allogeneic mesenchymal stem cell (MSC) therapy. The aim of this in vitro study is to investigate the chondrogenic and osteogenic potential of UC-MSCs grown onto tridimensional scaffolds, to identify a possible clinical relevance for an allogeneic use in cartilage and bone reconstructive surgery. Chondrogenic differentiation on scaffolds was confirmed at 4 weeks by the expression of sox-9 and type II collagen; low oxygen tension improved the expression of these chondrogenic markers. A similar trend was observed in pellet culture in terms of matrix (proteoglycan) production. Osteogenic differentiation on bone-graft-substitute was also confirmed after 30 days of culture by the expression of osteocalcin and RunX-2. Cells grown in the hypertrophic medium showed at 5 weeks safranin o-positive stain and an increased CbFa1 expression, confirming the ability of these cells to undergo hypertrophy. These results suggest that the UC-MSCs isolated from minced umbilical cords may represent a valuable allogeneic cell population, which might have a potential for orthopaedic tissue engineering such as the on-demand cell delivery using chondrogenic, osteogenic, and endochondral scaffold. This study may have a clinical relevance as a future hypothetical option for allogeneic single-stage cartilage repair and bone regeneration.

Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Yuehua, E-mail: yuesjtu@126.com; Zheng, Xinfeng, E-mail: zxf272@126.com; Li, Bo, E-mail: libo@126.com

Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) andmore » bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss.« less

Evaluation of Vertical Bone Regeneration Using Block and Particulate Forms of Bio-Oss Bone Graft: A Histologic Study in the Rabbit Mandible.

PubMed

Veis, Alexander; Dabarakis, Nikolaos; Koutrogiannis, Christos; Barlas, Irodis; Petsa, Elina; Romanos, Georgios

2015-06-01

The aim of the present study was to evaluate histologically vertical bone regeneration outcomes after using bovine bone graft material in block and granular forms. The buccal bony plates of the outer mandibles of 10 New Zealand rabbits received Bio-Oss blocks that were immobilized using orthopedic mini-plates, and another 10 received granular forms that were gently packed and stabilized into the custom-made perforated metallic cubes. The mean graft area (GA), new bone area (NBA), bone-to-graft contact (BGC), and maximum vertical height reached by the new bone development (MVH) were histometrically evaluated and showed no significant differences between 2 graft types. The new bone was observed mostly close to the basal bone and developed penetrating the trabecular scaffold in the form of seams that covered the intralumen surfaces of the block type graft, while in the granular graft type the new bone was observed to grow between the graft particles usually interconnecting them. Either form of Bio-Oss was capable of providing considerable vertical bone augmentation.

Assessing a relationship between bone microstructure and growth rate: a fluorescent labelling study in the king penguin chick (Aptenodytes patagonicus).

PubMed

de Margerie, E; Robin, J-P; Verrier, D; Cubo, J; Groscolas, R; Castanet, J

2004-02-01

Microstructure-function relationships remain poorly understood in primary bone tissues. The relationship between bone growth rate and bone tissue type, although documented in some species by previous works, remains somewhat unclear and controversial. We assessed this relationship in a species with extreme adaptations, the king penguin (Aptenodytes patagonicus). These birds have a peculiar growth, interrupted 3 months after hatching by the austral winter. Before this interruption, chicks undergo extremely rapid statural and ponderal growth. We recorded experimentally (by means of fluorescent labelling) the growth rate of bone tissue in four long bones (humerus, radius, femur and tibiotarsus) of four king penguin chicks during their fastest phase of growth (3-5 weeks after hatching) and identified the associated bone tissue types ('laminar', 'longitudinal', 'reticular' or 'radial' fibro-lamellar bone tissue). We found the highest bone tissue growth rate known to date, up to 171 microm day(-1) (mean 55 microm day(-1)). There was a highly significant relationship between bone tissue type and growth rate (P<10(-6)). Highest rates were obtained with the radial microarchitecture of fibro-lamellar bone, where cavities in the woven network are aligned radially. This result supports the heuristic value of a relationship between growth rate and bone primary microstructure. However, we also found that growth rates of bone tissue types vary according to the long bone considered (P<10(-5)) (e.g. growth rates were 38% lower in the radius than in the other long bones), a result that puts some restriction on the applicability of absolute growth rate values (e.g. to fossil species). The biomechanical disadvantages of accelerated bone growth are discussed in relation to the locomotor behaviour of the chicks during their first month of life.

Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo.

PubMed

Mendes, L F; Katagiri, H; Tam, W L; Chai, Y C; Geris, L; Roberts, S J; Luyten, F P

2018-02-21

Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue intermediates (TIs) derived from human periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for stable cartilage formation in vivo using two different animal models. hPDCs were aggregated and cultured in the presence of a novel growth factor (GF) cocktail comprising of transforming growth factor (TGF)-β1, bone morphogenetic protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth factor (FGF)2. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to study in vitro differentiation. Aggregates were then implanted ectopically in nude mice and orthotopically in critical-size osteochondral defects in nude rats and evaluated by microcomputed tomography (µCT) and immunohistochemistry. Gene expression analysis after 28 days of in vitro culture revealed the expression of early and late chondrogenic markers and a significant upregulation of NOGGIN as compared to human articular chondrocytes (hACs). Histological examination revealed a bilayered structure comprising of chondrocytes at different stages of maturity. Ectopically, TIs generated both bone and mineralized cartilage at 8 weeks after implantation. Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG) production, type-II collagen, and lubricin expression. Immunostaining for human nuclei protein suggested that hPDCs contributed to both subchondral bone and articular cartilage repair. Our data indicate that in vitro derived osteochondral-like tissues can be generated from hPDCs, which are capable of producing bone and cartilage ectopically and behave orthotopically as osteochondral units.

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease

PubMed Central

Irion, Camila Iansen; Paredes, Bruno Diaz; Brasil, Guilherme Visconde; da Cunha, Sandro Torrentes; Paula, Luis Felipe; Carvalho, Alysson Roncally; de Carvalho, Antonio Carlos Campos; Carvalho, Adriana Bastos; Goldenberg, Regina Coeli dos Santos

2017-01-01

BACKGROUND Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. OBJECTIVES The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. METHODS To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. FINDINGS At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. MAIN CONCLUSIONS iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice. PMID:28767980

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease.

PubMed

Irion, Camila Iansen; Paredes, Bruno Diaz; Brasil, Guilherme Visconde; Cunha, Sandro Torrentes da; Paula, Luis Felipe; Carvalho, Alysson Roncally; Carvalho, Antonio Carlos Campos de; Carvalho, Adriana Bastos; Goldenberg, Regina Coeli Dos Santos

2017-08-01

Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice.

Changes consequent to maxillary molar distalization with the bone-anchored pendulum appliance.

PubMed

Cambiano, Aldo Otazú; Janson, Guilherme; Fuziy, Acácio; Garib, Daniela Gamba; Lorenzoni, Diego Coelho

2017-01-01

This retrospective study aimed to evaluate the dentoalveolar, skeletal, and soft tissue effects obtained with bone-anchored pendulum appliance in patients with Class II malocclusion. A total of 18 patients (4 male, 14 female) at a mean pretreatment age of 14.0 years (+1.08) were enrolled in this study. All patients were treated with the bone-anchored pendulum appliance for an average duration of 4.8 months. Only the active distalization period was evaluated with predistalization and postdistalization lateral cephalograms. Skeletal, dentoalveolar, and soft tissue variables were obtained. Based on these variables, the treatment effects were evaluated with dependent t -test. Correction of Class II molar relationship resulted from distal movement of 3.45 mm and tipping of 11.24° of the first maxillary molars. The premolars were distalized accompanying the molars. The bone-anchored pendulum appliance proved to be an effective method for distalization of maxillary molars in cases that require maximum anchorage, avoiding reciprocal mesial movement of premolars and incisors.

Classification of non-union.

PubMed

Megas, Panagiotis; Panagiotis, Megas

2005-11-01

A substantial number of experimental and clinical studies have established that the cornerstones for successful bone-healing are biomechanical stability and biological vitality of the bone, as they both provide an environment in which new bone can be formed. Non-union of long bones is a significant consequence in treating fractures. Many approaches to prevent fracture non-union have been proposed. Depending on the type and location of the non-union, treatment options include various types of bone fixation, with or without supplemental bone graft or other biophysical enhancements.

[CIP and CAP fragments of parathormone and selected parameters of calcium-phosphate balance in patients with chronic kidney disease treated with repeated haemodialysis].

PubMed

Polak-Jonkisz, Dorota; Zwolińska, Danuta; Nahaczewska, Wiesława

2010-01-01

Chronic kidney disease (CKD) leads to bone and mineral complications, which are manifested, among others, by hyperparathyroidism, calcium-phosphate and vitamin D balance disturbances. The results of investigation assessing the usefulness of CAP/CIP ratio, (cyclase activating PTH/cyclase inactive PTH) as a marker of bone turnover and bone disturbances in this group of patients are contradictory. was to estimate the concentration of CAP and CIP of parathormone, connection with selected calcium-phosphate balance parameters and usefulness of CAP/CIP ratio to differentiate bone mineral density in patients with CKD treated with repeated haemodialysis. The study included 31 children aged 5 to 18 years. Group I - 15 haemodialysed children. Group II - 16 healthy children. The patients underwent the following serum measurements: calcium concentration (Ca), inorganic phosphate (P), 1.25-dihydroxyvitamin D, parathormone (intact PTH), and CAP, CIP were evaluated with Scantibodies Laboratory Inc test. In group I the densitometric examination was done using the Lunar DPX-L system, performing the overall bone measurement. In children from group I the average values of iPTH concentration and both CIP and CAP components were significantly elevated (p<0.05) as compared to group II. CAP/CIP ratio in group I was <1; in healthy children >1. Average concentrations of Ca and 1.25(OH)2D in serum of group I were lowered, although without statistical significance in comparison with group II. CAP/CIP ratio does not differentiate the children with bone disturbances. Densitometric examination revealed osteopenic changes in 3 children and osteoporosis in 2 children. There were no statistically significant correlations between the examined parameters. 1. The CIP/CAP ratio does not differentiate the bone mineral density status and it is not associated with biochemical parameters of calcium-phosphate metabolism. 2. This indicates its poor diagnostic utility with reference to mineralization disturbances in children with chronic kidney disease.

The effect of carrier type on bone regeneration of demineralized bone matrix in vivo.

PubMed

Tavakol, Shima; Khoshzaban, Ahad; Azami, Mahmoud; Kashani, Iraj Ragerdi; Tavakol, Hani; Yazdanifar, Mahbube; Sorkhabadi, Seyed Mahdi Rezayat

2013-11-01

Demineralized bone matrix (DBM) is a bone substitute biomaterial used as an excellent grafting material. Some factors such as carrier type might affect the healing potential of this material. The background data discuss the present status of the field: Albumin as a main protein in blood and carboxymethyl cellulose (CMC) were applied frequently in the DBM gels. We investigated the bone-repairing properties of 2 DBMs with different carriers. Bone regeneration in 3 groups of rat calvaria treated with DBM from the Iranian Tissue Bank Research and Preparation Center, DBM from Hans Biomed Corporation, and an empty cavity was studied. Albumin and CMC as carriers were used. The results of bone regeneration in the samples after 1, 4, and 8 weeks of implantation were compared. The block of the histologic samples was stained with hematoxylin and eosin, and the percentage area of bone formation was calculated using the histomorphometry method. The results of in vivo tests showed a significantly stronger new regenerated bone occupation in the DBM with albumin carrier compared with the one with CMC 8 weeks after the implantation. The 2 types of DBM had a significant difference in bone regeneration. This difference is attributed to the type of carriers. Albumin could improve mineralization and bioactivity compared with CMC.

Diabetes, Biochemical Markers of Bone Turnover, Diabetes Control, and Bone

PubMed Central

Starup-Linde, Jakob

2012-01-01

Diabetes mellitus is known to have late complications including micro vascular and macro vascular disease. This review focuses on another possible area of complication regarding diabetes; bone. Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. The aim of the present review is to examine in vivo from humans on biochemical markers of bone turnover in diabetics compared to non-diabetics. Furthermore, the effect of glycemic control on bone markers and the similarities and differences of type 1- and type 2-diabetics regarding bone markers will be evaluated. A systematic literature search was conducted using PubMed, Embase, Cinahl, and SveMed+ with the search terms: “Diabetes mellitus,” “Diabetes mellitus type 1,” “Insulin dependent diabetes mellitus,” “Diabetes mellitus type 2,” “Non-insulin dependent diabetes mellitus,” “Bone,” “Bone and Bones,” “Bone diseases,” “Bone turnover,” “Hemoglobin A Glycosylated,” and “HbA1C.” After removing duplicates from this search 1,188 records were screened by title and abstract and 75 records were assessed by full text for inclusion in the review. In the end 43 records were chosen. Bone formation and resorption markers are investigated as well as bone regulating systems. T1D is found to have lower osteocalcin and CTX, while osteocalcin and tartrate-resistant acid are found to be lower in T2D, and sclerostin is increased and collagen turnover markers altered. Other bone turnover markers do not seem to be altered in T1D or T2D. A major problem is the lack of histomorphometric studies in humans linking changes in turnover markers to actual changes in bone turnover and further research is needed to strengthen this link. PMID:23482417

Prevalence of Temporal Bone Fractures in Patients with Mandibular Fractures Using Multidetector-Row CT.

PubMed

Ogura, I; Kaneda, T; Sasaki, Y; Buch, K; Sakai, O

2015-06-01

Temporal bone fracture after mandibular trauma is thought to be rare, and its prevalence has not been reported in the literature. The purpose of this study was to investigate the prevalence of temporal bone fractures in patients with mandibular fractures and the relationship between temporal bone fractures and the mandibular fracture location using multidetector-row computed tomography (MDCT). A prospective study was performed in 201 patients with mandibular fractures who underwent 64-MDCT scans. The mandibular fracture locations were classified as median, paramedian, angle, and condylar types. Statistical analysis for the relationship between prevalence of temporal bone fractures and mandibular fracture locations was performed using χ(2) test with Fisher's exact test. A P-value < 0.05 was considered statistically significant. The percentage of cases with temporal bone fracture was 3.0 % of all patients with mandibular fractures and 19.0 % of those with multiple mandibular fractures of paramedian and condylar type. There was a significant relationship between the incidence of temporal bone fracture and the paramedian- and condylar-type mandibular fracture (P = 0.001). Multiple mandibular fractures of paramedian and condylar type may be a stronger indicator for temporal bone fractures. This study suggests that patients with mandibular fracture, especially the paramedian and condylar type, should be examined for coexisting temporal bone fracture using MDCT.

Design and characterization of a composite material based on Sr(II)-loaded clay nanotubes included within a biopolymer matrix.

PubMed

Del Buffa, Stefano; Bonini, Massimo; Ridi, Francesca; Severi, Mirko; Losi, Paola; Volpi, Silvia; Al Kayal, Tamer; Soldani, Giorgio; Baglioni, Piero

2015-06-15

This paper reports on the preparation, characterization, and cytotoxicity of a hybrid nanocomposite material made of Sr(II)-loaded Halloysite nanotubes included within a biopolymer (3-polyhydroxybutyrate-co-3-hydroxyvalerate) matrix. The Sr(II)-loaded inorganic scaffold is intended to provide mechanical resistance, multi-scale porosity, and to favor the in-situ regeneration of bone tissue thanks to its biocompatibility and bioactivity. The interaction of the hybrid system with the physiological environment is mediated by the biopolymer coating, which acts as a binder, as well as a diffusional barrier to the Sr(II) release. The degradation of the polymer progressively leads to the exposure of the Sr(II)-loaded Halloysite scaffold, tuning its interaction with osteogenic cells. The in vitro biocompatibility of the composite was demonstrated by cytotoxicity tests on L929 fibroblast cells. The results indicate that this composite material could be of interest for multiple strategies in the field of bone tissue engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Osteoporosis, Fractures, and Diabetes

PubMed Central

2014-01-01

It is well established that osteoporosis and diabetes are prevalent diseases with significant associated morbidity and mortality. Patients with diabetes mellitus have an increased risk of bone fractures. In type 1 diabetes, the risk is increased by ∼6 times and is due to low bone mass. Despite increased bone mineral density (BMD), in patients with type 2 diabetes the risk is increased (which is about twice the risk in the general population) due to the inferior quality of bone. Bone fragility in type 2 diabetes, which is not reflected by bone mineral density, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers and examination methods are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. One of these methods can be trabecular bone score. The aim of the paper is to present the present state of scientific knowledge about the osteoporosis risk in diabetic patient. The review also discusses the possibility of problematic using the study conclusions in real clinical practice. PMID:25050121

Metabolic bone disease in chronic renal failure. II. Renal transplant patients.

PubMed Central

Huffer, W. E.; Kuzela, D.; Popovtzer, M. M.; Starzl, T. E.

1975-01-01

Trabecular vertebral bone of renal transplant patients was quantitatively compared with bone from normal individuals and dialyzed and nondialyzed patienets with chronic renal failure reported in detail in an earlier study. Long- and short-term transplant patients have increased bone resorption and mineralization defects similar to renal osteodystrophy in dialyzed and nondialyzed patients. However, in transplant patients the magnitude of resorption is greater, and bone volume tends to decrease rather than increase. Resorptive activity in transplant patients is maximal during the first year after transplantation. Bone volume decreases continuously for at least 96 months after transplantation. Only decreased bone volume correlated with success or failure of the renal transplant. Morphologic findings in this study correlate with other clinical and morphologic data to suggest that reduction in bone volume in transplant patients results from a combination of persistent hyperparathyroidism and suppression of bone formation by steroid therapy. Images Fig 1 PMID:1091152

[Triple fracture of the shoulder suspensory complex].

PubMed

Tamimi Mariño, I; Martin Rodríguez, I; Mora Villadeamigo, J

2013-01-01

The superior suspensory complex of the shoulder (SSCS) is a ring shaped structure composed of bones and soft tissues that play a fundamental role in the stability of the shoulder joint. Isolated injuries of the SSCS are relatively common, but injuries that affect 3 components are extremely unusual. We present a triple injury of the SSCS in a 26 year old patient with a Neer type ii clavicular fracture, a Kuhn type iii acromion fracture and an Ogawa type i coracoid fracture. An open reduction and stabilization of the clavicle was performed with 2 Kirschner nails. The acromial fracture was synthesized with 2 cannulated screws, and the coracoid fracture was treated conservatively. After 24 months of follow up the patient had an excellent functional outcome according to the Constat-Murley shoulder score and QuickDASH scoring system, and all the fractures healed correctly. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

A Comparative Analysis on Two Types of Oral Implants, Bone-Level and Tissue-Level, with Different Cantilever Lengths of Fixed Prosthesis.

PubMed

Mosavar, Alireza; Nili, Monireh; Hashemi, Sayed Raouf; Kadkhodaei, Mahmoud

2017-06-01

Depending on esthetic, anatomical, and functional aspects, in implant-prosthetic restoration of a completely edentulous jaw, the selection of implant type is highly important; however, bone- and tissue-level implants and their stress distribution in bone have not yet been comparatively investigated. Hence, finite element analysis was used to study the influence of cantilever length in a fixed prosthesis on stress distribution in peri-implant bone around these two types of oral implants. A 3D edentulous mandible was modeled. In simulations, a framework with four posterior cantilever lengths and two types of implants, bone-level and tissue-level, was considered. A compressive load was applied to the distal regions of the cantilevers, and the von-Mises stress of peri-implant bone was investigated. The independent t-test and the Pearson correlation coefficient analyzed the results (α = 0.05). Stresses in the cortical bone around the bone-level implants were greater than those in the tissue-level implants with the same cantilever length. In addition, by extending the cantilever length, the stress values in peri-implant bone increased. Therefore, when the cantilever was at its maximum length, the maximum stress was in cortical bone and around the bone-level distal implants. The results of the present study indicate that treatment with tissue-level implants is potentially more advantageous than with bone-level implants for implant-supported fixed prostheses. © 2015 by the American College of Prosthodontists.

Continuous decompression of unicameral bone cyst with cannulated screws: a comparative study.

PubMed

Brecelj, Janez; Suhodolcan, Lovro

2007-09-01

We determined the role of mechanical decompression in the resolution of unicameral bone cyst. A total of 69 children with unicameral bone cysts were treated either by (i) open curettage and bone grafting, (ii) steroid injection or (iii) cannulated screw insertion. During a mean follow-up of 69 months (range, 12-58), the cysts were evaluated by radiological criteria. The healing rates in the three groups were 25, 12 and 29% after the first treatment, and a further 50, 19 and 65% after the second. The study has demonstrated the advantages of the decompression technique for unicameral bone cysts over other treatment modalities studied.

Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect.

PubMed

Webb, Emma A; Balasubramanian, Meena; Fratzl-Zelman, Nadja; Cabral, Wayne A; Titheradge, Hannah; Alsaedi, Atif; Saraff, Vrinda; Vogt, Julie; Cole, Trevor; Stewart, Susan; Crabtree, Nicola J; Sargent, Brandi M; Gamsjaeger, Sonja; Paschalis, Eleftherios P; Roschger, Paul; Klaushofer, Klaus; Shaw, Nick J; Marini, Joan C; Högler, Wolfgang

2017-06-01

Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Clinical and bone material phenotype description and osteoblast differentiation studies. Natural history study in pediatric research centers. Eight patients with type XIV OI. Clinical examinations included bone mineral density, radiographs, echocardiography, and muscle biopsy. Bone biopsy samples (n = 3) were analyzed using histomorphometry, quantitative backscattered electron microscopy, and Raman microspectroscopy. Cellular differentiation studies were performed on proband and control osteoblasts and normal murine osteoclasts. Type XIV OI clinical phenotype ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara, and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband lumbar spine bone density z score was reduced [median -3.3 (range -4.77 to +0.1; n = 7)] and increased by +1.7 (1.17 to 3.0; n = 3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast, and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone matrix mineralization is normal and nanoporosity low. We demonstrate a complex osteoblast differentiation defect with decreased expression of early markers and increased expression of late and mineralization-related markers. Predominance of trimeric intracellular cation channel type B over type A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover. OI type XIV has a bone histology, matrix mineralization, and osteoblast differentiation pattern that is distinct from OI with collagen defects. Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities. Copyright © 2017 Endocrine Society

Molecular changes after shockwave therapy in osteoarthritic knee in rats

NASA Astrophysics Data System (ADS)

Wang, C.-J.; Sun, Y.-C.; Wu, C.-T.; Weng, L.-H.; Wang, F.-S.

2016-01-01

This study investigated the molecular changes of DKK-1, MMP13, Wnt-5a and \\upbeta -catenin after extracorporeal shockwave therapy (ESWT) in anterior cruciate ligament transected (ACLT) osteoarthritic (OA) knee in rats. 27 male Spraque-Dawley rats were divided into three groups. Group I was the control one and received sham knee arthrotomy but no ACLT or ESWT. Group II underwent ACLT, but no ESWT. Group III underwent ACLT and received ESWT. The animals were killed at 12 weeks, and the harvested knee specimens were subjected to histopathological examination and immunohistochemical analysis. Radiographs of the knees were obtained at 0 and 12 weeks. At 12 weeks, radiographs of group II showed more arthritic changes with formation of osteochondral fragments, whereas very subtle arthritis was noted in groups I and III. In histopathological examination, group II showed a significant increase of Mankin score and a decrease of subchondral bone as compared to groups I and III. Group III showed a significant decrease of Mankin score and an increase of subchondral bone, with the data comparable to group I. In immunohistochemical analysis, group II showed significant increases of DKK-1 and MMP13 and decreases of Wnt-5a and \\upbeta -catenin in articular cartilage and subchondral bone as compared to groups I and III. Group III showed significant decreases of DKK-1 and MMP13 and increases of Wnt-5a and \\upbeta -catenin, with the data comparable to group I. In conclusion, the application of ESWT causes molecular changes that are consistent with the improvement in subchondral bone remodeling and chondroprotective effect in ACLT OA knees in rats.

[In vitro differentiation of synovial-derived mesenchymal stem cells infected by adenovirus vector mediated by bone morphogenetic protein 2/7 genes into fibrocartilage cells in rabbits].

PubMed

Fu, Peiliang; Zhang, Lei; Wu, Haishan; Cong, Ruijun; Chen, Song; Ding, Zheru; Hu, Kaimen

2013-03-01

To investigate the feasibility of rabbit synovial-derived mesenchymal stem cells (SMSCs) differentiating into fibrocartilage cells by the recombinant adenovirus vector mediated by bone morphogenetic protein 2/7 (BMP-2/7) genes in vitro. SMSCs were isolated and purified from 3-month-old New Zealand white rabbits [male or female, weighing (2.1 +/- 0.3) kg]; the morphology was observed; the cells were identified with immunocytological fluorescent staining, flow cytometry, and cell cycles. The adipogenic, osteogenic, and chondrogenic differentiations were detected. The recombinant plasmid of pAdTrack-BMP-2-internal ribosome entry site (IRES)-BMP-7 was constructed and then was used to infect SMSCs. The cell DNA content and the oncogenicity were tested to determine the safety. Then infected SMSCs were cultured in incomplete chondrogenic medium in vitro. Chondrogenic differentiation of infected SMSCs was detected by RT-PCR, immunofluorescent staining, and toluidine blue staining. SMSCs expressed surface markers of stem cells, and had multi-directional potential. The transfection efficiency of SMSCs infected by recombinant plasmid of pAdTrack-BMP-2-IRES-BMP-7 was about 70%. The safety results showed that infected SMSCs had normal double time, normal chromosome number, and normal DNA content and had no oncogenicity. At 21 days after cultured in incomplete chondrocyte medium, RT-PCR results showed SMSCs had increased expressions of collegan type I and collegan type II, particularly collegan type II; the expressions of RhoA and Sox-9 increased obviously. Immunofluorescent staining and toluidine blue staining showed differentiation of SMSCs into fibrocartilage cells. It is safe to use pAdTrack-BMP-2-IRES-BMP-7 for infecting SMSCs. SMSCs infected by pAdTrack-BMP-2-IRES-BMP-7 can differentiate into fibrocartilage cells spontaneously in vitro.

Evaluating differential nuclear DNA yield rates and osteocyte numbers among human bone tissue types: A synchrotron radiation micro-CT approach.

PubMed

Andronowski, Janna M; Mundorff, Amy Z; Pratt, Isaac V; Davoren, Jon M; Cooper, David M L

2017-05-01

Molecular human identification has conventionally focused on DNA sampling from dense, weight-bearing cortical bone tissue, typically from femora or tibiae. A comparison of skeletal elements from three contemporary individuals demonstrated that elements with high quantities of cancellous bone yielded nuclear DNA at the highest rates, suggesting that preferentially sampling cortical bone may be suboptimal (Mundorff & Davoren, 2014). Despite these findings, the reason for the differential DNA yields between cortical and cancellous bone tissues remains unknown. The primary goal of this work is to ascertain whether differences in bone microstructure can be used to explain differential nuclear DNA yield among bone tissue types observed by Mundorff and Davoren (2014), with a focus on osteocytes and the three-dimensional (3D) quantification of their associated lacunae. Osteocytes and other bone cells are recognized to house DNA in bone tissue, thus examining the density of their lacunae may explain why nuclear DNA yield rates differ among bone tissue types. Lacunae were visualized and quantified using synchrotron radiation-based micro-Computed Tomographic imaging (SR micro-CT). Volumes of interest (VOIs) from cortical and cancellous bone tissues (n=129) were comparatively analyzed from the three skeletons sampled for Mundorff and Davoren's (2014) study. Analyses tested the primary hypothesis that the abundance and density of osteocytes (inferred from their lacunar spaces) vary between cortical and cancellous bone tissue types. Results demonstrated that osteocyte lacunar abundance and density vary between cortical and cancellous bone tissue types, with cortical bone VOIs containing a higher lacunar abundance and density. We found that the osteocyte lacunar density values are independent of nuclear DNA yield, suggesting an alternative explanation for the higher nuclear DNA yields from bones with greater quantities of cancellous bone tissue. The use of SR micro-CT allowed for a scale of analysis that revealed a high range of variation in lacunar abundance in both tissue types. Moreover, high-resolution SR micro-CT imaging revealed potential soft tissue remnants within marrow spaces not visible macroscopically. It is hypothesized that soft tissue remnants observed among the trabeculae of skeletal elements with high quantities of cancellous bone tissue are responsible for the high nuclear DNA yields. These findings have significant implications for bone-sample selection for nuclear DNA analysis in a forensic context when skeletal remains are recovered from the ground surface. Copyright © 2017 Elsevier B.V. All rights reserved.

[Abnormality of blood coagulation indexes in patients with de novo acute leukemia and its clinical significance].

PubMed

Xiao, Fang-Fang; Hu, Kai-Xun; Guo, Mei; Qiao, Jian-Hui; Sun, Qi-Yun; Ai, Hui-Sheng; Yu, Chang-Lin

2013-04-01

To explore hemorrhage risk and the clinical significance of abnormal change of prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (FIB), plasma thrombin time (TT) and d-dimer (D-D) in de novo acute leukemia (except for APL), the different bleeding manifestations of 114 cases of de novo acute leukemia with different coagulation indexes were analyzed retrospectively. The correlation between these blood coagulation indexes and the possible correlative clinical characteristics were analysed, including age, sex, type of acute leukemia, initial white blood cell(WBC) and platelet(Plt) count, the proportion of blast cells in bone marrow and cytogenetic abnormality of patients at diagnosis. The results indicated that the incidence of abnormal blood coagulation was as high as 78.1% for de novo AL patients. These patients with 5 normal blood coagulation indexes may have mild bleeding manifestation, but the more abnormal indexes, the more severe bleeding. Both PT and D-D were sensitive indexes for diagnosis of level II bleeding. Incidence of abnormal blood coagulation significantly correlates with the proportion of blast cells in bone marrow (χ(2) = 4.184, OR = 1.021, P < 0.05) and more with D-D (P < 0.01), while age, sex, type of AL, WBC count, Plt count and abnormality of cytogenetics did not correlate with abnormal blood coagulation. It is concluded that the coagulation and fibrinolysis are abnormal in most patients with de novo acute leukemia. More abnormal indexes indicate more severe bleeding, and both PT and D-D are sensitive indexes for diagnosis of level II bleeding. Higher proportion of blast cells in bone marrow predicts higher incidence of abnormal blood clotting. Acute leukemia with elderly age, high white blood cell count and adverse cytogenetics do not predict severer abnormal blood clotting. Detection of PT, APTT, TT, FIB, and D-D may help to judge whether the patients are in a state of hypercoagulability or disseminated intravenous coagulation, which will provide experiment evidences for early intervention and medication.

Fibrocartilage in tendons and ligaments — an adaptation to compressive load

PubMed Central

BENJAMIN, M.; RALPHS, J. R.

1998-01-01

Where tendons and ligaments are subject to compression, they are frequently fibrocartilaginous. This occurs at 2 principal sites: where tendons (and sometimes ligaments) wrap around bony or fibrous pulleys, and in the region where they attach to bone, i.e. at their entheses. Wrap-around tendons are most characteristic of the limbs and are commonly wider at their point of bony contact so that the pressure is reduced. The most fibrocartilaginous tendons are heavily loaded and permanently bent around their pulleys. There is often pronounced interweaving of collagen fibres that prevents the tendons from splaying apart under compression. The fibrocartilage can be located within fascicles, or in endo- or epitenon (where it may protect blood vessels from compression or allow fascicles to slide). Fibrocartilage cells are commonly packed with intermediate filaments which could be involved in transducing mechanical load. The ECM often contains aggrecan which allows the tendon to imbibe water and withstand compression. Type II collagen may also be present, particularly in tendons that are heavily loaded. Fibrocartilage is a dynamic tissue that disappears when the tendons are rerouted surgically and can be maintained in vitro when discs of tendon are compressed. Finite element analyses provide a good correlation between its distribution and levels of compressive stress, but at some locations fibrocartilage is a sign of pathology. Enthesis fibrocartilage is most typical of tendons or ligaments that attach to the epiphyses of long bones where it may also be accompanied by sesamoid and periosteal fibrocartilages. It is characteristic of sites where the angle of attachment changes throughout the range of joint movement and it reduces wear and tear by dissipating stress concentration at the bony interface. There is a good correlation between the distribution of fibrocartilage within an enthesis and the levels of compressive stress. The complex interlocking between calcified fibrocartilage and bone contributes to the mechanical strength of the enthesis and cartilage-like molecules (e.g. aggrecan and type II collagen) in the ECM contribute to its ability to withstand compression. Pathological changes are common and are known as enthesopathies. PMID:10029181

Odanacatib, a New Drug for the Treatment of Osteoporosis: Review of the Results in Postmenopausal Women

PubMed Central

Pérez-Castrillón, José Luis; Pinacho, Florentino; De Luis, Daniel; Lopez-Menendez, María; Dueñas Laita, Antonio

2010-01-01

Osteoclasts are specialized cells that initiate the process of bone resorption, which has two phases, dissolution of the mineral component and degradation of the organic matrix, in which cathepsin K plays a key role. Cathepsin K inhibitors, which block the activity of cathepsin on bone resorption lacunae, may be a new therapeutic option in osteoporosis. Odanacatib is a nonpeptidic biaryl inhibitor of cathepsin K. Two studies have evaluated the efficacy and safety of odanacatib, a phase I study to determine the dose and a phase II study of safety and efficacy. Due to the long half-life of odanacatib and the similar effects of different doses on bone remodeling markers, a weekly dosage was chosen for the phase II trail, with the best results being obtained with a dose of 50 mg. At 36 months, increases in bone mineral density similar to those produced by other powerful antiresorptive drugs (zoledronate and denosumab) were observed but there were differences in the behaviour of bone remodeling markers. Data on fractures from the phase III trial currently in development are required to confirm these possible advantages. PMID:20948576

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog

PubMed Central

Kawamoto, Kohei; Miyaji, Hirofumi; Nishida, Erika; Miyata, Saori; Kato, Akihito; Tateyama, Akito; Furihata, Tomokazu; Shitomi, Kanako; Iwanaga, Toshihiko; Sugaya, Tsutomu

2018-01-01

Introduction The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. Materials and methods GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. Results GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. Conclusion The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy. PMID:29713167

Bone morphogenetic protein-7 (BMP-7) augments insulin sensitivity in mice with type II diabetes mellitus by potentiating PI3K/AKT pathway.

PubMed

Chattopadhyay, Tandrika; Singh, Rajiv Ranjan; Gupta, Sarika; Surolia, Avadhesha

2017-03-01

A direct link between development of insulin resistance and the presence of chronic inflammation, in case of obesity exists, with cytokines playing an important role in glucose metabolism. Members of TGF-β superfamily, including bone morphogenetic proteins (BMPs), have been shown to be involved in islet morphogenesis, establishment of β-cell mass and adipose cell fate determination. Here, we demonstrate a novel and direct role of BMP-4 and -7 in the regulation of glucose homeostasis and insulin resistance. An age-dependent increase in serum BMP-4 and decrease in serum BMP-7 levels was observed in animal models of type II diabetes. In this study, BMP-7 and -4 have been demonstrated to have antagonistic effects on insulin signaling and thereby on glucose homeostasis. BMP-7 augmented glucose uptake in the insulin sensitive tissues such as the adipose and muscle by increasing Glut4 translocation to the plasma membrane through phosphorylation and activation of PDK1 and Akt, and phosphorylation and translocation of FoxO1 to the cytoplasm in liver/HepG2 cells. Restoration of BMP-7 levels in serum of diabetic animals resulted in decreased blood glucose levels in contrast to age matched untreated control groups, opening up a new therapeutic avenue for diabetes. On the contrary, BMP-4 inhibited insulin signaling through activation of PKC-θ isoform, and resulted in insulin resistance through the attenuation of insulin signaling. BMP-7 therefore is an attractive candidate for tackling a multifaceted disease such as diabetes, since it not only reduces body fat, but also strengthens insulin signaling, causing improved glucose uptake and ameliorating peripheral insulin resistance. © 2017 BioFactors, 43(2):195-209, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Methotrexate, combined with cyclophosphamide attenuates murine collagen induced arthritis by modulating the expression level of Breg and DCs.

PubMed

Fan, Jinnan; Luo, Jing; Yan, Caiping; Hao, Runxi; Zhao, Xiangcong; Jia, Ruihuan; He, Jiaojiao; Xu, Dan; Miao, Miao; Li, Xiaofeng

2017-10-01

To explore the mechanism of methotrexate (MTX) and its combination with cyclophosphamide (CTX) in collagen-induced arthritis (CIA), we investigated the levels of several immune cells and cytokines in mice with different treatments. CIA was induced in DBA/1 mice at the age of 7 weeks by primary immunization with 100μl emulsion containing 2mg/ml bovine type II collagen which was mixed with complete Freund's adjuvant (CFA). The booster immunization was performed with 50-100μl emulsion containing 2mg/ml bovine type II collagen (CII) mixed with incomplete Freund's adjuvant (IFA). MTX, CTX or both were administrated after the booster immunization. Therapeutic effect was evaluated by arthritic scores, X-rays and assessment of histopathological joint destruction. The expression of TNF-α, IL-6, IL-23, IL-10 were also measured. The frequencies of different immune cell subsets in the lymph node, spleen and bone marrow were determined by flow cytometry analysis. Our results showed that CTX and MTX treatment attenuated the severity of arthritis of CIA mice and reduced the levels of several cytokines. CTX and MTX treated mice showed a lower frequency of B cells in bone marrow. Also, when treated the CIA mice with MTX, alone or together with CTX, the lymph nodes and spleen exhibited a decrease in regulatory B cells (Breg) and dendritic cells (DCs). Notably, the combination of MTX and CTX had a more pronounced effect. By measuring the levels of different immune cells those participated in the development of rheumatoid arthritis (RA), our experiment may help to evaluate the therapeutic effects and prognosis of arthritic diseases. Copyright © 2017. Published by Elsevier Ltd.

Oleanolic acid acetate inhibits rheumatoid arthritis by modulating T cell immune responses and matrix-degrading enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Jin Kyeong; Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892; Kim, Sung-Wan

ABSTRACT: Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a combination of synovium joint inflammation, synovium hyperplasia, and destruction of cartilage and bone. Oleanolic acid acetate (OAA), a compound isolated from Vigna angularis, has been known to possess pharmacological activities, including anti-inflammation and anti-bone destruction. In this study, we investigated the effects of OAA on RA and the underlying mechanisms of action by using a type-II collagen-induced arthritis (CIA) mouse model and tumor necrosis factor (TNF)-α-stimulated RA synovial fibroblasts. Oral administration of OAA decreased the clinical arthritis symptoms, paw thickness, histologic and radiologic changes, and serum total andmore » anti-type II collagen IgG, IgG1, and IgG2a levels. OAA administration reduced Th1/Th17 phenotype CD4{sup +} T lymphocyte expansions and inflammatory cytokine productions in T cell activated draining lymph nodes and spleen. OAA reduced the expression and production of inflammatory mediators, such as cytokines and matrix metalloproteinase (MMP)-1/3, in the ankle joint tissue and RA synovial fibroblasts by down-regulating Akt, mitogen-activated protein kinases, and nuclear factor-κB. Our results clearly support that OAA plays a therapeutic role in RA pathogenesis by modulating helper T cell immune responses and matrix-degrading enzymes. The immunosuppressive effects of OAA were comparable to dexamethasone and ketoprofen. We provide evidences that OAA could be a potential therapeutic candidate for RA. - Highlights: • OAA attenuated chronic CIA symptoms. • OAA had a regulating effect on the T helper cell immune reaction for CIA. • The effect of OAA on the RA was comparable to the dexamethasone or ketoprofen. • OAA might be a candidate for the treatment of arthritic diseases.« less

Condyle and mandibular bone change after unilateral condylar neck fracture in growing rats.

PubMed

Hu, Y; Yang, H-f; Li, S; Chen, J-z; Luo, Y-w; Yang, C

2012-08-01

Unilateral fracture of the condylar neck in immature subjects might lead to mandible asymmetry and condyle remodelling. A rat model was used to investigate mandibular deviation and condylar remodelling associated with condyle fracture. 72 4-week-old male rats were randomly divided into three groups: an experimental group (unilateral transverse condylar fracture induced surgically), a sham operation group (surgical exposure but no fracture), and a non-operative control group (no operation). The rats were killed at intervals up to 9weeks after surgery, and outcomes were assessed using various measures of mandible deviation, histological and X-ray observation, and immunohistochemical measures of expression levels of connective tissue growth factor (CTGF) and type II collagen (Col II). The fracture led to the degeneration of mandibular size, associated with atrophy of fractured condylar process. Progressive remodelling of cartilage and increasing expression levels of CTGF and Col II were found. The authors conclude that condylar fracture can lead to asymmetries in mandible and condyle remodelling and expression of CTGF and Col II in condylar cartilage on both the ipsilateral and the contralateral sides. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A novel three-dimensional bone chip organ culture.

PubMed

Kuttenberger, Johannes; Polska, Elzbieta; Schaefer, Birgit M

2013-07-01

The objective of this study was to develop a 3D bone chip organ culture model. We aimed to collect in vitro evidence of the ability of vital bone chips to promote new bone formation. We developed a 3D in vitro hypoxic bone chip organ culture model. Histology of the bone chips was performed before and after culture and immunohistochemistry after 3-week culture. The 3D culture supernatants were tested for the presence of pro-angiogenic growth factors, TGFβ1, GADPH, bone alkaline phosphatase, osteocalcin, osteonectin, osteopontin, bone sialoprotein and collagen type I. Histology after culture revealed bone chips in a matrix of fibrin remnants and a fibrous-appearing matter. Collagen type I- and IV-positive structures were also identified. Cells could be seen on the surface of the bone chips, with spindle-shaped cells bridging the bone chip particles. Pro-angiogenic growth factors and TGFβ1were detected in the 3D cell culture supernatants. The transcripts for osteocalcin, bone sialoprotein and collagen type I were revealed only via PCR. Our results indicate that bone chips in our 3D organ culture remain vital and may stimulate the growth of a bone-forming matrix. The use of autogenous bone chips for oral and maxillofacial bone augmentation procedures is widespread in clinical practice. The rationale for this is that if bone chips remain vital in vivo, they could provide an environment promoting new bone formation through growth factors and cells. This 3D culture method is an essential tool for investigating the behaviour of bone chips.

Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency

PubMed Central

Xiong, Jinhu; Piemontese, Marilina; Thostenson, Jeff D.; Weinstein, Robert S.; Manolagas, Stavros C.; O’Brien, Charles A.

2014-01-01

Parathyroid hormone (PTH) excess stimulates bone resorption. This effect is associated with increased expression of the osteoclastogenic cytokine receptor activator of nuclear factor кB ligand (RANKL) in bone. However, several different cell types, including bone marrow stromal cells, osteocytes, and T lymphocytes, express both RANKL and the PTH receptor and it is unclear whether RANKL expression by any of these cell types is required for PTH-induced bone loss. Here we have used mice lacking the RANKL gene in osteocytes to determine whether RANKL produced by this cell type is required for the bone loss caused by secondary hyperparathyroidism induced by dietary calcium deficiency in adult mice. Thirty days of dietary calcium deficiency caused bone loss in control mice, but this effect was blunted in mice lacking RANKL in osteocytes. The increase in RANKL expression in bone and the increase in osteoclast number caused by dietary calcium deficiency were also blunted in mice lacking RANKL in osteocytes. These results demonstrate that RANKL produced by osteocytes contributes to the increased bone resorption and the bone loss caused by secondary hyperparathyroidism, strengthening the evidence that osteocytes are an important target cell for hormonal control of bone remodeling. PMID:24933342

An open cohort study of bone metastasis incidence following surgery in breast cancer patients.

PubMed

Koizumi, Mitsuru; Yoshimoto, Masataka; Kasumi, Fujio; Iwase, Takuji

2010-07-21

To help design clinical trials of adjuvant bisphosphonate therapy for breast cancer, the temporal incidence of bone metastasis was investigated in a cohort of patients. We have tried to draw the criteria to use adjuvant bisphosphonate. Consecutive breast cancer patients undergoing surgery between 1988 and 1998 (5459 patients) were followed up regarding bone metastasis until December 2006. Patients' characteristics at the time of surgery were analyzed by Cox's method, with bone metastasis as events. Patient groups were assigned according to Cox's analysis, and were judged either to require the adjuvant bisphosphonate or not, using the tentative criteria: high risk (>3% person-year), medium risk (1-3%), and low risk (<1%). Bone metastasis incidence was constant between 1.0 and 2.8% per person-year more than 10 years. Non-invasive cancer was associated with a very low incidence of bone metastasis (1/436). Multivariate Cox's analysis indicated important factors for bone metastasis were tumor grade (T), nodal grade (pN), and histology. Because T and pN were important factors for bone metastasis prediction, subgroups were made by pTNM stage. Patients at stages IIIA, IIIB and IV had an incidence of >3% per person-year, patients with stage I <1% per person-year, and those with stages II were between 1 and 3%. Further analysis with histology in stage II patients showed that stage IIB with high risk histology also had a high incidence (3% person year), whereas stage IIA with medium risk histology were <1%. Bone metastasis incidence remained constant for many years. Using pN, T, and histopathology, patients could be classified into high, medium, and low risk groups.

Long-term follow-up of callotasis lengthening of the capitate after resection of the lunate for the treatment of stage III lunate necrosis.

PubMed

Hierner, Robert; Wilhelm, Klaus

2010-04-01

The callotasis lengthening technique was used to gradually lengthen the capitate after resection of the lunate in stage IIIa necrosis in 23 patients. Results of ten patients with a follow-up of at least 5 years showed rapid and sufficient callus formation in every patient regardless of age. The callotasis lengthening modification of the Graner II operation provides all advantages and avoids the major inconvenience of the traditional Graner II operation. There was no increased rate of disturbed fracture healing. Results of the DTPA-gadolinium MRI study did not show any significant impairment of vascularization within the region of the capitate bone. With the "intrinsic bone formation," contrary to every other intercarpal arthrodesis at the wrist, there is no need for an additional bone graft.

Morphological and biomechanical analysis of a skeleton from Roman imperial necropolis of Casalecchio di Reno (Bologna, Italy, II-III c. A. D.). A possible case of crutch use.

PubMed

Belcastro, M G; Mariotti, V

2000-12-01

A Roman skeleton (T.130) from the roman necropolis of Casalecchio di Reno has been studied in order to understand if the hypothesis of crutch use, suggested by the severe articular degeneration at the hip joint that caused evident reduction of his locomotory possibilities, could be supported by the morphological alterations of other bones and joints. The pathological changes and muscular development of the upper limbs and shoulder girdle bones suggest that these parts were submitted to a great mechanical stress. The observations are consistent with the hypothesis of crutch use that would have involved a new weight-bearing function of the upper limbs in order to help locomotion, even though it is difficult to assess the number and type of the crutches. The comparison with other possible cases of crutch use reported in literature gives an additional support to the interpretation of the findings.

Altitude, pasture type, and sheep breed affect bone metabolism and serum 25-hydroxyvitamin D in grazing lambs.

PubMed

Willems, Helen; Leiber, Florian; Kohler, Martina; Kreuzer, Michael; Liesegang, Annette

2013-05-15

This study aimed to investigate the bone development of two mountain sheep breeds during natural summer grazing either in the lowlands or on different characteristic alpine pastures. Pasture types differed in topographic slope, plant species composition, general nutritional feeding value, Ca and P content, and Ca:P ratio of herbage. Twenty-seven Engadine sheep (ES) lambs and 27 Valaisian Black Nose sheep (VS) lambs were divided into four groups of 6 to 7 animals per breed and allocated to three contrasting alpine pasture types and one lowland pasture type. The lambs were slaughtered after 9 wk of experimental grazing. The steep alpine pastures in combination with a high (4.8) to very high (13.6) Ca:P ratio in the forage decreased total bone mineral content as measured in the middle of the left metatarsus of the lambs from both breeds, and cortical bone mineral content and cortical bone mineral density of ES lambs. Breed × pasture type interactions occurred in the development of total and cortical bone mineral content, and in cortical thickness, indicating that bone metabolism of different genotypes obviously profited differently from the varying conditions. An altitude effect occurred for 25-hydroxyvitamin D with notably higher serum concentrations on the three alpine sites, and a breed effect led to higher concentrations for ES than VS. Despite a high variance, there were pasture-type effects on serum markers of bone formation and resorption.

Bone Turnover Markers and Lean Mass in Pubescent Boys: Comparison Between Elite Soccer Players and Controls.

PubMed

Nebigh, Ammar; Abed, Mohamed Elfethi; Borji, Rihab; Sahli, Sonia; Sellami, Slaheddine; Tabka, Zouhair; Rebai, Haithem

2017-11-01

The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6-8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P < .001). Indeed, the total LM correlated with whole-body bone mineral density and bone mineral content (P < .001). There were significant differences within the bone formation markers and osteocalcin (formation)/C-telopeptide type I collagen (resorption) ratio between young soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P < .05) only for the young soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.

Adsorption of Hg(II) and Pb(II) ions by nanoscale zero valent iron supported on ostrich bone ash in a fixed-bed column system.

PubMed

Amiri, Mohammad Javad; Abedi-Koupai, Jahangir; Eslamian, Saeid

2017-07-01

In this research, ostrich bone ash (OBA) was modified with nanoscale zerovalent iron (nZVI) particles and applied as a novel composite adsorbent (OBA/nZVI) for dynamic adsorption/reduction of Hg(II) and Pb(II) ions in a fixed-bed column system. Entrapment of nZVI in OBA beads barricades the particles from oxidation and aggregation. The dynamic behavior of metal ions removal by OBA/nZVI was assessed as a function of inlet flow rates, bed height, initial pollutants concentration and pH. The synthesized OBA/nZVI composite was characterized by several physicochemical techniques. Increase in pH and bed height and decrease in flow rates and initial metal concentration resulted in delay of breakthrough time. OBA breakthrough profile is sharper than the OBA/nZVI breakthrough curve for both metal ions and the breakthrough times increase in the order OBA/nZVI-Hg(II) > OBA/nZVI-Pb(II) > OBA-Pb(II) > OBA-Hg(II). Based on the experiment results, redox reaction is expected to occur to a certain extent, as the standard reduction potentials of Hg(II) and Pb(II) are more than that of Fe(II). From a practical point of view, the OBA/nZVI could be applied as a material to remove Hg(II) and Pb(II) ions from natural surface and ground water with a pH value of 5-9.

Are bone turnover markers capable of predicting callus consolidation during bone healing?

PubMed

Klein, P; Bail, H J; Schell, H; Michel, R; Amthauer, H; Bragulla, H; Duda, G N

2004-07-01

The aim of this study was to determine the ability of the following bone turnover markers to monitor the course of callus consolidation during bone healing: Carboxy-terminal propeptide of procollagen type I (PICP), skeletal alkaline phosphatase (sALP), and amino-terminal propeptide of type III procollagen (PIlINP). Since interfragmentary movements have been proven to possess the ability to document the progression of bone healing in experimental studies, correlations between bone turnover markers and interfragmentary movements in vivo were investigated. Therefore, two different types of osteosyntheses representing different mechanical situations at the fracture site were compared in an ovine osteotomy model. Blood samples were taken preoperatively and postoperatively in weekly intervals over a nine-week healing period. At the same intervals, interfragmentary movements were measured in all sheep. After nine weeks, animals were sacrificed and the tibiae were evaluated both mechanically and histologically. Wide interindividual ranges were observed for all bone turnover markers. The systemic PICP level did not increase with callus consolidation. The bone-healing model seemed to influence the systemic level of PIIINP and sALP but no general correlation between bone turnover markers and interfragmentary movements could be detected. No differences between the different types of osteosyntheses and thus the different mechanical situations were observed. All analyzed markers failed as general predictors for the course of callus consolidation during bone healing.

A reliable protocol for the isolation of viable, chondrogenically differentiated human mesenchymal stem cells from high-density pellet cultures.

PubMed

Ullah, Mujib; Hamouda, Houda; Stich, Stefan; Sittinger, Michael; Ringe, Jochen

2012-12-01

Administration of chondrogenically differentiated mesenchymal stem cells (MSC) is discussed as a promising approach for the regenerative treatment of injured or diseased cartilage. The high-density pellet culture is the standard culture for chondrogenic differentiation, but cells in pellets secrete extracellular matrix (ECM) that they become entrapped in. Protocols for cell isolation from pellets often result in cell damage and dedifferentiation towards less differentiated MSC. Therefore, our aim was to develop a reliable protocol for the isolation of viable, chondrogenically differentiated MSC from high-density pellet cultures. Human bone marrow MSC were chondrogenically stimulated with transforming growth factor-β3, and the cartilaginous structure of the pellets was verified by alcian blue staining of cartilage proteoglycans, antibody staining of cartilage collagen type II, and quantitative real-time reverse-transcription polymerase chain reaction of the marker genes COL2A1 and SOX9. Trypsin and collagenases II and P were tested alone or in combination, and for different concentrations and times, to find a protocol for optimized pellet digestion. Whereas trypsin was not able to release viable cells, 90-min digestion with 300 U of collagenase II, 20 U of collagenase P, and 2 mM CaCl2 worked quite well and resulted in about 2.5×10(5) cells/pellet. The protocol was further optimized for the separation of released cells and ECM from each other. Cells were alcian blue and collagen type II positive and expressed COL2A1 and SOX9, verifying a chondrogenic character. However, they had different morphological shapes. The ECM was also uniformly alcian blue and collagen type II positive but showed different organizational and structural forms. To conclude, our protocol allows the reliable isolation of a defined number of viable, chondrogenically differentiated MSC from high-density pellet cultures. Such cells, as well as the ECM components, are of interest as research tools and for cartilage tissue engineering.

Changes in Mechanical Properties of Rat Bones under Simulated Effects of Microgravity and Radiation†

NASA Astrophysics Data System (ADS)

Walker, Azida H.; Perkins, Otis; Mehta, Rahul; Ali, Nawab; Dobretsov, Maxim; Chowdhury, Parimal

The aim of this study was to determine the changes in elasticity and lattice structure in leg bone of rats which were: 1) under Hind-Limb Suspension (HLS) by tail for 2 weeks and 2) exposed to a total radiation of 10 Grays in 10 days. The animals were sacrificed at the end of 2 weeks and the leg bones were surgically removed, cleaned and fixed with a buffered solution. The mechanical strength of the bone (elastic modulus) was determined from measurement of bending of a bone when under an applied force. Two methodologies were used: i) a 3-point bending technique and ii) classical bending where bending is accomplished keeping one end fixed. Three point bending method used a captive actuator controlled by a programmable IDEA drive. This allowed incremental steps of 0.047 mm for which the force is measured. The data is used to calculate the stress and the strain. In the second method a mirror attached to the free end of the bone allowed a reflected laser beam spot to be tracked. This provided the displacement measurement as stress levels changed. Analysis of stress vs. strain graph together with solution of Euler-Bernoulli equation for a cantilever beam allowed determination of the elastic modulus of the leg bone for (i) control samples, (ii) HLS samples and (iii) HLS samples with radiation effects. To ascertain changes in the bone lattice structure, the bones were cross-sectioned and imaged with a 20 keV beam of electrons in a Scanning Electron Microscope (SEM). A backscattered detector and a secondary electron detector in the SEM provided the images from well-defined parts of the leg bones. Elemental compositions in combination with mechanical properties (elastic modulus and lattice structure) changes indicated weakening of the bones under space-like conditions of microgravity and radiation.

Deposition of collagen type I onto skeletal endothelium reveals a new role for blood vessels in regulating bone morphology

PubMed Central

Ben Shoham, Adi; Rot, Chagai; Stern, Tomer; Krief, Sharon; Akiva, Anat; Dadosh, Tali; Sabany, Helena; Lu, Yinhui; Kadler, Karl E.

2016-01-01

Recently, blood vessels have been implicated in the morphogenesis of various organs. The vasculature is also known to be essential for endochondral bone development, yet the underlying mechanism has remained elusive. We show that a unique composition of blood vessels facilitates the role of the endothelium in bone mineralization and morphogenesis. Immunostaining and electron microscopy showed that the endothelium in developing bones lacks basement membrane, which normally isolates the blood vessel from its surroundings. Further analysis revealed the presence of collagen type I on the endothelial wall of these vessels. Because collagen type I is the main component of the osteoid, we hypothesized that the bone vasculature guides the formation of the collagenous template and consequently of the mature bone. Indeed, some of the bone vessels were found to undergo mineralization. Moreover, the vascular pattern at each embryonic stage prefigured the mineral distribution pattern observed one day later. Finally, perturbation of vascular patterning by overexpressing Vegf in osteoblasts resulted in abnormal bone morphology, supporting a role for blood vessels in bone morphogenesis. These data reveal the unique composition of the endothelium in developing bones and indicate that vascular patterning plays a role in determining bone shape by forming a template for deposition of bone matrix. PMID:27621060

Minimally invasive surgical technique: Percutaneous external fixation combined with titanium elastic nails for selective treatment of tibial fractures.

PubMed

Tu, Kai-Kai; Zhou, Xian-Ting; Tao, Zhou-Shan; Chen, Wei-Kai; Huang, Zheng-Liang; Sun, Tao; Zhou, Qiang; Yang, Lei

2015-12-01

Several techniques have been described to treat tibial fractures, which respectively remains defects. This article presents a novel intra- and extramedullary fixation technique: percutaneous external fixator combined with titanium elastic nails (EF-TENs system). The purpose of this study is to introduce this new minimally invasive surgical technique and selective treatment of tibial fractures, particularly in segmental fractures, diaphysis fractures accompanied with distal or proximal bone subfissure, or fractures with poor soft-tissue problems. Following ethical approval, thirty-two patients with tibial fractures were treated by the EF-TENs system between January 2010 and December 2012. The follow-up studies included clinical and radiographic examinations. All relevant outcomes were recorded during follow-up. All thirty-two patients were achieved follow-ups. According to the AO classification, 3 Type A, 9 Type B and 20 Type C fractures were included respectively. According to the Anderson-Gustilo classification, there were 5 Type Grade II, 3 Type Grade IIIA and 2 Type Grade IIIB. Among 32 patients, 8 of them were segmental fractures. 12 fractures accompanied with bone subfissure. Results showed no nonunion case, with an average time of 23.7 weeks (range, 14-32 weeks). Among them, there were 3/32 delayed union patients and 0/32 malunion case. 4/32 patients developed a pin track infection and no patient suffered deep infection. The external fixator was removed with a mean time of 16.7 weeks (range, 10-26 weeks). Moreover, only 1/32 patient suffered with the restricted ROM of ankle, none with the restricted ROM of knee. This preliminary study indicated that the EF-TENs system, as a novel intra- and extramedullary fixation technique, had substantial effects on selective treatment of tibial fractures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early prophylactic autogenous bone grafting in type III open tibial fractures.

PubMed

Kesemenli, Cumhur C; Kapukaya, Ahmet; Subaşi, Mehmet; Arslan, Huseyin; Necmioğlu, Serdar; Kayikçi, Cuma

2004-08-01

The authors report the results achieved in patients with type III open tibial fractures who underwent primary autogenous bone grafting at the time of debridement and skeletal stabilisation. Twenty patients with a mean age of 35.8 years (range, 24-55) were treated between 1996 and 1999. Eight fractures were type IIIA, 11 were type IIIB, and 1 was type IIIC. At the index procedure, wound debridement, external fixation and autogenous bone grafting with bone coverage were achieved. The mean follow-up period was 46 months (range, 34-55). The mean time to fixator removal was 21 weeks (range, 14-35), and the mean time to union was 28 weeks (range, 19-45). Skin coverage was achieved by a myocutaneous flap in 2 patients, late primary closure in 4, and split skin grafting in 14. One (5%) of the patients experienced delayed union, and 1 (5%) developed infection. In tibial type III open fractures, skin coverage may be delayed, using the surrounding soft tissue to cover any exposed bone after thorough débridement and wound cleansing. Primary prophylactic bone grafting performed at the same time reduces the rate of delayed union, shortens the time to union, and does not increase the infection rate.

Morphometric assessment of periodontal tissues in relation to periodontal disease in dogs.

PubMed

Kyllar, Michal; Doskarova, Barbora; Paral, Vaclav

2013-01-01

Dimensions of periodontal tissues are thought to predispose to the development of periodontal disease in man and dogs. Several studies have suggested that thin gingiva correlates with an increased incidence of periodontal disease. In this study, we hypothesized that the dimensions of periodontal tissues will vary in different breeds of dogs and could possibly correlate with the incidence of periodontal disease. Forty-two jaws of dogs aged up to 5-years were examined post-mortem and gingival and alveolar bone thickness were measured using methods of transgingival probing and digital calipers, respectively. Dogs were divided into three groups based on their body weight. Group I (< 5.0 kg; n=21), group II (5 to 10 kg; n=11), and group III (10 to 15 kg; n=10). Thickness of gingiva ranged from 0.30-mm to 3.2-mm and was relatively thinner in group I than in group II and III based on the means of ratios comparison. Alveolar bone thickness ranged from 0.27-mm to 4.1-mm and was relatively thinner in group I compared with groups II and III. Our study showed significantly thinner gingiva and alveolar bone in toy breed dogs compared with small and medium-sized breed dogs. Both gingival and alveolar bone dimensions may be predictors for severity of periodontal disease and influence clinical outcome in certain periodontal surgical procedures.

Association of Glycemic Status with Bone Turnover Markers in Type 2 Diabetes Mellitus.

PubMed

Kulkarni, Sweta Vilas; Meenatchi, Suruthi; Reeta, R; Ramesh, Ramasamy; Srinivasan, A R; Lenin, C

2017-01-01

Type 2 diabetes mellitus has profound implications on the skeleton. Even though bone mineral density is increased in type 2 diabetes mellitus patients, they are more prone for fractures. The weakening of bone tissue in type 2 diabetes mellitus can be due to uncontrolled blood sugar levels leading to high levels of bone turnover markers in blood. The aim of this study is to find the association between glycemic status and bone turnover markers in type 2 diabetes mellitus. This case-control study was carried out in a tertiary health care hospital. Fifty clinically diagnosed type 2 diabetes mellitus patients in the age group between 30 and 50 years were included as cases. Fifty age- and gender-matched healthy nondiabetics were included as controls. Patients with complications and chronic illness were excluded from the study. Depending on glycated hemoglobin (HbA1c) levels, patients were grouped into uncontrolled (HbA1c >7%, n = 36) and controlled (HbA1c <7%, n = 14) diabetics. Based on duration of diabetes, patients were grouped into newly diagnosed, 1-2 years, 3-5 years, and >5 years. Serum osteocalcin (OC), bone alkaline phosphatase (BAP), acid phosphatase (ACP), and HbA1c levels were estimated. OC/BAP and OC/ACP ratio was calculated. Student's t -test, analysis of variance, and Chi-square tests were used for analysis. Receiver operating characteristic (ROC) curve analysis was done for OC/BAP and OC/ACP ratios. Serum OC, HbA1c, and OC/BAP ratio were increased in cases when compared to controls and were statistically significant ( P < 0.001). OC/ACP ratio was decreased in type 2 diabetes mellitus and was statistically significant ( P = 0.01). In patients with >5-year duration of diabetes, HbA1c level was high and was statistically significant ( P < 0.042). BAP levels were high in uncontrolled diabetics but statistically not significant. ROC curve showed OC/BAP ratio better marker than OC/ACP ratio. Uncontrolled type 2 diabetes mellitus affects bone tissue resulting in variations in bone turnover markers. Bone turnover markers are better in predicting recent changes in bone morphology and are cost effective.