These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Lamellar Spacing in Cuboid Hydroxyapatite Scaffolds Regulates Bone Formation by Human Bone Marrow Stromal Cells  

PubMed Central

Background A major goal in bone engineering is the creation of large volume constructs (scaffolds and stem cells) that bear load. The scaffolds must satisfy two competing requirements—they need be sufficiently porous to allow nutrient flow to maintain cell viability, yet sufficiently dense to bear load. We studied the effect of scaffold macroporosity on bone formation and scaffold strength, for bone formed by human bone marrow stromal cells. Methods Rigid cubical hydroxyapatite/tricalcium phosphate scaffolds were produced by robo-casting. The ceramic line thickness was held constant, but the distance between adjacent lines was either 50, 100, 200, 500, or 1000??m. Cultured human bone marrow stromal cells were combined with the scaffolds in vitro; transplants were placed into the subcutis of immunodeficient mice. Transplants were harvested 9, 18, 23, 38, or 50 weeks later. Bone formation and scaffold strength were analyzed using histology and compression testing. Results Sixty transplants were evaluated. Cortical bone increased with transplant age, and was greatest among 500??m transplants. In contrast, maximum transplant strength was greatest among 200??m transplants. Conclusions Lamellar spacing within scaffolds regulates the extent of bone formation; 500??m yields the most new bone, whereas 200??m yields the strongest transplants. PMID:21294634

Afghani, Shahrzad; Franco, Jaime; Launey, Max; Marshall, Sally; Marshall, Grayson W.; Nissenson, Robert; Lee, Janice; Tomsia, Antoni P.; Saiz, Eduardo

2011-01-01

2

Antagonizing the ?v?3 Integrin Inhibits Angiogenesis and Impairs Woven but Not Lamellar Bone Formation Induced by Mechanical Loading  

PubMed Central

Angiogenesis and osteogenesis are critically linked, though the role of angiogenesis is not well understood in osteogenic mechanical loading. In this study, either damaging or non-damaging cyclic axial compression was used to generate woven bone formation (WBF) or lamellar bone formation (LBF), respectively, at the mid-diaphysis of the adult rat forelimb. ?v?3 integrin targeted nanoparticles or vehicle was injected intravenously following mechanical loading. ?3 integrin subunit expression on vasculature was maximal 7 days after damaging mechanical loading, but was still robustly expressed 14 days after loading. Accordingly, targeted nanoparticle delivery in WBF loaded limbs was increased compared to non-loaded limbs. Vascularity was dramatically increased after WBF loading (+700% on day 14) and modestly increased after LBF loading (+50% on day 14). This increase in vascularity was inhibited by nanoparticle treatment in both WBF and LBF loaded limbs at days 7 and 14 after loading. Decreased vascularity led to diminished woven, but not lamellar, bone formation. Decreased woven bone formation resulted in impaired structural properties of the skeletal repair, particularly in post-yield behavior. These results demonstrate that ?v?3 integrin mediated angiogenesis is critical for recovering fracture resistance following bone injury, but is not required for bone modeling after modest mechanical strain. PMID:24644077

Tomlinson, Ryan E.; Schmieder, Anne H.; Quirk, James D.; Lanza, Gregory M.; Silva, Matthew J.

2015-01-01

3

Aging diminishes lamellar and woven bone formation induced by tibial compression in adult C57BL/6.  

PubMed

Aging purportedly diminishes the ability of the skeleton to respond to mechanical loading, but recent data show that old age did not impair loading-induced accrual of bone in BALB/c mice. Here, we hypothesized that aging limits the response of the tibia to axial compression over a range of adult ages in the commonly used C57BL/6. We subjected the right tibia of old (22 month), middle-aged (12 month) and young-adult (5 month) female C57BL/6 mice to peak periosteal strains (measured near the mid-diaphysis) of -2200 ?? and -3000 ?? (n=12-15/age/strain) via axial tibial compression (4 Hz, 1200 cycles/day, 5 days/week, 2 weeks). The left tibia served as a non-loaded, contralateral control. In mice of every age, tibial compression that engendered a peak strain of -2200 ?? did not alter cortical bone volume but loading to a peak strain of -3000 ?? increased cortical bone volume due in part to woven bone formation. Both loading magnitudes increased total volume, medullary volume and periosteal bone formation parameters (MS/BS, BFR/BS) near the cortical midshaft. Compared to the increase in total volume and bone formation parameters of 5-month mice, increases were less in 12- and 22-month mice by 45-63%. Moreover, woven bone incidence was greatest in 5-month mice. Similarly, tibial loading at -3000 ?? increased trabecular BV/TV of 5-month mice by 18% (from 0.085 mm3/mm3), but trabecular BV/TV did not change in 12- or 22-month mice, perhaps due to low initial BV/TV (0.032 and 0.038 mm3/mm3, respectively). In conclusion, these data show that while young-adult C57BL/6 mice had greater periosteal bone formation following loading than middle-aged or old mice, aging did not eliminate the ability of the tibia to accrue cortical bone. PMID:24836737

Holguin, Nilsson; Brodt, Michael D; Sanchez, Michelle E; Silva, Matthew J

2014-08-01

4

Lamellar reaction phenomena: from intercalation to nanomaterials formation  

Microsoft Academic Search

Lamellar reaction processes govern the formation and properties of a wide range of materials of fundamental and technological interest, offering the potential to control the structure, composition and dimension of materials down to the nanoscale. Environmental transmission electron microscopy, complementary investigations, and atomistic modeling have been combined to explore the mechanisms that control these processes. Model transition metal disulfide (e.g.

Michael J. McKelvy; Renu Sharma; Andrew V. G. Chizmeshya

2006-01-01

5

Lamellar macular hole formation following vitrectomy for rhegmatogenous retinal detachment repair  

PubMed Central

Background The purpose of this study was to investigate lamellar macular hole formation in six patients after rhegmatogenous retinal detachment repair. Methods A retrospective review of medical records of patients who underwent primary pars plana vitrectomy for rhegmatogenous retinal detachment repair was performed. Optical coherence tomography characteristics and best-corrected visual acuity were evaluated. Patients who developed lamellar macular hole after pars plana vitrectomy for rhegmatogenous retinal detachment repair were identified. Results A total of 1185 eyes underwent pars plana vitrectomy for retinal detachment between 2004 and 2009. Optical coherence tomography evaluation was available in 450 cases. Six of these cases demonstrated lamellar macular hole formation, which was diagnosed by OCT-3. The mean time from retinal detachment surgery to lamellar hole diagnosis was 4.1 months. The presence of an epiretinal membrane on the surface of the juxtafoveal retina was a common finding in all six patients. Visual acuity was improved after successful retinal reattachment and remained unchanged after lamellar hole formation. Conclusion Lamellar macular holes developing after pars plana vitrectomy is a rare complication. Stability of optical coherence tomography findings and best-corrected visual acuity after lamellar macular hole formation may be observed for at least two years. PMID:22553416

Xirou, Tina; Kidess, Andrej; Kourentis, Christina; Xirou, Vasiliki; Feretis, Elias; Kabanarou, Stamatina A

2012-01-01

6

Holmium-YAG Laser ablation characteristics in calvarial lamellar and cortical bone: The role of water and tissue micro-architecture  

Microsoft Academic Search

The effect of tissue micro-architecture and water content on ablation rates in bone is examined. Precisely machined and prepared porcine calvarial lamellar and cortical bone were ablated with a Holmium-YAG laser (?=2.1?m). Lamellar and cortical bone differ substantially in their tissue micro-architecture. Both are porous hard tissues, which differ predominantly in size and distribution of pores within the bone matrix.

Brian Jet-Fei Wong; Vivian Sung; Michael W. Berns; Lars O. Svaasand; Joseph Neev

1995-01-01

7

Bone substitutes and bone formation  

Microsoft Academic Search

Summary  \\u000a Prompted by severe problems in autogeneic and allogeneic bone transplantation, intensive efforts were made to find sufficient\\u000a substitutes. A main demand on these materials, especially in healing of osseous defects, is to achieve results comparable\\u000a to those of auto- or allografts. These must be related to their biomechanical and particularly to their biological properties,\\u000a i. e. the ability to

H. Stützle; K. Hallfeldt; H. Mandelkow; S. Keßler; L. Schweiberer

1998-01-01

8

Assessment of lamellar level properties in mouse bone utilizing a novel spherical nanoindentation data analysis method.  

PubMed

In this work, we demonstrate the viability of using our recently developed data analysis procedures for spherical nanoindentation in conjunction with Raman spectroscopy for studying lamellar-level correlations between the local composition and local mechanical properties in mouse bone. Our methodologies allow us to convert the raw load-displacement datasets to much more meaningful indentation stress-strain curves that accurately capture the loading and unloading elastic moduli, the indentation yield points, as well as the post-yield characteristics in the tested samples. Using samples of two different inbred mouse strains, A/J and C57BL/6J (B6), we successfully demonstrate the correlations between the mechanical information obtained from spherical nanoindentation measurements to the local composition measured using Raman spectroscopy. In particular, we observe that a higher mineral-to-matrix ratio correlated well with a higher local modulus and yield strength in all samples. Thus, new bone regions exhibited lower moduli and yield strengths compared to more mature bone. The B6 mice were also found to exhibit lower modulus and yield strength values compared to the more mineralized A/J strain. PMID:22842281

Pathak, Siddhartha; Vachhani, Shraddha J; Jepsen, Karl J; Goldman, Haviva M; Kalidindi, Surya R

2012-09-01

9

Peripheral Leptin Regulates Bone Formation  

PubMed Central

Substantial evidence does not support the prevailing view that leptin, acting through a hypothalamic relay, decreases bone accrual by inhibiting bone formation. To clarify the mechanisms underlying regulation of bone architecture by leptin, we evaluated bone growth and turnover in wild type (WT) mice, leptin receptor-deficient db/db mice, leptin-deficient ob/ob mice and ob/ob mice treated with leptin. We also performed hypothalamic leptin gene therapy to determine the effect of elevated hypothalamic leptin levels on osteoblasts. Finally, to determine the effects of loss of peripheral leptin signaling on bone formation and energy metabolism, we used bone marrow (BM) from WT or db/db donor mice to reconstitute the hematopoietic and mesenchymal stem cell compartments in lethally irradiated WT recipient mice. Decreases in bone growth, osteoblast-lined bone perimeter and bone formation rate were observed in ob/ob mice and greatly increased in ob/ob mice following subcutaneous administration of leptin. Similarly, hypothalamic leptin gene therapy increased osteoblast-lined bone perimeter in ob/ob mice. In spite of normal osteoclast-lined bone perimeter, db/db mice exhibited a mild but generalized osteopetrotic-like (calcified cartilage encased by bone) skeletal phenotype and greatly reduced serum markers of bone turnover. Tracking studies and histology revealed quantitative replacement of BM cells following BM transplantation. WT mice engrafted with db/db BM did not differ in energy homeostasis from untreated WT mice or WT mice engrafted with WT BM. Bone formation in WT mice engrafted with WT BM did not differ from WT mice, whereas bone formation in WT mice engrafted with db/db cells did not differ from the low rates observed in untreated db/db mice. In summary, our results indicate that leptin, acting primarily through peripheral pathways, increases osteoblast number and activity. PMID:22887758

Turner, Russell T.; Kalra, Satya P.; Wong, Carmen P.; Philbrick, Kenneth A.; Lindenmaier, Laurence B.; Boghossian, Stephane; Iwaniec, Urszula T.

2012-01-01

10

Physiological variables affecting surface film formation by native lamellar body-like pulmonary surfactant particles.  

PubMed

Pulmonary surfactant (PS) is a surface active complex of lipids and proteins that prevents the alveolar structures from collapsing and reduces the work of breathing by lowering the surface tension at the alveolar air-liquid interface (ALI). Surfactant is synthesized by the alveolar type II (AT II) cells, and it is stored in specialized organelles, the lamellar bodies (LBs), as tightly packed lipid bilayers. Upon secretion into the alveolar lining fluid, a large fraction of these particles retain most of their packed lamellar structure, giving rise to the term lamellar body like-particles (LBPs). Due to their stability in aqueous media, freshly secreted LBPs can be harvested from AT II cell preparations. However, when LBPs get in contact with an ALI, they quickly and spontaneously adsorb into a highly organized surface film. In the present study we investigated the adsorptive capacity of LBPs at an ALI under relevant physiological parameters that characterize the alveolar environment in homeostatic or in pathological conditions. Adsorption of LBPs at an ALI is highly sensitive to pH, temperature and albumin concentration and to a relatively lesser extent to changes in osmolarity or Ca(2+) concentrations in the physiological range. Furthermore, proteolysis of LBPs significantly decreases their adsorptive capacity confirming the important role of surfactant proteins in the formation of surface active films. PMID:24582711

Hobi, Nina; Siber, Gerlinde; Bouzas, Virginia; Ravasio, Andrea; Pérez-Gil, Jesus; Haller, Thomas

2014-07-01

11

Nucleotides and nucleolipids derivatives interaction effects during multi-lamellar vesicles formation.  

PubMed

In this paper a micellar interface, constituted by the cationic surfactant CTAB, in presence of 1,2-epoxydodecane and nucleotides was used for catanionic multi-lamellar vesicles (MLVs) formation. The micellar solution of CTAB is able to disperse the 1,2 epoxydodecane in the micellar core promoting the reaction of this reagent with the nucleotide attracted by the positive surface charge of the micellar aggregates. The alkylation of AMP and UMP nucleotides leads to the synthesis of nucleolipids. The behaviour of the supramolecular structures formed depends on the starting reagents (AMP, UMP and AMP+UMP) and on the assembly capabilities of the products. In particular nucleotides and nucleotides derivatives interaction effects are evaluated during the multi-lamellar vesicles formation. NMR spectroscopy and UV-vis measurements performed on MLVs showed strong aryl interactions. Interestingly, NMR spectra revealed prevailing stacking interactions between complementary nucleolipids. The assembly of complementary nucleotides affects the course of the reaction during the MLVs formation. Moreover the MLVs supramolecular stability has been tested by means of turbidity and UV-vis measurements. In particular, an enhanced stability has been found in systems prepared with complementary nucleotides confirming that in these systems the self-assembly process is influenced by nucleolipids interactions. Furthermore by following the hypocromic effect during the micellar catalysis, we showed that even in the earlier stages of the reaction significant differences are detectable. PMID:18337067

Cuomo, Francesca; Lopez, Francesco; Angelico, Ruggero; Colafemmina, Giuseppe; Ceglie, Andrea

2008-07-15

12

Synthesis of yttria-based crystalline and lamellar nanostructures and their formation mechanism.  

PubMed

A nonaqueous synthetic route for the preparation of a regular crystalline yttria mesostructure is presented. The reaction between yttrium alkoxides and benzyl alcohol results in the formation of a highly ordered lamellar nanocomposite consisting of yttria layers with a confined thickness of about 0.6 nm, separated from each other by organic layers of intercalated benzoate molecules. Doping with europium leads to strong red luminescence. The nanostructure formation proceeds via two reactions. A C--C bond formation occurs between benzyl alcohol and the isopropanolate ligand. At the same time, yttrium oxide catalyzes two low-temperature hydride-transfer reactions to form benzoic acid and toluene from benzyl alcohol via benzaldehyde, thus limiting the growth of the thickness of the lamellae. PMID:17193361

Pinna, Nicola; Garnweitner, Georg; Beato, Pablo; Niederberger, Markus; Antonietti, Markus

2005-01-01

13

Lamellar Formation and Relaxatin in Simple Sheared Poly(ethylene terephthalate) by Small-Angle X-ray Scattering  

SciTech Connect

Semicrystalline poly(ethylene terephthalate) (PET) was oriented with an equal channel angular extrusion (ECAE) process at room temperature, which applied simple shear deformation and generated unique asymmetric lamellar texture. In-situ small-angle X-ray scattering (SAXS) measurements were utilized to study the changes of lamellar structure during heating in samples with and without experiencing the simple shear deformation. The total scattered intensity, fractions of isotropic and anisotropic scattered intensities, orientation factors, and long periods along different shear directions were determined from 2-dimensional SAXS patterns. Orientation-stable {alpha}-lamellae with their normal perpendicular to the shear plane exhibited a larger long period after shear and a rapid decrease in long period upon heating, while less orientation-stable {beta}-lamellae with their normal perpendicular to the flow direction exhibited a smaller long period after shear but only a slight decrease in long period upon heating. The thermally induced lamellar misorientaton could be attributed to the processes of lamellar relaxation and recrystallization of the amorphous phase. The possible molecular mechanisms for lamellar formation during simple shear are also discussed.

Wang,Z.; Xia, Z.; Yu, Z.; Chen, E.; Sue, H.; Han, C.; Hsiao, B.

2006-01-01

14

Influence of the mineral staggering on the elastic properties of the mineralized collagen fibril in lamellar bone.  

PubMed

In this work, a three-dimensional finite element model of the staggered distribution of the mineral within the mineralized collagen fibril has been developed to characterize the lamellar bone elastic behavior at the sub-micro length scale. Minerals have been assumed to be embedded in a collagen matrix, and different degrees of mineralization have been considered allowing the growth of platelet-shaped minerals both in the axial and the transverse directions of the fibril, through the variation of the lateral space between platelets. We provide numerical values and trends for all the elastic constants of the mineralized collagen fibril as a function of the volume fraction of mineral. In our results, we verify the high influence of the mineral overlapping on the mechanical response of the fibril and we highlight that the lateral distance between crystals is relevant to the mechanical behavior of the fibril and not only the mineral overlapping in the axial direction. PMID:25498297

Vercher-Martínez, Ana; Giner, Eugenio; Arango, Camila; Javier Fuenmayor, F

2015-02-01

15

Effects of ipriflavone on perialveolar bone formation.  

PubMed

The effect of ipriflavone (IP), a synthetic isoflavonoid derivative, on in vivo bone formation was studied in rat perialveolar bone by surgically producing a hole in the mandibular bone. The holes were filled either with powdered IP or with compounds containing no osteoinductive properties such as biostite and Htr (hard tissue replacement). In control animals, the holes were left to heal spontaneously. The animals were killed 3, 28, and 40 days after surgery and a detailed morphological and morphometric study was performed on the perialveolar bone surrounding the wounds. Three days after surgery (inflammatory phase) the bone wounds were occupied by hemorragic and inflammatory cells in both the untreated and IP-treated bone defects. Twenty-eight days after surgery, bone formation was evident with new bone spiculae particularly concentrated in the area of the bone lesion closest to the adjacent periodontal ligament. Morphometric measurements of the areas occupied by new bone showed that the synthesis of perialveolar bone was significantly stimulated by IP. The repair of the bone defects by new bone formation progressed by day 40, but only in the presence of IP were the original holes almost completely repaired. Conversely, biostite and Htr did not influence promotion of new bone formation. In conclusion, the results of the present study are consistent with a role of IP in stimulating osteogenesis and suggest that this compound could represent a potential therapeutic tool to promote repair of injured perialveolar bone. PMID:9744990

Martini, M; Formigli, L; Tonelli, P; Giannelli, M; Amunni, F; Naldi, D; Brandi, M L; Zecchi Orlandini, S; Orlandini, G E

1998-10-01

16

Bones' Adaptive Response to Mechanical Loading Is Essentially Linear Between the Low Strains Associated With Disuse and the High Strains Associated With the Lamellar/Woven Bone Transition  

PubMed Central

There is a widely held view that the relationship between mechanical loading history and adult bone mass/strength includes an adapted state or “lazy zone” where the bone mass/strength remains constant over a wide range of strain magnitudes. Evidence to support this theory is circumstantial. We investigated the possibility that the “lazy zone” is an artifact and that, across the range of normal strain experience, features of bone architecture associated with strength are linearly related in size to their strain experience. Skeletally mature female C57BL/6 mice were right sciatic neurectomized to minimize natural loading in their right tibiae. From the fifth day, these tibiae were subjected to a single period of external axial loading (40, 10-second rest interrupted cycles) on alternate days for 2 weeks, with a peak dynamic load magnitude ranging from 0 to 14 N (peak strain magnitude: 0–5000 µ?) and a constant loading rate of 500 N/s (maximum strain rate: 75,000 µ?/s). The left tibiae were used as internal controls. Multilevel regression analyses suggest no evidence of any discontinuity in the progression of the relationships between peak dynamic load and three-dimensional measures of bone mass/strength in both cortical and cancellous regions. These are essentially linear between the low-peak locomotor strains associated with disuse (?300 µ?) and the high-peak strains derived from artificial loading and associated with the lamellar/woven bone transition (?5000 µ?). The strain:response relationship and minimum effective strain are site-specific, probably related to differences in the mismatch in strain distribution between normal and artificial loading at the locations investigated. © 2012 American Society for Bone and Mineral Research. PMID:22431329

Sugiyama, Toshihiro; Meakin, Lee B; Browne, William J; Galea, Gabriel L; Price, Joanna S; Lanyon, Lance E

2012-01-01

17

Hormonal and Local Regulation of Bone Formation.  

ERIC Educational Resources Information Center

Reviews effects of hormones, systemic factors, and local regulators on bone formation. Identifies and explains the impact on bone growth of several hormones as well as the components of systemic and local systems. Concentrates on bone collagen and DNA synthesis. (Physicians may earn continuing education credit by completing an appended test). (ML)

Canalis, Ernesto

1985-01-01

18

Bones' adaptive response to mechanical loading is essentially linear between the low strains associated with disuse and the high strains associated with the lamellar/woven bone transition.  

PubMed

There is a widely held view that the relationship between mechanical loading history and adult bone mass/strength includes an adapted state or "lazy zone" where the bone mass/strength remains constant over a wide range of strain magnitudes. Evidence to support this theory is circumstantial. We investigated the possibility that the "lazy zone" is an artifact and that, across the range of normal strain experience, features of bone architecture associated with strength are linearly related in size to their strain experience. Skeletally mature female C57BL/6 mice were right sciatic neurectomized to minimize natural loading in their right tibiae. From the fifth day, these tibiae were subjected to a single period of external axial loading (40, 10-second rest interrupted cycles) on alternate days for 2 weeks, with a peak dynamic load magnitude ranging from 0 to 14?N (peak strain magnitude: 0-5000?µ?) and a constant loading rate of 500?N/s (maximum strain rate: 75,000?µ?/s). The left tibiae were used as internal controls. Multilevel regression analyses suggest no evidence of any discontinuity in the progression of the relationships between peak dynamic load and three-dimensional measures of bone mass/strength in both cortical and cancellous regions. These are essentially linear between the low-peak locomotor strains associated with disuse (?300?µ?) and the high-peak strains derived from artificial loading and associated with the lamellar/woven bone transition (?5000?µ?). The strain:response relationship and minimum effective strain are site-specific, probably related to differences in the mismatch in strain distribution between normal and artificial loading at the locations investigated. PMID:22431329

Sugiyama, Toshihiro; Meakin, Lee B; Browne, William J; Galea, Gabriel L; Price, Joanna S; Lanyon, Lance E

2012-08-01

19

Bone formation in axial spondyloarthritis.  

PubMed

The success of targeted therapies directed against tumor necrosis factor for patients with spondyloarthritis has shifted the focus of physicians and scientists towards the prevention of structural damage to the involved structures, in particular the sacroiliac joints and the spine, to avoid loss of function and disability. Structural damage to the skeleton as witnessed by radiography mainly consists of new bone formation potentially progressively leading to spine or joint ankylosis. This important long-term outcome parameter has been difficult to study, not alone because the time window for change may be long but also because human tissues with direct translational relevance are rarely available. Data from rodent models have identified growth factor signaling pathways as relevant targets. Both human and animal studies have tried to understand the link between inflammation and new bone formation. At the current moment, most evidence points towards a strong link between both but with the question still lingering about the sequence of events, disease triggers, and the interdependence of both features of disease. New discoveries such as a masterswitch T cell population that carries the IL23 receptor and the analysis of auto-antibodies directed again noggin and sclerostin are contributing to innovative insights into the pathophysiology of disease. Long-term data with tumor necrosis factor (TNF) inhibitors also suggest that some window of opportunity may exist to inhibit structural disease progression. All these data provide support for a further critical analysis of the available datasets and boost research in the field. The introduction of novel disease definitions, in particular the characterization of non-radiographic axial spondyloarthritis patients, will likely be instrumental in our further understanding of structural damage. PMID:25488783

Lories, Rik J; Haroon, Nigil

2014-10-01

20

Strontium ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys ( Macaca fascicularis)  

Microsoft Academic Search

Strontium ranelate (S12911) has previously been shown to stimulate bone formation and inhibit bone resorption in rats. To determine whether strontium ranelate affects normal bone remodeling, we studied the effect of strontium ranelate on alveolar bone in monkeys. Strontium ranelate, at dosages of 100, 275, and 750 mg\\/kg per day, or vehicle, were given by gavage to 31 normal adult

J Buehler; P Chappuis; J. L Saffar; Y Tsouderos; A Vignery

2001-01-01

21

Mechanisms of osteoclast-dependent bone formation  

PubMed Central

Should we believe that osteoclasts are only involved in bone resorption? What about their contribution to bone formation? In this article I will review evidence that bone formation can be regulated by osteoclasts. Why is this? Likely because in the physiologic condition of bone remodeling, bone resorption and formation are balanced, and there is no better way to control this equilibrium than through a concerted action between the two cell types. Although the influence of osteoblasts on osteoclastic bone resorption is well documented and consolidated over time, what osteoclasts do to regulate osteoblast activity is still matter of intense investigation. The original hypothesis that all is in the osteoblast-seeking factors stored in the bone matrix, released and activated during bone resorption, is now being challenged by several studies, suggesting that osteoclasts are also capable of producing ‘clastokines' that regulate osteoblast performance. Indeed, several of them have been demonstrated to orchestrate osteoclast–osteoblast activities. However, we are probably still at the dawn of a new era, and future work will tell us whether any of these clastokines can be exploited to stimulate bone formation and rebalance bone remodeling in skeletal diseases. PMID:24422142

Teti, Anna

2013-01-01

22

Space flight and bone formation  

NASA Technical Reports Server (NTRS)

Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

Doty, St B.

2004-01-01

23

The Kinetics of Non-Lamellar Phase Formation in DOPE-Me: Relevance to Biomembrane Fusion  

Microsoft Academic Search

The mechanism of the lamellar\\/inverted cubic ( Q II) phase transition is related to that of membrane fusion in lipid systems. N-Monomethylated dioleoylphosphatidylethanolamine (DOPE-Me) exhibits this transition and is commonly used to investigate the effects of exogenous substances, such as viral fusion peptides, on the mechanism of membrane fusion. We studied DOPE-Me phase behavior as a first step in evaluating

V. Cherezov; D. P. Siegel; W. Shaw; S. W. Burgess; M. Caffrey

2003-01-01

24

Hierarchical Formation of Fibrillar and Lamellar Self-Assemblies from Guanosine-Based Motifs  

PubMed Central

Here we investigate the supramolecular polymerizations of two lipophilic guanosine derivatives in chloroform by light scattering technique and TEM experiments. The obtained data reveal the presence of several levels of organization due to the hierarchical self-assembly of the guanosine units in ribbons that in turn aggregate in fibrillar or lamellar soft structures. The elucidation of these structures furnishes an explanation to the physical behaviour of guanosine units which display organogelator properties. PMID:20798860

Neviani, Paolo; Sarazin, Dominique; Schmutz, Marc; Blanck, Christian; Giuseppone, Nicolas; Spada, Gian Piero

2010-01-01

25

Dexamethsone suppresses bone formation via the osteoclast.  

PubMed

Glucocorticoids are central to treating inflammatory and immune disorders. These steroids, however, profoundly impact the skeleton, particularly when administered for prolonged periods. In fact, high-dose glucocorticoid therapy is almost universally associated with bone loss, prompting among the most common forms of crippling osteoporosis. Despite the frequency and severity of glucocorticoid-induced osteoporosis, its treatment is less than satisfactory, suggesting that its pathogenesis is incompletely understood. Net bone mass represents the relative activities of osteoblasts and osteoclasts and there is little question that glucocorticoids suppress the bone-forming cells, in vivo, via a process involving accelerated apoptosis (Weinstein 2001; Weinstein, Jilka, Parfitt, et al. 1998). Surprisingly, however, addition of glucocorticoids to cultures of osteoprogenitor cells actually increases their capacity to form mineralized bone nodules (Aubin 1999; Purpura, Aubin, and Zandstra 2004). This paradox raises the possibility that glucocorticoid suppression of bone formation, in vivo, reflects, at least in part, the steroid's targeting intermediary cells, which in turn inhibit the osteoblast. Bone remodeling is an ever-occuring event in mammals which is characterized by tethering of osteoclast and osteoblast function. The process is initiated by osteoclasts (OCs) resorbing a packet of bone, which in turn leads to osteoblasts being recruited to the site of resorption. This process establishes that osteoclastic bone resorption, in some manner, promotes osteoblastic bone formation at the same location. Consequently, pathologically or pharmacologically inhibited resorption eventuates in arrested osteoblast activity. PMID:17966386

Kim, Hyun-Ju; Zhao, Haibo; Kitaura, Hideki; Bhattacharyya, Sandip; Brewer, Judson A; Muglia, Louis J; Ross, F Patrick; Teitelbaum, Steven L

2007-01-01

26

Metallic materials stimulating bone formation.  

PubMed

Metallic materials implanted into bone defects are generally encapsulated by a fibrous tissue. Some metallic materials such as titanium and tantalum, however, have been revealed to bond to the living bone without forming the fibrous tissue, when they were subjected to NaOH solution and heat treatments. Thus treated metals form bone tissue around them even in muscle, when they take a porous form. This kind of osteoconductive and osteoinductive properties are attributed to sodium titanate or tantalate layer on their surfaces formed by the NaOH and heat treatments. These layers induce the deposition of bonelike apatite on the surface of the metals in the living body. This kind of bioactive metals are useful as bone substitutes even highly loaded portions, such as hip joint, spine and tooth root. PMID:15468833

Kokubo, T

2004-05-01

27

Hypothalamic Y2 receptors regulate bone formation  

PubMed Central

Neuropeptide Y (NPY) is a downstream modulator of leptin action, possibly at the level of the arcuate nucleus where NPY neurons are known to express both leptin receptors and Y2 receptors. In addition to the well-described role of NPY and leptin in energy balance and obesity, intracerebroventricular administration of NPY or leptin also causes bone loss. Here we show that Y2 receptor–deficient mice have a twofold increase in trabecular bone volume as well as greater trabecular number and thickness compared with control mice. We also demonstrate that central Y2 receptors are crucial for this process, since selective deletion of hypothalamic Y2 receptors in mature conditional Y2 knockout mice results in an identical increase in trabecular bone volume within 5 weeks. This hypothalamus-specific Y2 receptor deletion stimulates osteoblast activity and increases the rate of bone mineralization and formation, with no effect on osteoblast or osteoclast surface measurements. The lack of any changes in plasma total calcium, leptinemia, or hypothalamo-pituitary-corticotropic, -thyrotropic, -somatotropic, or -gonadotropic output suggests that Y2 receptors do not modulate bone formation by humoral mechanisms, and that alteration of autonomic function through hypothalamic Y2 receptors may play a key role in a major central regulatory circuit of bone formation. PMID:11927618

Baldock, Paul A.; Sainsbury, Amanda; Couzens, Michelle; Enriquez, Ronaldo F.; Thomas, Gethin P.; Gardiner, Edith M.; Herzog, Herbert

2002-01-01

28

Lamellar Ichthyosis with Rickets  

PubMed Central

Lamellar ichthyosis (LI) is a rare genetic disorder with autosomal recessive inheritance. It is equally seen in both sexes and usually manifests at birth. The child presents as a collodion baby. The erythema is minimal or absent; but when present, it is maximum on the face. The scaling is generalized, accentuated on lower extremities and flexural areas. Rickets is a condition in which there is softening of bones leading to fractures and deformities. It is caused by vitamin D deficiency & lack of adequate calcium in diet. Children, 6 to 24 months of age, are at a higher risk due to rapidly growing bones. The association between various types of ichthyoses and rickets is well documented. We report a case of lamellar ichthyosis with rickets in a 14-year-old girl from our part of the world. PMID:24353599

Ali, Raafia; Aman, Shahbaz; Nadeem, Muhammad

2013-01-01

29

Effects of calcium phosphate/chitosan composite on bone healing in rats: calcium phosphate induces osteon formation.  

PubMed

Vascularization of an artificial graft represents one of the most significant challenges facing the field of bone tissue engineering. Over the past decade, strategies to vascularize artificial scaffolds have been intensively evaluated using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In this work, we observed that CaP-based biomaterials implanted into rat calvarial defects showed remarkably accelerated formation and mineralization of new woven bone in defects in the initial stages, at a rate of ?60??m/day (0.8?mg/day), which was considerably higher than normal bone growth rates (several ?m/day, 0.1?mg/day) in implant-free controls of the same age. Surprisingly, we also observed histological evidence of primary osteon formation, indicated by blood vessels in early-region fibrous tissue, which was encapsulated by lamellar osteocyte structures. These were later fully replaced by compact bone, indicating complete regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only osteoinductive, but vasculogenic, and it may have contributed to the bone regeneration, despite an absence of osteons in normal rat calvaria. Further investigation will involve how this strategy can regulate formation of vascularized cortical bone such as by control of degradation rate, and use of models of long, dense bones, to more closely approximate repair of human cortical bone. PMID:24460696

Fernández, Tulio; Olave, Gilberto; Valencia, Carlos H; Arce, Sandra; Quinn, Julian M W; Thouas, George A; Chen, Qi-Zhi

2014-07-01

30

Occurrence of new bone-like tissue formation in uremic tumoral calcinosis.  

PubMed

A 55-year-old woman who had been on hemodialysis for 5years was admitted for evaluation of a hard mass in the right hip region. Her serum calcium (Ca)-phosphate (P) product was elevated. Radiographs showed periarticular calcified masses in the soft tissues around both hips and shoulders, which were characteristic of uremic tumoral calcinosis (UTC). Biopsy specimens were obtained from both right hip mass and the right iliac crest. Histological examination of hip mass revealed bone-like tissue with marrow, as well as calcified material. The bone-like tissue was categorized as heterotopic ossification (HO), because it had been formed inside soft tissue where bone-like tissue does not normally exist. Histological analysis of HO showed the formation of cancellous bone-like tissue. Woven mineralized bone-like tissue was predominant over lamellar bone-like tissue. High bone turnover combined with osteitis fibrosa-like lesion was diagnosed because of an increase of the fibrous volume, as well as clear double tetracycline labeling. Near a site of HO, numerous ALP- and Runx2-positive cuboidal osteoblast-like cells and TRAP- and cathepsin K-positive multinucleated osteoclast-like cells were noted. Histomorphometric analysis of the right iliac crest revealed osteitis fibrosa. This is the first report of HO in a patient with UTC. After parathyroidectomy, the patient's Ca-P imbalance was corrected and UTC subsided. Although the mechanism by which new bone-like tissue formation arises in the soft tissues has not yet been determined, secondary hyperparathyroidism may have contributed to the progression of UTC in this patient. PMID:23142362

Hiramatsu, Rikako; Ubara, Yoshifumi; Hayami, Noriko; Yamanouchi, Masayuki; Hasegawa, Eiko; Sumida, Keiichi; Suwabe, Tatsuya; Hoshino, Junichi; Sawa, Naoki; Amizuka, Norio; Takaichi, Kenmei

2013-02-01

31

Effects of in vitro chondrogenic priming time of bone-marrow-derived mesenchymal stromal cells on in vivo endochondral bone formation.  

PubMed

Recapitulation of endochondral ossification leads to a new concept of bone tissue engineering via a cartilage intermediate as an osteoinductive template. In this study, we aimed to investigate the influence of in vitro chondrogenic priming time for the creation of cartilage template on the in vivo endochondral bone formation both qualitatively and quantitatively. To this end, rat bone-marrow-derived mesenchymal stromal cells (MSCs) were seeded onto two scaffolds with distinguished features: a fibrous poly(lactic-co-glycolic acid)/poly(?-caprolactone) electrospun scaffold (PLGA/PCL) and a porous hydroxyapatite/tricalcium phosphate composite (HA/TCP). The constructs were then chondrogenically differentiated for 2, 3 and 4weeks in vitro, followed by subcutaneous implantation in vivo for up to 8weeks. A longer chondrogenic priming time resulted in a significantly increased amount and homogeneous deposition of the cartilage matrix on both the PLGA/PCL and HA/TCP scaffolds in vitro. In vivo, all implanted constructs gave rise to endochondral bone formation, whereas the bone volume was not affected by the length of priming time. An unpolarized woven bone-like structure, with significant amounts of cartilage remaining, was generated in fibrous PLGA/PCL scaffolds, while porous HA/TCP scaffolds supported progressive lamellar-like bone formation with mature bone marrow development. These data suggest that, by utilizing a chondrogenically differentiated MSC-scaffold construct as cartilage template, 2weeks of in vitro priming time is sufficient to generate a substantial amount of vascularized endochondral bone in vivo. The structure of the bone depends on the chemical and structural cues provided by the scaffold design. PMID:25463490

Yang, Wanxun; Both, Sanne K; van Osch, Gerjo J V M; Wang, Yining; Jansen, John A; Yang, Fang

2015-02-01

32

576. Hypoxic Adipocytes Support Early Heterotopic Bone Formation  

Microsoft Academic Search

The factors contributing to heterotopic ossification, the formation of bone in abnormal soft-tissue locations, are beginning to emerge, but very little is known about the microenvironmental conditions that promote this often devastating disease. Using a murine model in which endochondral bone formation is triggered in muscle by bone morphogenetic protein 2 (BMP2), we studied the cellular and biochemical changes near

Elizabeth A. Olmsted-Davis; Francis H. Gannon; Zbigniew Gugala; John A. Hipp; Christine Foultier-Dilling; Michael H. Heggeness; Alan R. Davis

2006-01-01

33

Uranium inhibits bone formation in physiologic alveolar bone modeling and remodeling  

SciTech Connect

The toxic effect of uranium (U) on bone modeling and remodeling was studied by performing histomorphometric measurements in the periodontal cortical bone of rats. Two different single intraperitoneal doses of uranyl nitrate (238U) were administered to two sets of rats respectively (2 and 0.8 mg/kg body wt). Rats treated with the first dose were killed 14 days postinjection (PI) and those treated with the second were killed 14, 30, and 60 days PI. The results revealed a decrease in bone formation in rats treated with uranium. On the remodeling side the decrease in bone formation was coupled to an increase in bone resorption on the 14th day PI. On the modeling side no bone resorption was observed and the decrease in bone formation was linked to an increase in resting bone zones. Bone formation depression as a key event in U intoxication is stressed.

Ubios, A.M.; Guglielmotti, M.B.; Steimetz, T.; Cabrini, R.L. (Univ. of Buenos Aires (Argentina))

1991-02-01

34

In situ micropillar compression reveals superior strength and ductility but an absence of damage in lamellar bone.  

PubMed

Ageing societies suffer from an increasing incidence of bone fractures. Bone strength depends on the amount of mineral measured by clinical densitometry, but also on the micromechanical properties of the hierarchical organization of bone. Here, we investigate the mechanical response under monotonic and cyclic compression of both single osteonal lamellae and macroscopic samples containing numerous osteons. Micropillar compression tests in a scanning electron microscope, microindentation and macroscopic compression tests were performed on dry ovine bone to identify the elastic modulus, yield stress, plastic deformation, damage accumulation and failure mechanisms. We found that isolated lamellae exhibit a plastic behaviour, with higher yield stress and ductility but no damage. In agreement with a proposed rheological model, these experiments illustrate a transition from a ductile mechanical behaviour of bone at the microscale to a quasi-brittle response driven by the growth of cracks along interfaces or in the vicinity of pores at the macroscale. PMID:24907926

Schwiedrzik, Jakob; Raghavan, Rejin; Bürki, Alexander; LeNader, Victor; Wolfram, Uwe; Michler, Johann; Zysset, Philippe

2014-07-01

35

In situ micropillar compression reveals superior strength and ductility but an absence of damage in lamellar bone  

NASA Astrophysics Data System (ADS)

Ageing societies suffer from an increasing incidence of bone fractures. Bone strength depends on the amount of mineral measured by clinical densitometry, but also on the micromechanical properties of the hierarchical organization of bone. Here, we investigate the mechanical response under monotonic and cyclic compression of both single osteonal lamellae and macroscopic samples containing numerous osteons. Micropillar compression tests in a scanning electron microscope, microindentation and macroscopic compression tests were performed on dry ovine bone to identify the elastic modulus, yield stress, plastic deformation, damage accumulation and failure mechanisms. We found that isolated lamellae exhibit a plastic behaviour, with higher yield stress and ductility but no damage. In agreement with a proposed rheological model, these experiments illustrate a transition from a ductile mechanical behaviour of bone at the microscale to a quasi-brittle response driven by the growth of cracks along interfaces or in the vicinity of pores at the macroscale.

Schwiedrzik, Jakob; Raghavan, Rejin; Bürki, Alexander; Lenader, Victor; Wolfram, Uwe; Michler, Johann; Zysset, Philippe

2014-07-01

36

Load-bearing in cortical bone microstructure: Selective stiffening and heterogeneous strain distribution at the lamellar level.  

PubMed

An improved understanding of bone mechanics is vital in the development of evaluation strategies for patients at risk of bone fracture. The current evaluation approach based on bone mineral density (BMD) measurements lacks sensitivity, and it has become clear that as well as bone mass, bone quality should also be evaluated. The latter includes, among other parameters, the bone matrix material properties, which in turn depend on the hierarchical structural features that make up bone as well as their composition. Optimal load transfer, energy dissipation and toughening mechanisms have, to some extent, been uncovered in bone. Yet, the origin of these properties and their dependence upon the hierarchical structure and composition of bone are largely unknown. Here we investigate load transfer in the osteonal and sub-osteonal levels and the mechanical behaviour of osteonal lamellae and interlamellar areas during loading. Using cantilever-based nanoindentation, in situ microtensile testing during atomic force microscopy (AFM) and digital image correlation (DIC), we report evidence for a previously unknown mechanism. This mechanism transfers load and movement in a manner analogous to the engineered "elastomeric bearing pads" used in large engineering structures. ?-RAMAN microscopy investigations showed compositional differences between lamellae and interlamellar areas. The latter have lower collagen content but an increased concentration of noncollagenous proteins (NCPs). Hence, NC-enriched areas on the microscale might be similarly important for bone failure as ones on the nanoscale. Finally, we managed to capture stable crack propagation within the interlamellar areas in a time-lapsed fashion, proving their significant contribution towards fracture toughness. PMID:23131790

Katsamenis, Orestis L; Chong, Harold M H; Andriotis, Orestis G; Thurner, Philipp J

2013-01-01

37

The hydration and ordering of lamellar block copolymer films prior to the formation of polymer vesicles  

NASA Astrophysics Data System (ADS)

Polymersomes -- vesicles based on self-assembled bilayers in turn composed of amphiphilic copolymers -- are good candidates for molecular delivery systems; hydrophilic molecules can be enclosed within the aqueous core, to be released by a trigger, which disrupts the vesicle's wall. The key to the use of these polymer vesicles as effective molecular delivery system is in the ability to efficiently encapsulate a molecular payload within the vesicle. To understand the formation mechanism of polymer vesicles via the thin film rehydration method, we have evaluated the hydration and ordering of PEO-PBO diblock copolymer thin films in a controlled water vapor atmosphere. We have performed Neutron Reflectivity, Ellipsometry and Atomic Force Microscopy measurements during the hydration process. These results show that the film swells slowly in the initial stage. It then swells rapidly at a certain critical point and makes ordered structure at the same time. The lamellae are gradually oriented parallel to the substrate with increasing water absorption.

Kamata, Yohei; Parnell, Andrew; Dennison, Andrew; Barker, Robert; Gutfreund, Philipp; Skoda, Maximilian; Mai, Shaomin; Jones, Richard

2012-02-01

38

Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function  

Microsoft Academic Search

Surface reactivity is one of the common characteristics of bone bioactive ceramics. It contributes to their bone bonding ability and their enhancing effect on bone tissue formation. During implantation, reactions occur at the material–tissue interface that lead to time-dependent changes in the surface characteristics of the implant material and the tissues at the interface. This review describes some of the

P Ducheyne; Q Qiu

1999-01-01

39

The impact of skeletal unloading on bone formation  

NASA Technical Reports Server (NTRS)

Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During space flight bone is lost principally from the bones most loaded in the 1 g environment. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. It seems likely that matrix/cell interactions will underlie much of the mechanocoupling. Integrins are a prime mediator of such interactions. The role for systemic hormones such as PTH, GH and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs and TGF beta in modulating the cellular response to load remains unclear. Our studies demonstrate that skeletal unloading leads to resistance to the anabolic actions of IGF-I on bone as a result of failure of IGF-I to activate its own signaling pathways. This is associated with a reduction in integrin expression, suggesting crosstalk between these two pathways. As the mechanism(s) by which bone responds to changes in mechanical load with changes in bone formation is further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, and that such understanding will lead to effective treatment for disuse osteoporosis in addition to preventive measures for the bone loss that accompanies space travel.

Bikle, Daniel D.; Sakata, Takeshi; Halloran, Bernard P.

2003-01-01

40

Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus  

Microsoft Academic Search

Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to

Seth W. Donahue; Michael R. Vaughan; Laurence M. Demers; Henry J. Donahue

2003-01-01

41

In Vitro and In Vivo effects of ipriflavone on bone formation and bone biomechanics  

Microsoft Academic Search

Ipriflavone (IP) positively affects bone density in postmenopausal osteoporosis, primarily by inhibiting bone resorption.\\u000a Using in vitro models of human osteoblast differentiation, we have observed that IP and some of its metabolites stimulate the expression\\u000a of bone sialoprotein, decorin, and type I collagen, and facilitate the deposition of mineralized matrix. This suggests that\\u000a IP may stimulate bone formation in addition

R. Civitelli

1997-01-01

42

Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.  

PubMed

Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover. PMID:24126694

Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

2014-09-01

43

A Novel Chitosan-?PGA Polyelectrolyte Complex Hydrogel Promotes Early New Bone Formation in the Alveolar Socket Following Tooth Extraction  

PubMed Central

A novel chitosan-?PGA polyelectrolyte complex hydrogel (C-PGA) has been developed and proven to be an effective dressing for wound healing. The purpose of this study was to evaluate if C-PGA could promote new bone formation in the alveolar socket following tooth extraction. An animal model was proposed using radiography and histomorphology simultaneously to analyze the symmetrical sections of Wistar rats. The upper incisors of Wistar rats were extracted and the extraction sockets were randomly treated with gelatin sponge, neat chitosan, C-PGA, or received no treatment. The extraction sockets of selected rats from each group were evaluated at 1, 2, 4, or 6 wk post-extraction. The results of radiography and histopathology indicated that the extraction sockets treated with C-PGA exhibited lamellar bone formation (6.5%) as early as 2 wk after the extraction was performed. Moreover, the degree of new bone formation was significantly higher (P < 0.05) in the extraction sockets treated with C-PGA at 6 wk post-extraction than that in the other study groups. In this study, we demonstrated that the proposed animal model involving symmetrical sections and simultaneous radiography and histomorphology evaluation is feasible. We also conclude that the novel C-PGA has great potential for new bone formation in the alveolar socket following tooth extraction. PMID:24658174

Chang, Hao-Hueng; Wang, Yin-Lin; Chiang, Yu-Chih; Chen, Yen-Liang; Chuang, Yu-Horng; Tsai, Shang-Jye; Heish, Kuo-Huang; Lin, Feng-Huei; Lin, Chun-Pin

2014-01-01

44

Brief Review of Models of Ectopic Bone Formation  

PubMed Central

Ectopic bone formation is a unique biologic entity—distinct from other areas of skeletal biology. Animal research models of ectopic bone formation most often employ rodent models and have unique advantages over orthotopic (bone) environments, including a relative lack of bone cytokine stimulation and cell-to-cell interaction with endogenous (host) bone-forming cells. This allows for relatively controlled in vivo experimental bone formation. A wide variety of ectopic locations have been used for experimentation, including subcutaneous, intramuscular, and kidney capsule transplantation. The method, benefits and detractions of each method are summarized in the following review. Briefly, subcutaneous implantation is the simplest method. However, the most pertinent concern is the relative paucity of bone formation in comparison to other models. Intramuscular implantation is also widely used and relatively simple, however intramuscular implants are exposed to skeletal muscle satellite progenitor cells. Thus, distinguishing host from donor osteogenesis becomes challenging without cell-tracking studies. The kidney capsule (perirenal or renal capsule) method is less widely used and more technically challenging. It allows for supraphysiologic blood and nutrient resource, promoting robust bone growth. In summary, ectopic bone models are extremely useful in the evaluation of bone-forming stem cells, new osteoinductive biomaterials, and growth factors; an appropriate choice of model, however, will greatly increase experimental success. PMID:22085228

Scott, Michelle A.; Levi, Benjamin; Askarinam, Asal; Nguyen, Alan; Rackohn, Todd; Ting, Kang; Soo, Chia

2012-01-01

45

Leptin regulates bone formation via the sympathetic nervous system  

NASA Technical Reports Server (NTRS)

We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

2002-01-01

46

Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats  

SciTech Connect

During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered)) . Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research Highlights: > 3-Day imatinib treatment. > Causes growth plate anomalies in young rats. > Causes biomechanical changes and significant bone loss at distal trabecular bone. > Results in loss of osteoclasts at osteochondral junction.

Nurmio, Mirja, E-mail: Mirja.Nurmio@utu.fi [Department of Physiology, University of Turku (Finland); Department of Pediatrics, University of Turku (Finland); Joki, Henna, E-mail: Henna.Joki@utu.fi [Department of Cell Biology and Anatomy, University of Turku (Finland); Kallio, Jenny, E-mail: Jenny.Kallio@utu.fi [Department of Physiology, University of Turku (Finland); Maeaettae, Jorma A., E-mail: jorma.maatta@utu.fi [Department of Cell Biology and Anatomy, University of Turku (Finland); Department of Turku Center for Disease Modeling, University of Turku (Finland); Vaeaenaenen, H. Kalervo, E-mail: kalervo.vaananen@utu.fi [Department of Cell Biology and Anatomy, University of Turku (Finland); Toppari, Jorma, E-mail: Jorma.Toppari@utu.fi [Department of Physiology, University of Turku (Finland); Department of Pediatrics, University of Turku (Finland); Jahnukainen, Kirsi, E-mail: Kirsi.Jahnukainen@utu.fi [Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institutet and University Hospital, Stockholm (Sweden); Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, Helsinki (Finland); Laitala-Leinonen, Tiina, E-mail: tilale@utu.fi [Department of Cell Biology and Anatomy, University of Turku (Finland)

2011-08-01

47

Phase-field modeling of the formation of lamellar nanostructures in diblock copolymer thin films under inplanar electric fields  

Microsoft Academic Search

Recent experiments show that external inplanar electric field can be employed to guide the molecular self-assembly in diblock copolymer (BCP) thin films to form lamellar nanostructures with potential applications in nanotechnology. We study this self-assembly process through a detailed coarse-grained phase-separation modeling. During the process, the free energy of the BCP films is modeled as the Ginzburg-Landau free energy with

Xiang-Fa Wu; Yuris A. Dzenis

2008-01-01

48

Demineralized Bone Matrix: Maximizing New Bone Formation for Successful Bone Implantation  

Microsoft Academic Search

\\u000a The bone scaffold formed by ground cortical bone and cancel-lous chips creates the favorable environment required for bone-forming\\u000a cells to be able to generate new bone; this property is called osteoconductivity. The demineralization of bone matrix exposes bone morphogenetic proteins (BMPs) and other bone growth promoting factors.\\u000a Because of this, deminer-alized bone matrix (DBM) not only provides a scaffold for

Lloyd Wolfinbarger Jr; Liisa M. Eisenlohr; Katrina Ruth

49

[Processing of ceramiclike xenogeneic bone and experimental study of its bone formation from composite graft combined with bone marrow].  

PubMed

Ceramiclike xenogeneic bone (CXB) was obtained from the fresh bone of pig ribs being treated by physical and chemical methods to deprive of its organic substance. The CXB possessed the same natural porous network system as that of the human. The CXB was cultured with the bone marrow stromal cells of rabit. When the marrow cells had integrated with the CXB, thus a new material was obtained. (CXB-BM), and was implanted sacro-spinal muscle of rabbit. The specimens were observed under phase microscope, light microscope and electronic scanning microscope. The results showed that: at the 2nd week after the implantation of CBX-BM composite material there began the new bone formation, and the rate of bone formation was increased with time. There was evident new bone formation after 24 weeks. The process of the new bone formation were quite similar to the composite graft of HAP red autogenous and marrow, but the former degraded faster and formed typical cancellous structure earlier. There was no new bone formation when CXB was implanted alone in the control. Both the mechanism of osteogenetic potential and its clinical application were discussed. PMID:10374603

Li, Y; Zeng, C; Wang, H

1998-03-01

50

High-intensity pulsed laser irradiation accelerates bone formation in metaphyseal trabecular bone in rat femur  

Microsoft Academic Search

.  ?Low-energy laser irradiation has positive effects on bone fracture healing, osteoblast proliferation, bone nodule formation,\\u000a and alkaline phosphatase activity. However, the mechanism by which low-energy laser irradiation affects bone is not clearly\\u000a known. It was recently found that light at a low radiation dosage is absorbed by intracellular chromophores. High-intensity\\u000a pulsed laser irradiation can produce acoustic waves in the target

Tadashi Ninomiya; Yuuichi Miyamoto; Taku Ito; Atsushi Yamashita; Masayoshi Wakita; Tsuyoshi Nishisaka

2003-01-01

51

Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption.  

PubMed

The steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and intestine where they function as xenobiotic sensors. In addition to its role as a xenobiotic sensor, previous studies in our laboratories and elsewhere have identified a role for SXR/PXR as a mediator of bone homeostasis. Here, we report that systemic deletion of PXR results in marked osteopenia with mechanical fragility in female mice as young as 4 months old. Bone mineral density (BMD) of PXR knockout (PXRKO) mice was significantly decreased compared with the BMD of wild-type (WT) mice. Micro-computed tomography analysis of femoral trabecular bones revealed that the three-dimensional bone volume fraction of PXRKO mice was markedly reduced compared with that of WT mice. Histomorphometrical analysis of the trabecular bones in the proximal tibia showed a remarkable reduction in bone mass in PXRKO mice. As for bone turnover of the trabecular bones, bone formation is reduced, whereas bone resorption is enhanced in PXRKO mice. Histomorphometrical analysis of femoral cortical bones revealed a larger cortical area in WT mice than that in PXRKO mice. WT mice had a thicker cortical width than PXRKO mice. Three-point bending test revealed that these morphological phenotypes actually caused mechanical fragility. Lastly, serum levels of phosphate, calcium, and alkaline phosphatase were unchanged in PXRKO mice compared with WT. Consistent with our previous results, we conclude that SXR/PXR promotes bone formation and suppresses bone resorption thus cementing a role for SXR/PXR as a key regulator of bone homeostasis. PMID:20876238

Azuma, Kotaro; Casey, Stephanie C; Ito, Masako; Urano, Tomohiko; Horie, Kuniko; Ouchi, Yasuyoshi; Kirchner, Séverine; Blumberg, Bruce; Inoue, Satoshi

2010-12-01

52

Rethinking the nature of fibrolamellar bone: an integrative biological revision of sauropod plexiform bone formation.  

PubMed

We present novel findings on sauropod bone histology that cast doubt on general palaeohistological concepts concerning the true nature of woven bone in primary cortical bone and its role in the rapid growth and giant body sizes of sauropod dinosaurs. By preparing and investigating longitudinal thin sections of sauropod long bones, of which transverse thin sections were published previously, we found that the amount of woven bone in the primary complex has been largely overestimated. Using comparative cellular and light-extinction characteristics in the two section planes, we revealed that the majority of the bony lamina consists of longitudinally organized primary bone, whereas woven bone is usually represented only by a layer a few cells thin in the laminae. Previous arguments on sauropod biology, which have been based on the overestimated amount, misinterpreted formation process and misjudged role of woven bone in the plexiform bone formation of sauropod dinosaurs, are thereby rejected. To explain the observed pattern in fossil bones, we review the most recent advances in bone biology concerning bone formation processes at the cellular and tissue levels. Differentiation between static and dynamic osteogenesis (SO and DO) and the revealed characteristics of SO- versus DO-derived bone tissues shed light on several questions raised by our palaeohistological results and permit identification of these bone tissues in fossils with high confidence. By presenting the methods generally used for investigating fossil bones, we show that the major cause of overestimation of the amount of woven bone in previous palaeohistological studies is the almost exclusive usage of transverse sections. In these sections, cells and crystallites of the longitudinally organized primary bone are cut transversely, thus cells appear rounded and crystallites remain dark under crossed plane polarizers, thereby giving the false impression of woven bone. In order to avoid further confusion in palaeohistological studies, we introduce new osteohistological terms as well as revise widely used but incorrect terminology. To infer the role of woven bone in the bone formation of fast-growing tetrapods, we review some aspects of the interrelationships between the vascularity of bone tissues, basal metabolic rate, body size and growth rate. By putting our findings into the context of osteogenesis, we provide a new model for the diametrical limb bone growth of sauropods and present new implications for the evolution of fast growth in vertebrates. Since biomechanical studies of bone tissues suggest that predominant collagen fibre orientation (CFO) is controlled by endogenous, functional and perhaps phylogenetic factors, the relationship between CFO and bone growth rate as defined by Amprino's rule, which has been the basis for the biological interpretation of several osteohistological features, must be revised. Our findings draw attention to the urgent need for revising widely accepted basic concepts of palaeohistological studies, and for a more integrative approach to bone formation, biomechanics and bone microstructural features of extant and extinct vertebrates to infer life history traits of long extinct, iconic animals like dinosaurs. PMID:23647662

Stein, Koen; Prondvai, Edina

2014-02-01

53

Deep anterior lamellar Keratoplasty.  

PubMed

Keratoconus is a disease causing increased steepening of the cornea resulted in irregular astigmatism. Treatment options are Glasses, Hard contact lenses, Cross linking, Intracorneal Segments insertion, Refractive surgery (Gilda et al., 2008), or Keratoplasty. Lamellar Keratoplasty (LKP) can be a better choice to manage cases of moderate and some cases of severe Keratoconus without deep scarring and severe thinning, also in cases of corneal scarring not involving the deeper layers of the cornea. LKP is a corneal graft technique consisting of transplantation of partial-thickness donor tissue, devoid of endothelium, Descemet membrane (DM), and rear stroma into a recipient healthy stromal bed after dissection of pathologic anterior stroma. However, deep lamellar Keratoplasty (DLKP) is a surgical method that completely removes pathologic corneal stroma tissue down to the DM, followed by transplantation of donor cornea without endothelium over the host bed. DLKP has a number of advantages over penetrating Keratoplasty (PKP). Because it does not violate the intraocular structures of the eye, it diminishes or eliminates the chance of postoperative glaucoma, cataract formation, retinal detachment, cystoids macular edema, expulsive choroidal hemorrhage and epithelial ingrowths. Furthermore, this procedure avoids the replacement of host endothelium with donor endothelium and thus precludes endothelial graft rejection, with comparable visual outcomes and low rate of chronic endothelial cell loss compared to PKP. PMID:23960861

Al-Kharashi, Soliman A; Al-Obailan, Majed M; Almohaimeed, Mansour; Al-Torbak, Abdullah A

2009-10-01

54

Deep anterior lamellar Keratoplasty  

PubMed Central

Keratoconus is a disease causing increased steepening of the cornea resulted in irregular astigmatism. Treatment options are Glasses, Hard contact lenses, Cross linking, Intracorneal Segments insertion, Refractive surgery (Gilda et al., 2008), or Keratoplasty. Lamellar Keratoplasty (LKP) can be a better choice to manage cases of moderate and some cases of severe Keratoconus without deep scarring and severe thinning, also in cases of corneal scarring not involving the deeper layers of the cornea. LKP is a corneal graft technique consisting of transplantation of partial-thickness donor tissue, devoid of endothelium, Descemet membrane (DM), and rear stroma into a recipient healthy stromal bed after dissection of pathologic anterior stroma. However, deep lamellar Keratoplasty (DLKP) is a surgical method that completely removes pathologic corneal stroma tissue down to the DM, followed by transplantation of donor cornea without endothelium over the host bed. DLKP has a number of advantages over penetrating Keratoplasty (PKP). Because it does not violate the intraocular structures of the eye, it diminishes or eliminates the chance of postoperative glaucoma, cataract formation, retinal detachment, cystoids macular edema, expulsive choroidal hemorrhage and epithelial ingrowths. Furthermore, this procedure avoids the replacement of host endothelium with donor endothelium and thus precludes endothelial graft rejection, with comparable visual outcomes and low rate of chronic endothelial cell loss compared to PKP. PMID:23960861

Al-Kharashi, Soliman A.; Al-Obailan, Majed M.; Almohaimeed, Mansour; Al-Torbak, Abdullah A.

2009-01-01

55

Overexpressing Sonic Hedgehog Peptide Restores Periosteal Bone Formation in a Murine Bone Allograft Transplantation Model  

PubMed Central

Although activation of hedgehog (Hh) signaling has been shown to induce osteogenic differentiation in vitro and bone formation in vivo, the underlying mechanisms and the potential use of Hh-activated mesenchymal progenitors in bone defect repair remain elusive. In this study, we demonstrated that implantation of periosteal-derived mesenchymal progenitor cells (PDMPCs) that overexpressed an N-terminal sonic hedgehog peptide (ShhN) via an adenoviral vector (Ad-ShhN) restored periosteal bone collar formation in a 4-mm segmental bone allograft model in immunodeficient mice. Ad-ShhN enhanced donor cell survival and microvessel formation in collagen scaffold at 2 weeks after surgery and induced donor cell–dependent bone formation at 6 weeks after surgery. Fluorescence-activated cell sorting analysis further showed that Ad-ShhN-PDMPC–seeded scaffold contained a twofold more CD45?Sca-1+CD34+VEGFR2+ endothelial progenitors than Ad-LacZ-PDMPC–seeded scaffold at day 7 after surgery. Ad-ShhN–transduced PDMPCs induced a 1.8-fold more CD31+ microvessel formation than Ad-LacZ–transduced PDMPCs in a coculture of endothelial progenitors and PDMPCs. Taken together, our data show that overexpression of ShhN in mesenchymal progenitors improves bone defect reconstruction by enhancing donor progenitor cell survival, differentiation, and scaffold revascularization at the site of compromised periosteum. Hh agonist–based therapy, therefore, merits further investigation in tissue engineering–based applications aimed at enhancing bone defect repair and reconstruction. PMID:24089140

Huang, Chunlan; Tang, Minghui; Yehling, Eric; Zhang, Xinping

2014-01-01

56

Effect of distraction frequency on bone formation during bone lengthening: a study in chickens.  

PubMed

We compared the effects of two distraction frequencies on bone formation during tibial lengthening by evaluating radiographs, bone mineral density, and histological findings. In 15 mature White Leghorn chickens, both tibiae were distracted at a rate of 0.75 mm/day for 10 days. The distraction frequency was 2 steps (0.375 mm/12 hour) by hand on the right side and 120 steps (0.00625 mm/12 min) by autodistractor on the left. Serial radiographs showed faster bone formation on the 120-step side than on the 2-step side. Bone mineral density on the 120-step side was also higher than that on the 2-step side at all times. On the 2-step side, endochondral ossification was marked in the early stage of distraction; then intramembranous ossification became the main mechanism of bone formation. On the 120-step side, however, intramembranous bone formation predominated throughout the study. Our findings support the contention that, at least in skeletally mature chickens, an increase in the distraction frequency improves osteogenesis during bone lengthening. PMID:14763703

Mizuta, Hiroshi; Nakamura, Eiichi; Mizumoto, Yoshihiko; Kudo, Satoshi; Takagi, Katsumasa

2003-12-01

57

Clay-Enriched Silk Biomaterials for Bone Formation  

PubMed Central

The formation of silk protein/clay composite biomaterials for bone tissue formation is described. Silk fibroin serves as an organic scaffolding material offering mechanical stability suitable for bone specific uses. Clay montmorillonite (Cloisite ® Na+) and sodium silicate are sources of osteoinductive silica-rich inorganic species, analogous to bioactive bioglass-like bone repair biomaterial systems. Different clay particle-silk composite biomaterial films were compared to silk films doped with sodium silicate as controls for support of human bone marrow derived mesenchymal stem cells (hMSCs) in osteogenic culture. The cells adhered and proliferated on the silk/clay composites over two weeks. Quantitative real-time RT-PCR analysis revealed increased transcript levels for alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen type 1 (Col I) osteogenic markers in the cells cultured on the silk/clay films in comparison to the controls. Early evidence for bone formation based on collagen deposition at the cell-biomaterial interface was also found, with more collagen observed for the silk films with higher contents of clay particles. The data suggest that the silk/clay composite systems may be useful for further study toward bone regenerative needs. PMID:21549864

Mieszawska, Aneta J.; Llamas, Jabier Gallego; Vaiana, Christopher A.; Kadakia, Madhavi P.; Naik, Rajesh R.; Kaplan, David L.

2011-01-01

58

The transcriptional cofactor Lbh regulates angiogenesis and endochondral bone formation during fetal bone development.  

PubMed

Lbh is thought to act as a transcriptional cofactor and is highly conserved among species. Here we show that Lbh is expressed in chondrocytes, cells of the perichondrium, and the primary spongiosa in fetal growth plates of mice and chickens. Lbh overexpression in chick wings, using the RCAS-retroviral vector strategy, results in shortened skeletal elements and delayed hypertrophic chondrocyte maturation and bone formation. Additionally, osteoclast and endothelial cell invasion are delayed in the Lbh-overexpressing bones. Finally, we find a dramatic suppression of Runx2 and VEGF mRNAs in chondrocytes and osteoblasts that overexpress Lbh. Strikingly, this abnormal bone development in infected limbs can be rescued by concurrent overexpression of Runx2. These results suggest that during endochondral bone formation, Lbh may negatively regulate vascular invasion and formation of the early ossification center at least in part by interfering with Runx2 and/or VEGF expression. PMID:19607824

Conen, K L; Nishimori, S; Provot, S; Kronenberg, H M

2009-09-15

59

TGF-? and BMP Signaling in Osteoblast Differentiation and Bone Formation  

PubMed Central

Transforming growth factor-beta (TGF-?)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-?/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-?/BMPs is specifically through both canonical Smad-dependent pathways (TGF-?/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-?/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-?/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-?/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-?/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-?/BMP signaling. This review also highlights the different modes of cross-talk between TGF-?/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation. PMID:22298955

Chen, Guiqian; Deng, Chuxia; Li, Yi-Ping

2012-01-01

60

Systemic mesenchymal stem cell administration enhances bone formation in fracture repair but not load-induced bone formation.  

PubMed

Mesenchymal stem cells (MSC) were shown to support bone regeneration, when they were locally transplanted into poorly healing fractures. The benefit of systemic MSC transplantation is currently less evident. There is consensus that systemically applied MSC are recruited to the site of injury, but it is debated whether they actually support bone formation. Furthermore, the question arises as to whether circulating MSC are recruited only in case of injury or whether they also participate in mechanically induced bone formation. To answer these questions we injected green fluorescent protein (GFP)-labelled MSC into C57BL/6J mice, which were subjected either to a femur osteotomy or to non-invasive mechanical ulna loading to induce bone formation. We detected GFP-labelled MSC in the early (day 10) and late fracture callus (day 21) by immunohistochemistry. Stromal cell-derived factor 1 (SDF-1 or CXCL-12), a key chemokine for stem cell attraction, was strongly expressed by virtually all cells near the osteotomy - indicating that SDF-1 may mediate cell migration to the site of injury. We found no differences in SDF-1 expression between the groups. Micro-computed tomography (µCT) revealed significantly more bone in the callus of the MSC treated mice compared to untreated controls. The bending stiffness of callus was not significantly altered after MSC-application. In contrast, we failed to detect GFP-labelled MSC in the ulna after non-invasive mechanical loading. Histomorphometry and µCT revealed a significant load-induced increase in bone formation; however, no further increase was found after MSC administration. Concluding, our results suggest that systemically administered MSC are recruited and support bone formation only in case of injury but not in mechanically induced bone formation. PMID:25552426

Rapp, A E; Bindl, R; Heilmann, A; Erbacher, A; Müller, I; Brenner, R E; Ignatius, A

2015-01-01

61

Bone formation induced by BMP-2 in human osteosarcoma cells  

PubMed Central

Our previous studies demonstrated that BMP-2 inhibits the tumorigenicity of cancer stem cells identified as cells with high aldehyde dehydrogenase activity (ALDH br cells) from the human osteosarcoma cell line OS99-1. We further investigated whether BMP-2 is capable of inducing bone formation in OS99-1 cells. Flow cytometry sorting was used to isolate tumorigenic ALDH br and non-tumorigenic ALDH lo cells. qRT-PCR was used to quantify the gene expression. A xenograft model was used to verify the bone formation in vivo . There was significantly higher mRNA expression of BMPR1B and BMPR2 in ALDH lo cells compared with that in ALDH br cells and the BMPR1B expression in ALDH lo cells was ?8-fold higher compared to that in ALDH br cells. BMP-2 was also found to induce higher transcription of osteogenic markers Runx-2, Osterix (Osx), alkaline phosphatase (ALP) and collagen type I in ALDH lo cells compared to ALDH br cells, which were mediated by the canonical Smad signaling pathway. In vivo , BMP-2 was identified to induce bone formation in both ALDH br and ALDH lo cells. All animals receiving 1×10 4 ALDH lo cells treated with 30 ? g of BMP-2 per animal showed bone formation within 1–2 weeks after injection in mice. Bone formation induced by BMP-2 in ALDH lo cells showed significantly more bone mineral content compared to that in ALDH br cells. BMP-2 induces bone formation in heterogeneous osteosarcoma cells and BMP-2 may have a promising therapeutic role for treating human osteosarcoma by inducing differentiation along an osteogenic pathway. PMID:23900689

WANG, LIN; PARK, PAUL; LA MARCA, FRANK; THAN, KHOI; RAHMAN, SHAYAN; LIN, CHIA-YING

62

Bone formation induced by BMP-2 in human osteosarcoma cells.  

PubMed

Our previous studies demonstrated that BMP-2 inhibits the tumorigenicity of cancer stem cells identified as cells with high aldehyde dehydrogenase activity (ALDH(br) cells) from the human osteosarcoma cell line OS99-1. We further investigated whether BMP-2 is capable of inducing bone formation in OS99-1 cells. Flow cytometry sorting was used to isolate tumorigenic ALDH(br) and non-tumorigenic ALDH(lo) cells. qRT-PCR was used to quantify the gene expression. A xenograft model was used to verify the bone formation in vivo. There was significantly higher mRNA expression of BMPR1B and BMPR2 in ALDH(lo) cells compared with that in ALDH(br) cells and the BMPR1B expression in ALDH(lo) cells was ~8-fold higher compared to that in ALDHbr cells. BMP-2 was also found to induce higher transcription of osteogenic markers Runx-2, Osterix (Osx), alkaline phosphatase (ALP) and collagen type I in ALDH(lo) cells compared to ALDH(br) cells, which were mediated by the canonical Smad signaling pathway. In vivo, BMP-2 was identified to induce bone formation in both ALDH(br) and ALDH(lo) cells. All animals receiving 1 x 10()4 ALDH(lo) cells treated with 30 µg of BMP-2 per animal showed bone formation within 1-2 weeks after injection in mice. Bone formation induced by BMP-2 in ALDH(lo) cells showed significantly more bone mineral content compared to that in ALDH(br) cells. BMP-2 induces bone formation in heterogeneous osteosarcoma cells and BMP-2 may have a promising therapeutic role for treating human osteosarcoma by inducing differentiation along an osteogenic pathway. PMID:23900689

Wang, Lin; Park, Paul; La Marca, Frank; Than, Khoi; Rahman, Shayan; Lin, Chia-Ying

2013-10-01

63

The stimulation of bone formation in vitro by therapeutic ultrasound  

Microsoft Academic Search

A controlled study was performed to evaluate the effects of different ultrasound (US) intensities on 5-day-old mouse calvaria bone in tissue culture. A special technique to apply the US was developed, and the following parameters were measured: collagen and noncollagenous protein (NCP) synthesis (bone formation), and temperature change. It was found that ultrasound at 0.1 W\\/cm 2 (SATA), pulsed 1:4,

Peter Reher; El-Noor I. Elbeshir; Wilson Harvey; Sajeda Meghji; Malcolm Harris

1997-01-01

64

Soluble silica inhibits osteoclast formation and bone resorption in vitro.  

PubMed

Several studies have suggested that silicon (Si) may be essential for the normal development of connective tissue and the skeleton. Positive effects of Si from the diet as well as from Si-containing biomaterials, such as bioactive glass 45S5 (BG), have been demonstrated. Studies have reported that Si stimulates osteoblast proliferation and differentiation. However, the effects of Si on osteoclasts have not been directly addressed. The purpose of the present in vitro study was to clarify if Si has regulatory effects on osteoclast formation and bone resorption. The effects of BG, BG dissolution extracts and Si containing cell culture medium were investigated in a mouse calvarial bone resorption assay and osteoclast formation assays (mouse bone marrow cultures and RAW264.7 cell cultures). We conclude from our results that Si causes significant inhibition of osteoclast phenotypic gene expressions, osteoclast formation and bone resorption in vitro. In conclusion, the present study suggests that Si has a dual nature in bone metabolism with stimulatory effects on osteoblasts and inhibitory effects on osteoclasts. This suggested property of Si might be interesting to further explore in future biomaterials for treatments of bone defects in patients. PMID:24016843

Mladenovi?, Živko; Johansson, Anders; Willman, Britta; Shahabi, Kaveh; Björn, Erik; Ransjö, Maria

2014-01-01

65

Bis(monoacylglycero)phosphate Forms Stable Small Lamellar Vesicle Structures: Insights into Vesicular Body Formation in Endosomes  

PubMed Central

Bis(monoacylglycero)phosphate (BMP) is an unusually shaped lipid found in relatively high percentage in the late endosome. Here, we report the characterization of the morphology and molecular organization of dioleoyl-BMP (DOBMP) with dynamic light scattering, transmission electron microscopy, nuclear magnetic resonance (NMR) spectroscopy, and electron paramagnetic resonance spectroscopy. The morphology of hydrated DOBMP dispersions varies with pH and ionic strength, and DOBMP vesicles are significantly smaller in diameter than phosphatidylcholine dispersions. At neutral pH, DOBMP forms highly structured, clustered dispersions 500 nm in size. On the other hand, at acidic pH, spherically shaped vesicles are formed. NMR and spin-labeled electron paramagnetic resonance demonstrate that DOBMP forms a lamellar mesophase with acyl-chain packing similar to that of other unsaturated phospholipids. 31P NMR reveals an orientation of the phosphate group in DOBMP that differs significantly from that of other phospholipids. These macroscopic and microscopic structural characterizations suggest that the biosynthesis of BMP on the inner luminal membrane of maturing endosomes may possibly produce budded vesicles high in BMP content, which form small vesicular structures stabilized by the physical properties of the BMP lipid. PMID:19254543

Frederick, Thomas E.; Chebukati, Janetricks N.; Mair, Chad E.; Goff, Philip C.; Fanucci, Gail E.

2009-01-01

66

Porphyromonas gingivalis infection increases osteoclastic bone resorption and osteoblastic bone formation in a periodontitis mouse model  

PubMed Central

Background Porphyromonas gingivalis has been shown to invade osteoblasts and inhibit their differentiation and mineralization in vitro. However, it is unclear if P. gingivalis can invade osteoblasts in vivo and how this would affect alveolar osteoblast/osteoclast dynamics. This study aims to answer these questions using a periodontitis mouse model under repetitive P. gingivalis inoculations. Methods For 3-month-old BALB/cByJ female mice, 109 CFU of P. gingivalis were inoculated onto the gingival margin of maxillary molars 4 times at 2-day intervals. After 2 weeks, another 4 inoculations at 2-day intervals were applied. Calcein was injected 7 and 2 days before sacrificing animals to label the newly formed bone. Four weeks after final inoculation, mice were sacrificed and maxilla collected. Immunohistochemistry, micro-CT, and bone histomorphometry were performed on the specimens. Sham infection with only vehicle was the control. Results P. gingivalis was found to invade gingival epithelia, periodontal ligament fibroblasts, and alveolar osteoblasts. Micro-CT showed alveolar bone resorption and significant reduction of bone mineral density and content in the infected mice compared to the controls. Bone histomorphometry showed a decrease in osteoblasts, an increase in osteoclasts and bone resorption, and a surprisingly increased osteoblastic bone formation in the infected mice compared to the controls. Conclusions P. gingivalis invades alveolar osteoblasts in the periodontitis mouse model and cause alveolar bone loss. Although P. gingivalis appears to suppress osteoblast pool and enhance osteoclastic bone resorption, the bone formation capacity is temporarily elevated in the infected mice, possibly via some anti-microbial compensational mechanisms. PMID:25027664

2014-01-01

67

Re-evaluating the induction of bone formation in primates.  

PubMed

The molecular cloning of the osteogenic proteins of the transforming growth factor-? (TGF-?) supergene family and the results of numerous pre-clinical studies in several mammalian species including non-human primates, have prematurely convinced molecular biologists, tissue engineers and skeletal reconstructionists alike to believe that single recombinant human bone morphogenetic/osteogenic proteins (hBMPs/OPs) would result in tissue induction when translated in clinical contexts. This theoretical potential has not been translated to acceptable clinical results. Clinical trials in craniofacial and orthopedic applications such as mandibular reconstruction and sinus-lift operations have indicated that supra physiological doses of a single recombinant human protein are needed to induce unacceptable tissue regeneration whilst incurring significant costs without achieving equivalence to autogenous bone grafts. The acid test for clinically relevant bone tissue engineering should now become the concept of clinically significant osteoinduction, whereby the regenerated bone is readily identifiable on radiographic examination by virtue of its opacity and trabecular architecture. The need for alternatives to the hBMPs/OPs is now felt more acutely following reported complications and performance failure associated with the clinical use of hBMP-2 and hOP-1 (BMP-7). Because of the often substandard regeneration of clinical defects implanted with hBMPs/OPs, we now need to finally deal with the provocative question: are the hBMPs/OPs the only initiators of the induction of bone formation in pre-clinical and clinical contexts? The rapid induction of bone formation by the hTGF-?? isoform in heteropic intramuscular sites of the Chacma baboon Papio ursinus together with TGF-??, TGF-??, BMP-2, BMP-3, OP-1, RUNX-2 and Osteocalcin up-regulation and expression, hyper cellular osteoblastic activity, osteoid synthesis, angiogenesis and capillary sprouting are the molecular and morphological foundation for the induction of bone formation in clinical contexts. The induction of bone as initiated by hTGF-?3 when implanted in the rectus abdominis muscle of P. ursinus is via the BMPs/OPs pathway with hTGF-?? controlling the induction of bone formation by regulating the expression of BMPs/OPs via Noggin expression, eliciting the induction of bone formation by up-regulating endogenous BMPs/OPs and it is blocked by hNoggin, providing insights into performance failure of hBMPs/OPs in clinical contexts. Physiological expression of BMPs/OPs genes upon implantation of hTGF-?? may escape the antagonist expression of Noggin and other inhibitors, whereas direct application of hBMPs/OPs, representing a later by-product step of the bone induction cascade as set by the TGF-?? master gene in primates, sets into motion Noggin' antagonist action, as shown by the limited effectiveness of hBMPs/OPs in clinical contexts. The unprecedented induction of bone formation by 250 ?g hTGF-?? when combined with coral-derived macroporous constructs is the novel molecular and morphological frontier for the induction of bone formation in man. The induction of bone by hTGF-?? has been thus translated in clinical contexts to treat a large mandibular defect in a pediatric patient; 30 months after implantation of 250 ?g hTGF-?? per gram of human demineralized bone matrix, radiographic analyses show the reconstruction of the avulsed large mandibular segment including the induction of the avulsed coronoid process. PMID:25155544

Ripamonti, Ugo; Duarte, Raquel; Ferretti, Carlo

2014-11-01

68

Human Placenta-Derived Adherent Cells Prevent Bone loss, Stimulate Bone formation, and Suppress Growth of Multiple Myeloma in Bone  

PubMed Central

Human placenta has emerged as a valuable source of transplantable cells of mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes, including enhanced engraftment of hematopoietic stem cells, modulation of inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs) are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple myeloma is closely associated with induction of bone disease and large lytic lesions, which are often not repaired and are usually the sites of relapses. We evaluated the antimyeloma therapeutic potential, in vivo survival, and trafficking of PDACs in the severe combined immunodeficiency (SCID)–rab model of medullary myeloma-associated bone loss. Intrabone injection of PDACs into non-myelomatous and myelomatous implanted bone in SCID-rab mice promoted bone formation by stimulating endogenous osteoblastogenesis, and most PDACs disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone disease and tumor growth were dose-dependent and comparable with those of fetal human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma cell growth rate in vitro was lower in coculture with PDACs than with MSCs from human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast precursors and inhibited their differentiation. This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis. PMID:21732484

Li, Xin; Ling, Wen; Pennisi, Angela; Wang, Yuping; Khan, Sharmin; Heidaran, Mohammad; Pal, Ajai; Zhang, Xiaokui; He, Shuyang; Zeitlin, Andy; Abbot, Stewart; Faleck, Herbert; Hariri, Robert; Shaughnessy, John D.; van Rhee, Frits; Nair, Bijay; Barlogie, Bart; Epstein, Joshua; Yaccoby, Shmuel

2011-01-01

69

The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro  

Microsoft Academic Search

In this study, we have determined the effect of the divalent strontium salt S12911 on bone cell replication and bone formation in two culture systems. In the first series of experiments, half-calvariae of newborn rats were cultured with S12911 from 24 to 96 h and labeled with 3H-thymidine for the last 6 h of culture or treated with S12911 for

E. Canalis; M. Hott; P. Deloffre; Y. Tsouderos; P. J. Marie

1996-01-01

70

Non-Linear Pattern Formation in Bone Growth and Architecture  

PubMed Central

The three-dimensional morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatiotemporal trajectory to acquire optimal architecture. On a cellular, micro-anatomical scale, what mechanisms coordinate the activity of osteoblasts and osteoclasts to produce complex and efficient bone architectures? One mechanism is examined here – chaotic non-linear pattern formation (NPF) – which underlies in a unifying way natural structures as disparate as trabecular bone, swarms of birds flying, island formation, fluid turbulence, and others. At the heart of NPF is the fact that simple rules operating between interacting elements, and Turing-like interaction between global and local signals, lead to complex and structured patterns. The study of “group intelligence” exhibited by swarming birds or shoaling fish has led to an embodiment of NPF called “particle swarm optimization” (PSO). This theoretical model could be applicable to the behavior of osteoblasts, osteoclasts, and osteocytes, seeing them operating “socially” in response simultaneously to both global and local signals (endocrine, cytokine, mechanical), resulting in their clustered activity at formation and resorption sites. This represents problem-solving by social intelligence, and could potentially add further realism to in silico computer simulation of bone modeling. What insights has NPF provided to bone biology? One example concerns the genetic disorder juvenile Pagets disease or idiopathic hyperphosphatasia, where the anomalous parallel trabecular architecture characteristic of this pathology is consistent with an NPF paradigm by analogy with known experimental NPF systems. Here, coupling or “feedback” between osteoblasts and osteoclasts is the critical element. This NPF paradigm implies a profound link between bone regulation and its architecture: in bone the architecture is the regulation. The former is the emergent consequence of the latter. PMID:25653638

Salmon, Phil

2014-01-01

71

Transgenic overexpression of bone morphogenetic protein 11 propeptide in skeleton enhances bone formation.  

PubMed

Bone morphogenetic protein 11 (BMP11) is a key regulatory protein in skeletal development. BMP11 propeptide has been shown to antagonize GDF11 activity in vitro. To explore the role of BMP11 propeptide in skeletal formation in vivo, we generated transgenic mice with skeleton-specific overexpression of BMP11 propeptide cDNA. The mice showed a transformation of the seventh cervical vertebra into a thoracic vertebra in our previous report. Presently, further characterizations of the transgenic mice indicated that ossification in calvatia was dramatically enhanced in transgenic fetuses at 16.5 dpc in comparison with their wild-type littermates. At 10 weeks of age, bone mineral content and bone mineral density were significantly (P<0.05) higher in transgenic mice than that in their wild-type littermates based on dual energy X-ray absorptiometry analysis. The relative trabecular bone volume measured by histological analysis was dramatically increased in transgenic mice compared with their wild-type littermates. The enhanced bone formations in the transgenic mice appear to result from increase osteoblast activities as the expressions of four osteoblast markers - ?1 type 1 collagen, osteocalcin, alkaline phosphatase and phex were significantly higher in transgenic fetuses than that in their wild-type littermates. These results suggest that over-expression of BMP11 propeptide stimulates bone formation by increasing osteoblast cell functions. PMID:22093826

Li, Zicong; Zeng, Fang; Mitchell, Alva D; Kim, Yong Soo; Wu, Zhenfang; Yang, Jinzeng

2011-12-16

72

DYSAPOPTOSIS OF OSTEOBLASTS AND OSTEOCYTES INCREASES CANCELLOUS BONE FORMATION BUT EXAGGERATES BONE POROSITY WITH AGE  

PubMed Central

Skeletal aging is accompanied by decreased cancellous bone mass and increased formation of pores within cortical bone. The latter accounts for a large portion of the increase in non-vertebral fractures after age 65 in humans. We selectively deleted Bak and Bax, two genes essential for apoptosis, in two types of terminally differentiated bone cells: the short-lived osteoblasts that elaborate the bone matrix, and the long-lived osteocytes that are immured within the mineralized matrix and choreograph the regeneration of bone. Attenuation of apoptosis in osteoblasts increased their working lifespan and thereby cancellous bone mass in the femur. In long-lived osteocytes, however, it caused dysfunction with advancing age and greatly magnified intracortical femoral porosity associated with increased production of receptor activator of nuclear factor-?B ligand and vascular endothelial growth factor. Increasing bone mass by artificial prolongation of the inherent lifespan of short-lived osteoblasts, while exaggerating the adverse effects of aging on long-lived osteocytes, highlights the seminal role of cell age in bone homeostasis. In addition, our findings suggest that distress signals produced by old and/or dysfunctional osteocytes are the culprits of the increased intracortical porosity in old age. PMID:23761243

Jilka, Robert L.; O’Brien, Charles A.; Roberson, Paula K.; Bonewald, Lynda F.; Weinstein, Robert S.; Manolagas, Stavros C.

2013-01-01

73

Active multilayered capsules for in vivo bone formation  

PubMed Central

Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled. PMID:20160118

Facca, S.; Cortez, C.; Mendoza-Palomares, C.; Messadeq, N.; Dierich, A.; Johnston, A. P. R.; Mainard, D.; Voegel, J.-C.; Caruso, F.; Benkirane-Jessel, N.

2010-01-01

74

MicroRNA control of bone formation and homeostasis  

PubMed Central

MicroRNAs (miRNAs) repress cellular protein levels to provide a sophisticated parameter of gene regulation that coordinates a broad spectrum of biological processes. Bone organogenesis is a complex process involving the differentiation and crosstalk of multiple cell types for formation and remodeling of the skeleton. Inhibition of mRNA translation by miRNAs has emerged as an important regulator of developmental osteogenic signaling pathways, osteoblast growth and differentiation, osteoclast-mediated bone resorption activity and bone homeostasis in the adult skeleton. miRNAs control multiple layers of gene regulation for bone development and postnatal functions, from the initial response of stem/progenitor cells to the structural and metabolic activity of the mature tissue. This Review brings into focus an emerging concept of bone-regulating miRNAs, the evidence for which has been gathered largely from in vivo mouse models and in vitro studies in human and mouse skeletal cell populations. Characterization of miRNAs that operate through tissue-specific transcription factors in osteoblast and osteoclast lineage cells, as well as intricate feedforward and reverse loops, has provided novel insights into the supervision of signaling pathways and regulatory networks controlling normal bone formation and turnover. The current knowledge of miRNAs characteristic of human pathologic disorders of the skeleton is presented with a future goal towards translational studies. PMID:22290358

Lian, Jane B.; Stein, Gary S.; van Wijnen, Andre J.; Stein, Janet L.; Hassan, Mohammad Q.; Gaur, Tripti; Zhang, Ying

2013-01-01

75

Effect of zinc supplementation on bone formation in hemodialysis patients with normal or low turnover bone.  

PubMed

Abstract Zinc (Zn) is an essential trace element, which has been shown to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption in vitro. In thalassemia, major patients Zn supplementation was reported to increase whole-body bone mineral content and areal bone mineral density. Therefore, we investigated the effect of Zn supplementation on bone formation in hemodialysis (HD) patients. Nine male patients with age of 66 (35-78) years indicated by median (range), HD vintage of 57 (4-97) months and serum intact parathyroid hormone (PTH) of 113 (6-310) pg/mL were supplemented with polaprezinc containing 34?mg Zn/day for 18 months. Doses of vitamin D were not changed during supplementation. Blood was collected at baseline, 3, 6, 12 and 18 months. Serum Zn increased significantly from 58 (52-65)??g/dL to 71 (57-93) ?g/dL at three months and remained unchanged until 18 months. No changes were observed in serum intact PTH during supplementation. Although we found no changes in serum bone alkaline phosphatase (BAP) during Zn supplementation analyzed by Friedman test and Scheffe post hoc test, a significant trend of increase in serum BAP was verified by Jonckheere-Terpstra test (p?=?0.0409). On the contrary, there was no trend in serum TRACP5b by Jonckheere-Terpstra test. Therefore, we suggested the effect of Zn supplementation on promoting bone formation, not affected by the status of PTH and vitamin D, in HD patients with normal or low turnover bone. PMID:25207792

Shiota, Jun; Tagawa, Hitoshi; Izumi, Naoki; Higashikawa, Shingo; Kasahara, Hitoshi

2015-02-01

76

Bone formation in rabbit cancellous bone explant culture model is enhanced by mechanical load  

PubMed Central

Background When studying and designing an artificial bone in vitro with similar features and functionality of natural bone by tissue engineering technology, the culturing environment, especially the mechanical environment is supposed to be an important factor, because a suitable mechanical environment in vitro may improve the adaptability of the planted-in tissue engineering bone in the body. Unfortunately, up to now, the relationship between mechanical stimuli and natural bone growth has not yet been precisely determined, and it is so imperative for a prior study on effect of mechanical loading on growth of the natural bone cultured in vitro. Methods Under sterile conditions, explant models of rabbit cancellous bone with 3?mm in thickness and 8?mm in diameter were prepared and cultured in a dynamic loading and circulating perfusion bioreactor system. By Micro-CT scanning, a 3D model for finite element (FEM) analysis was achieved. According to the results of FEM analysis and physiological load bearing capacity of the natural bone, these models were firstly subjected to mechanical load with 1Hz frequency causing average apparent strain of 1000 ??, 2000 ??, 3000 ?? and 4000 ?? respectively for 30?min every day, activities of alkaline phosphatase (AKP) were detected on the 5th and the 14th loading day and on the 14th and the 21st day, mechanical properties, tissue mineral density (TMD) of the bone explant models were investigated and Von-kossa staining and fluorescence double labeling assays were conducted to evaluate whether there were fresh osteoid in the bone explant models. In addition, Western blot, Elisa and Real-time PCR were employed to analyze expression of Collagen-I (COL-1), bone morphogenetic protein-2 (BMP-2) and osteoprotegerin (OPG) protein and RNA. Results The explant models of rabbit cancellous bone prepared under sterile conditions grew well in the bioreactor system. With the increasing culturing time and load levels, bone explant models in groups with 1000 ?? and 2000 ?? average apparent strain experienced improving mechanical properties and TMD (P<0.05), and results of Von-kossa staining and fluorescence double labeling also showed apparent fresh osteoid formation. Under the same loading conditions, a up-regulations in protein and RNA of COL-1, BMP-2 and OPG were detected, especially, relative genes notably expressed after 21?days. Conclusion Our study demonstrated that mechanical load could improve function and activity of osteoblasts in explant models of cancellous bone. Through regulations of COL-1, OPG and BMP-2 secreted by osteoblasts, the mechanical load could improve the tissue structural density and stiffness due to formation of fresh osteoid. PMID:23597232

2013-01-01

77

Immunolocalization of markers for bone formation during guided bone regeneration in osteopenic rats.  

PubMed

Objective The aim of this paper was to evaluate the repair of onlay autogenous bone grafts covered or not covered by an expanded polytetrafluoroethylene (e-PTFE) membrane using immunohistochemistry in rats with induced estrogen deficiency. Material and Methods Eighty female rats were randomly divided into two groups: ovariectomized (OVX) and with a simulation of the surgical procedure (SHAM). Each of these groups was again divided into groups with either placement of an autogenous bone graft alone (BG) or an autogenous bone graft associated with an e-PTFE membrane (BGM). Animals were euthanized on days 0, 7, 21, 45, and 60. The specimens were subjected to immunohistochemistry for bone sialoprotein (BSP), osteonectin (ONC), and osteocalcin (OCC). Results All groups (OVX+BG, OVX+BMG, SHAM+BG, and SHAM+BMG) showed greater bone formation, observed between 7 and 21 days, when BSP and ONC staining were more intense. At the 45-day, the bone graft showed direct bonding to the recipient bed in all specimens. The ONC and OCC showed more expressed in granulation tissue, in the membrane groups, independently of estrogen deficiency. Conclusions The expression of bone forming markers was not negatively influenced by estrogen deficiency. However, the markers could be influenced by the presence of the e-PTFE membrane. PMID:25591022

Tera, Tábata de Mello; Nascimento, Rodrigo Dias; Prado, Renata Falchete do; Santamaria, Mauro Pedrine; Jardini, Maria Aparecida Neves

2014-12-01

78

Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation  

Microsoft Academic Search

Osteocytes are the most abundant cells in bone and are ideally located to influence bone turnover through their syncytial relationship with surface bone cells. Osteocyte-derived signals have remained largely enigmatic, but it was recently reported that human osteocytes secrete sclerostin, an inhibitor of bone formation. Absent sclerostin protein results in the high bone mass clinical disorder sclerosteosis. Here we report

Kenneth E. S. Poole; Rutger L. van Bezooijen; Nigel Loveridge; Herman Hamersma; Socrates E. Papapoulos; Clemens W. Löwik; Jonathan Reeve

2005-01-01

79

Interference with the Microenvironment Support Impairs the De Novo Formation of Bone Metastasis In Vivo  

Microsoft Academic Search

Interference with the microenvironmental growth support is an attractive therapeutic strategy for repressing metastatic tumor growth. Bone is a highly dynamic tissue that is continuously remodeled by bone resorption and subsequent bone formation. Growth factors supporting bone metastatic growth are released especially during bone resorption. Differently from most other tissues, drugs that can limit local turnover, such as bisphosphonates, are

Gabri van der Pluijm; Ivo Que; Bianca Sijmons; Jeroen T Buijs; Antoinette Wetterwald; George N Thalmann; Socrates E Papapoulos; Marco G Cecchini

80

Surface microcracks signal osteoblasts to regulate alignment and bone formation.  

PubMed

Microcracks are present in bone and can result from fatigue damage due to repeated, cyclically applied stresses. From a mechanical point, microcracks can dissipate strain energy at the advancing tip of a crack to improve overall bone toughness. Physiologically, microcracks are thought to trigger bone remodeling. Here, we examine the effect of microcracks specifically on osteoblasts, which are bone-forming cells, by comparing cell responses on microcracked versus non-microcracked hydroxyapatite (HA) specimens. Osteoblast attachment was found to be greater on microcracked HA specimens (p<0.05). More importantly, we identified the preferential alignment of osteoblasts in the direction of the microcracks on HA. Cells also displayed a preferential attachment that was 75 to 90 ?m away from the microcrack indent. After 21 days of culture, osteoblast maturation was notably enhanced on the HA with microcracks, as indicated by increased alkaline phosphatase activity and gene expression. Furthermore, examination of bone deposition by confocal laser scanning microscopy indicated preferential mineralization at microcrack indentation sites. Dissolution studies indicate that the microcracks increase calcium release, which could contribute to osteoblast responses. Our findings suggest that microcracks signal osteoblast attachment and bone formation/healing. PMID:25280696

Shu, Yutian; Baumann, Melissa J; Case, Eldon D; Irwin, Regina K; Meyer, Sarah E; Pearson, Craig S; McCabe, Laura R

2014-11-01

81

Fresh-frozen allografts combined with bovine bone mineral enhance bone formation in sinus augmentation.  

PubMed

We evaluated histologically, histomorphometrically, and tomographically the effects of the association of fresh-frozen bone allograft (FFB) with bovine bone mineral (BBM) in maxillary sinus floor augmentation. In total, 34 maxillary sinuses from 29 patients, with a mean age of 51.32 (±6.44) years, underwent sinus augmentation. Patients were divided into control and test groups (17 sinuses each). The controls were grafted with allograft bone, and the test group received a combination of FFB and BBM at a 2:1 ratio. After 6 months, bone samples were collected for histological and histomorphometric examinations. The implant survival rates were 93.02% (control group) and 100% (test group) at 6 months after functional loading. Median volumetric reductions of 28.32% (17.05-44.05) and 12.62% (5.65-16.87) were observed for the control and test groups, respectively. Statistically significant histomorphometric differences were found between the control and test groups regarding newly formed bone 12.54% (10.50-13.33) vs. 24.42% (17.62-35.92), p?bone 48.34% (39.03-54.42) vs. 61.32% (50.61-64.96), p?=?0.007, and connective tissue 51.66% (45.57-60.97) vs. 39.30% (35.03-49.37), p?=?0.007. The addition of BBM to allograft bone in maxillary sinus augmentation resulted in higher percentages of new bone formation and total bone, and permitted implant placement with a low rate of osseointegration failure at the 6-month follow-up. PMID:25245781

Sehn, Felipe Perraro; Dias, Rafael Rodrigues; de Santana Santos, Thiago; Silva, Erick Ricardo; Salata, Luiz Antonio; Chaushu, Gavriel; Xavier, Samuel Porfírio

2015-02-01

82

Transgenic overexpression of bone morphogenetic protein 11 propeptide in skeleton enhances bone formation  

Technology Transfer Automated Retrieval System (TEKTRAN)

Bone morphogenetic protein 11 (BMP11) is a key regulatory protein in skeletal development. BMP11 propeptide has been shown to antagonize GDF11 activity in vitro. To explore the role of BMP11 propeptide in skeletal formation in vivo, we generated transgenic mice with skeleton-specific overexpression...

83

Static and dynamic osteogenesis: two different types of bone formation.  

PubMed

The onset and development of intramembranous ossification centers in the cranial vault and around the shaft of long bones in five newborn rabbits and six chick embryos were studied by light (LM) and transmission electron microscopy (TEM). Two subsequent different types of bone formation were observed. We respectively named them static and dynamic osteogenesis, because the former is characterized by pluristratified cords of unexpectedly stationary osteoblasts, which differentiate at a fairly constant distance (28+/-0.4 microm) from the blood capillaries, and the latter by the well-known typical monostratified laminae of movable osteoblasts. No significant structural and ultrastructural differences were found between stationary and movable osteoblasts, all being polarized secretory cells joined by gap junctions. However, unlike in typical movable osteoblastic laminae, stationary osteoblasts inside the cords are irregularly arranged, variously polarized and transform into osteocytes, clustered within confluent lacunae, in the same place where they differentiate. Static osteogenesis is devoted to the building of the first trabecular bony framework having, with respect to the subsequent bone apposition by typical movable osteoblasts, the same supporting function as calcified trabeculae in endochondral ossification. In conclusion, it appears that while static osteogenesis increases the bone external size, dynamic osteogenesis is mainly involved in bone compaction, i.e., in filling primary haversian spaces with primary osteons. PMID:12478364

Ferretti, Marzia; Palumbo, Carla; Contri, Miranda; Marotti, Gastone

2002-12-01

84

Multi-protein delivery by nanodiamonds promotes bone formation.  

PubMed

Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE(®) for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation. PMID:24045646

Moore, L; Gatica, M; Kim, H; Osawa, E; Ho, D

2013-11-01

85

Multi-protein Delivery by Nanodiamonds Promotes Bone Formation  

PubMed Central

Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE® for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation. PMID:24045646

Moore, L.; Gatica, M.; Kim, H.; Osawa, E.; Ho, D.

2013-01-01

86

BMP-13 Emerges as a Potential Inhibitor of Bone Formation  

PubMed Central

Bone morphogenetic protein-13 (BMP-13) plays an important role in skeletal development. In the light of a recent report that mutations in the BMP-13 gene are associated with spine vertebral fusion in Klippel-Feil syndrome, we hypothesized that BMP-13 signaling is crucial for regulating embryonic endochondral ossification. In this study, we found that BMP-13 inhibited the osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells (BM MSCs) in vitro. The endogenous BMP-13 gene expression in MSCs was examined under expansion conditions. The MSCs were then induced to differentiate into osteoblasts in osteo-inductive medium containing exogenous BMP-13. Gene expression was analysed by real-time PCR. Alkaline phosphatase (ALP) expression and activity, proteoglycan (PG) synthesis and matrix mineralization were assessed by cytological staining or ALP assay. Results showed that endogenous BMP-13 mRNA expression was higher than BMP-2 or -7 during MSC growth. BMP-13 supplementation strongly inhibited matrix mineralization and ALP activity of osteogenic differentiated MSCs, yet increased PG synthesis under the same conditions. In conclusion, BMP-13 inhibited osteogenic differentiation of MSCs, implying that functional mutations or deficiency of BMP-13 may allow excess bone formation. Our finding provides an insight into the molecular mechanisms and the therapeutic potential of BMP-13 in restricting pathological bone formation. PMID:19240811

Shen, Bojiang; Bhargav, Divya; Wei, Aiqun; Williams, Lisa A; Tao, Helen; Ma, David D F; Diwan, Ashish D

2009-01-01

87

Biologic properties of nano-hydroxyapatite: An in vivo study of calvarial defects, ectopic bone formation and bone implantation.  

PubMed

This study investigated the biologic properties of nano-hydroxyapatite (nHAp) using the rat calvarial defect, ectopic bone formation, and rabbit tibia implant installation models. Animals were divided into two groups: those implanted with nHAp, and negative controls (Collagen). Eight weeks after creating an 8 mm calvarial defect, bone regeneration was evaluated radiographically and histologically. To investigate ectopic bone formation, materials were injected into the right thigh muscle and were evaluated after 8 weeks. nHAp coated implant and conventional titanium implant were placed bilaterally in rabbit tibias. After 4 weeks, bone-implant contact (BIC), new bone area inside the thread, and removal torque were measured. In the calvarial defect model, radiographic and histologic analysis showed more bone formation in the nHAp Group; particularly, histologically assessed bone area (p=0.034) and microcomputed tomography assessed bone mineral density (p=0.034). In the ectopic bone formation model, calcification and expression of osteogenic biomarkers were seen in the nHAp-injected samples but in none of the controls. nHAp coated implant resulted in increased BIC, new bone area, and increased removal torque, with statistical significance for BIC (p=0.034). This study suggests that nHAp has potential as a coating material for dental implant surfaces and as a bone graft material. PMID:25585978

Pang, Kang-Mi; Lee, Jeong-Keun; Seo, Young-Kwon; Kim, Soung-Min; Kim, Myung-Jin; Lee, Jong-Ho

2015-01-01

88

Targeted deletion of Sost distal enhancer increases bone formation and bone mass  

PubMed Central

The Wnt antagonist Sost has emerged as a key regulator of bone homeostasis through the modulation of Lrp4/5/6 Wnt coreceptors. In humans, lack of Sclerostin causes sclerosteosis and van Buchem (VB) disease, two generalized skeletal hyperostosis disorders that result from hyperactive Wnt signaling. Unlike sclerosteosis, VB patients lack SOST coding mutations but carry a homozygous 52 kb noncoding deletion that is essential for the transcriptional activation of SOST in bone. We recently identified a putative bone enhancer, ECR5, in the VB deletion region, and showed that the transcriptional activity of ECR5 is controlled by Mef2C transcription factor in vitro. Here we report that mice lacking ECR5 or Mef2C through Col1-Cre osteoblast/osteocyte-specific ablation result in high bone mass (HBM) due to elevated bone formation rates. We conclude that the absence of the Sost-specific long-range regulatory element ECR5 causes VB disease in rodents, and that Mef2C is the main transcription factor responsible for ECR5-dependent Sost transcriptional activation in the adult skeleton. PMID:22886088

Collette, Nicole M.; Genetos, Damian C.; Economides, Aris N.; Xie, LiQin; Shahnazari, Mohammad; Yao, Wei; Lane, Nancy E.; Harland, Richard M.; Loots, Gabriela G.

2012-01-01

89

Ectopic bone formation induced by biodegradable hydrogels incorporating bone morphogenetic protein.  

PubMed

Biodegradable hydrogels were prepared from gelatin by glutaraldehyde cross-linking for release matrix of recombinant human bone morphogenetic protein-2 (BMP-2). BMP-2 solution was impregnated into the dried hydrogels to prepare BMP-2-incorporating gelatin hydrogels. In the in vitro study, enhanced retention of BMP-2 was observed from the BMP-2-incorporating gelatin hydrogels after an initial burst of BMP-2 incorporated initially in the hydrogel. Following subcutaneous implantation of (125)I-labeled BMP-2-incorporating gelatin hydrogels in the back of mice, the radioactivity remaining in the hydrogels was measured to estimate the in vivo release profile of BMP-2. It was found that BMP-2 was retained in the hydrogels for longer than 30 days, whereas 99% of BMP-2 injected in the solution form was cleared from the injected site within one day, completely disappearing within 3 days. Ectopic bone formation studies demonstrated that BMP-2-incorporating gelatin hydrogels exhibited a more potent ability for bone induction than solution injection of BMP-2. This finding indicates that enhanced retention of BMP-2 is promotes its ability to induce ectopic bone formation. PMID:9648026

Yamamoto, M; Tabata, Y; Ikada, Y

1998-01-01

90

Pharmacological inhibition of Dock5 prevents osteolysis by affecting osteoclast podosome organization while preserving bone formation.  

PubMed

Osteoporosis is caused by excessive activity of bone-degrading osteoclasts over bone-forming osteoblast. Standard antiosteolytic treatments inhibit bone resorption by inducing osteoclast loss, with the adverse effect of hindering also bone formation. Formation of the osteoclast sealing zone requires Dock5, a guanine nucleotide exchange factor for the small GTPase Rac, and C21, a chemical inhibitor of Dock5, decreases bone resorption by cultured osteoclasts. Here we show that C21 directly inhibits the exchange activity of Dock5 and disrupts osteoclast podosome organization. Remarkably, C21 administration protects mice against bone degradation in models recapitulating major osteolytic diseases: menopause, rheumatoid arthritis and bone metastasis. Furthermore, C21 administration does not affect bone formation and is not toxic. Our results validate the pharmacological inhibition of Dock5 as a novel therapeutic route for fighting osteolytic diseases while preserving bone formation. PMID:25645278

Vives, Virginie; Cres, Gaëlle; Richard, Christian; Busson, Muriel; Ferrandez, Yann; Planson, Anne-Gaelle; Zeghouf, Mahel; Cherfils, Jacqueline; Malaval, Luc; Blangy, Anne

2015-01-01

91

Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis  

Microsoft Academic Search

Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears (Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured

Seth W. Donahue; Sarah A. Galley; Michael R. Vaughan; Patricia Patterson-Buckendahl; Laurence M. Demers; Josef L. Vance; Meghan E. McGee

2006-01-01

92

Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats  

PubMed Central

Background Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment. Methods Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into five groups. The first group served as negative control and the grafts were rinsed in saline before implantation. In the second and third groups, the grafts were soaked in a zoledronic acid solution (0.5 mg/ml) for 5 seconds and 10 minutes respectively before being rinsed in saline. In the fourth group, 8 ?L of zoledronic acid solution (0.5 mg/ml) was pipetted onto the freeze-dried grafts without rinsing. The fifth group served as positive control and the rats were given zoledronic acid (0.1 mg/kg) systemically as a single injection two weeks after surgery. The grafts were harvested at 6 weeks and analysed with histomorphometry, evaluating the ingrowth distance of new bone into the graft as an equivalent to the anabolic osteoblast effect and the amount (bone volume/total volume; BV/TV) of remaining bone in the remodelled graft as equivalent to the catabolic osteoclast effect. Results In all chambers, almost the entire graft had been revascularized but only partly remodelled at harvest. The ingrowth distance of new bone into the graft was lower in grafts soaked in zoledronic acid for 10 minutes compared to control (p = 0.007). In all groups receiving zoledronic acid, the BV/TV was higher compared to control. Conclusions This study found a strong inhibitory effect on bone resorption by bisphosphonates but also a limited inhibition of the ingrowth of new bone. Local treatment at surgery resulted in stronger inhibition of both resorption and bone formation compared to systemic treatment. PMID:23217097

2012-01-01

93

Does locally delivered Zoledronate influence peri-implant bone formation? - Spatio-temporal monitoring of bone remodeling in vivo.  

PubMed

Bisphosphonates are known for their strong inhibitory effect on bone resorption. Their influence on bone formation however is less clear. In this study we investigated the spatio-temporal effect of locally delivered Zoledronate on peri-implant bone formation and resorption in an ovariectomized rat femoral model. A cross-linked hyaluronic acid hydrogel was loaded with the drug and applied bilaterally in predrilled holes before inserting polymer screws. Static and dynamic bone parameters were analyzed based on in vivo microCT scans performed first weekly and then biweekly. The results showed that the locally released Zoledronate boosted bone formation rate up to 100% during the first 17 days after implantation and reduced the bone resorption rate up to 1000% later on. This shift in bone remodeling resulted in an increase in bone volume fraction (BV/TV) by 300% close to the screw and 100% further away. The double effect on bone formation and resorption indicates a great potential of Zoledronate-loaded hydrogel for enhancement of peri-implant bone volume which is directly linked to improved implant fixation. PMID:25241159

Kettenberger, Ulrike; Ston, Julien; Thein, Eric; Procter, Philip; Pioletti, Dominique P

2014-12-01

94

Inkjet-Based Biopatterning of Bone Morphogenetic Protein-2 to Spatially Control Calvarial Bone Formation  

PubMed Central

The purpose of this study was to demonstrate spatial control of osteoblast differentiation in vitro and bone formation in vivo using inkjet bioprinting technology and to create three-dimensional persistent bio-ink patterns of bone morphogenetic protein-2 (BMP-2) and its modifiers immobilized within microporous scaffolds. Semicircular patterns of BMP-2 were printed within circular DermaMatrix™ human allograft scaffold constructs. The contralateral halves of the constructs were unprinted or printed with BMP-2 modifiers, including the BMP-2 inhibitor, noggin. Printed bio-ink pattern retention was validated using fluorescent or 125I-labeled bio-inks. Mouse C2C12 progenitor cells cultured on patterned constructs differentiated in a dose-dependent fashion toward an osteoblastic fate in register to BMP-2 patterns. The fidelity of spatial restriction of osteoblastic differentiation at the boundary between neighboring BMP-2 and noggin patterns improved in comparison with patterns without noggin. Acellular DermaMatrix constructs similarly patterned with BMP-2 and noggin were then implanted into a mouse calvarial defect model. Patterns of bone formation in vivo were comparable with patterned responses of osteoblastic differentiation in vitro. These results demonstrate that three-dimensional biopatterning of a growth factor and growth factor modifier within a construct can direct cell differentiation in vitro and tissue formation in vivo in register to printed patterns. PMID:20028232

Miller, Eric D.; DeCesare, Gary E.; Usas, Arvydas; Lensie, Emily L.; Bykowski, Michael R.; Huard, Johnny; Weiss, Lee E.; Losee, Joseph E.; Campbell, Phil G.

2010-01-01

95

Biglycan modulates angiogenesis and bone formation during fracture healing.  

PubMed

Matrix proteoglycans such as biglycan (Bgn) dominate skeletal tissue and yet its exact role in regulating bone function is still unclear. In this paper we describe the potential role of (Bgn) in the fracture healing process. We hypothesized that Bgn could regulate fracture healing because of previous work showing that it can affect normal bone formation. To test this hypothesis, we created fractures in femurs of 6-week-old male wild type (WT or Bgn+/0) and Bgn-deficient (Bgn-KO or Bgn-/0) mice using a custom-made standardized fracture device, and analyzed the process of healing over time. The formation of a callus around the fracture site was observed at both 7 and 14 days post-fracture in WT and Bgn-deficient mice and immunohistochemistry revealed that Bgn was highly expressed in the fracture callus of WT mice, localizing within woven bone and cartilage. Micro-computed tomography (?CT) analysis of the region surrounding the fracture line showed that the Bgn-deficient mice had a smaller callus than WT mice. Histology of the same region also showed the presence of less cartilage and woven bone in the Bgn-deficient mice compared to WT mice. Picrosirius red staining of the callus visualized under polarized light showed that there was less fibrillar collagen in the Bgn-deficient mice, a finding confirmed by immunohistochemistry using antibodies to type I collagen. Interestingly, real time RT-PCR of the callus at 7 days post-fracture showed a significant decrease in relative vascular endothelial growth factor A (VEGF) gene expression by Bgn-deficient mice as compared to WT. Moreover, VEGF was shown to bind directly to Bgn through a solid-phase binding assay. The inability of Bgn to directly enhance VEGF-induced signaling suggests that Bgn has a unique role in regulating vessel formation, potentially related to VEGF storage or stabilization in the matrix. Taken together, these results suggest that Bgn has a regulatory role in the process of bone formation during fracture healing, and further, that reduced angiogenesis could be the molecular basis. PMID:24373744

Berendsen, Agnes D; Pinnow, Emily L; Maeda, Azusa; Brown, Aaron C; McCartney-Francis, Nancy; Kram, Vardit; Owens, Rick T; Robey, Pamela G; Holmbeck, Kenn; de Castro, Luis F; Kilts, Tina M; Young, Marian F

2014-04-01

96

Identification of Mechanosensitive Genes during Embryonic Bone Formation  

PubMed Central

Although it is known that mechanical forces are needed for normal bone development, the current understanding of how biophysical stimuli are interpreted by and integrated with genetic regulatory mechanisms is limited. Mechanical forces are thought to be mediated in cells by “mechanosensitive” genes, but it is a challenge to demonstrate that the genetic regulation of the biological system is dependant on particular mechanical forces in vivo. We propose a new means of selecting candidate mechanosensitive genes by comparing in vivo gene expression patterns with patterns of biophysical stimuli, computed using finite element analysis. In this study, finite element analyses of the avian embryonic limb were performed using anatomically realistic rudiment and muscle morphologies, and patterns of biophysical stimuli were compared with the expression patterns of four candidate mechanosensitive genes integral to bone development. The expression patterns of two genes, Collagen X (ColX) and Indian hedgehog (Ihh), were shown to colocalise with biophysical stimuli induced by embryonic muscle contractions, identifying them as potentially being involved in the mechanoregulation of bone formation. An altered mechanical environment was induced in the embryonic chick, where a neuromuscular blocking agent was administered in ovo to modify skeletal muscle contractions. Finite element analyses predicted dramatic changes in levels and patterns of biophysical stimuli, and a number of immobilised specimens exhibited differences in ColX and Ihh expression. The results obtained indicate that computationally derived patterns of biophysical stimuli can be used to inform a directed search for genes that may play a mechanoregulatory role in particular in vivo events or processes. Furthermore, the experimental data demonstrate that ColX and Ihh are involved in mechanoregulatory pathways and may be key mediators in translating information from the mechanical environment to the molecular regulation of bone formation in the embryo. PMID:19112485

Nowlan, Niamh C.; Prendergast, Patrick J.; Murphy, Paula

2008-01-01

97

Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus  

USGS Publications Warehouse

Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.

Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

2003-01-01

98

The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate  

PubMed Central

Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagle dog model to investigate BMSC homing via blood circulation to participate in ectopic bone formation via osteoinductive biomaterial. BMSCs of male dogs were injected into female femoral marrow cavity. The survival and stable chimerism of donor BMSCs in recipients were confirmed with polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). Biphasic calcium phosphate (BCP) granules were implanted in dorsal muscles of female dogs. Y chromosomes were detected in samples harvested from female dogs which had received male BMSCs. At 4 weeks, cells with Y-chromosomes were distributed in the new bone matrix throughout the BCP granule implant. At 6 weeks, cells with Y chromosomes were present in newly mineralized woven bone. TRAP positive osteoclast-like cells were observed in 4-week implants, and the number of such cells decreased from 4 to 6 weeks. These results show that osteoprogenitors were recruited from bone marrow and homed to ectopic site to serve as a cell source for calcium phosphate-induced bone formation. In conclusion, BMSCs were demonstrated to migrate from bone marrow through blood circulation to non-osseous bioceramic implant site to contribute to ectopic bone formation in a canine model. BCP induced new bone in muscles without growth factor delivery, showing excellent osteoinductivity that could be useful for bone tissue engineering. PMID:23298780

Song, Guodong; Habibovic, Pamela; Bao, Chongyun; Hu, Jing; van Blitterswijk, Clemens A.; Yuan, Huipin; Chen, Wenchuan; Xu, Hockin H.K.

2013-01-01

99

Putative Function of TAP63? during Endochondral Bone Formation  

PubMed Central

P63, a member of the P53 tumor suppressor family, is known to play important functions in cancer and development. Interestingly, previous studies have shown that p63 null mice are absent or have truncated limbs, while mutations in human P63 cause several skeletal syndromes that also show limb and digit abnormalities, suggesting its essential role in long bone development. Indeed, we detected increased level of p63 transcript in hypertrophic MCT cells (an established cell model of chondrocyte maturation) than in proliferative MCT cells. To investigate the in vivo role of P63 upon endochondral bone formation, we have established transgenic mouse lines in which HA- and Flag-tagged TAP63? (the longest P63 isoform) is driven by the hypertrophic chondrocyte-specific Col10a1 regulatory elements. Skeletal staining of Col10a1-TAP63? transgenic mice at either embryonic day 17.5 (E17.5) or postnatal day 1 (P1) observed accelerated ossification in long bone, digit and tail bones compared to their wild-type littermates, suggesting a putative function of P63 during skeletal development. We also detected decreased level of Sox9 and Bcl-2 transcripts, while Alp and Ank are slightly upregulated in Col10a1-TAP63? transgenic mouse limbs. Further immunohistochemical analysis confirmed the decreased Sox9 expression in the proliferative and hypertrophic zone of these mice. Von Kossa staining suggests increased mineralization in hypertrophic zone of transgenic mice compared to littermate controls. Together, our results suggest a role of TAP63? upon skeletal development. TAP63a may promote endochondral ossification through interaction with genes relevant to matrix mineralization and chondrocyte maturation or apoptosis PMID:22244744

Li, Feifei; Lu, Yaojuan; Ding, Ming; Wu, Guojun; Sinha, Satrajit; Wang, Siying; Zheng, Qiping

2012-01-01

100

Impaired Bone Formation in Pdia3 Deficient Mice  

PubMed Central

1?,25-dihydroxyvitamin D3 [1?,25(OH)2D3] is crucial for normal skeletal development and bone homeostasis. Protein disulfide isomerase family A, member 3 (PDIA3) mediates 1?,25(OH)2D3 initiated-rapid membrane signaling in several cell types. To understand its role in regulating skeletal development, we generated Pdia3-deficient mice and examined the physiologic consequence of Pdia3-disruption in embryos and Pdia3+/? heterozygotes at different ages. No mice homozygous for the Pdia3-deletion were found at birth nor were there embryos after E12.5, indicating that targeted disruption of the Pdia3 gene resulted in early embryonic lethality. Pdia3-deficiency also resulted in skeletal manifestations as revealed by µCT analysis of the tibias. In comparison to wild type mice, Pdia3 heterozygous mice displayed expanded growth plates associated with decreased tether formation. Histomorphometry also showed that the hypertrophic zone in Pdia3+/? mice was more cellular than seen in wild type growth plates. Metaphyseal trabecular bone in Pdia3+/? mice exhibited an age-dependent phenotype with lower BV/TV and trabecular numbers, which was most pronounced at 15 weeks of age. Bone marrow cells from Pdia3+/? mice exhibited impaired osteoblastic differentiation, based on reduced expression of osteoblast markers and mineral deposition compared to cells from wild type animals. Collectively, our findings provide in vivo evidence that PDIA3 is essential for normal skeletal development. The fact that the Pdia3+/? heterozygous mice share a similar growth plate and bone phenotype to nVdr knockout mice, suggests that PDIA3-mediated rapid membrane signaling might be an alternative mechanism responsible for 1?,25(OH)2D3’s actions in regulating skeletal development. PMID:25405762

Wang, Yun; Nizkorodov, Alexandr; Riemenschneider, Kelsie; Lee, Christopher S. D.; Olivares-Navarrete, Rene; Schwartz, Zvi; Boyan, Barbara D.

2014-01-01

101

NF-?B RelB negatively regulates osteoblast differentiation and bone formation.  

PubMed

RelA-mediated NF-?B canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-?B RelB may also negatively regulate bone formation through noncanonical signaling, but they involved a complex knockout mouse model, and the molecular mechanisms involved were not investigated. Here, we report that RelB(-/-) mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB(-/-) bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runt-related transcription factor 2 (Runx2). In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB(-/-) bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair. PMID:24115294

Yao, Zhenqiang; Li, Yanyun; Yin, Xiaoxiang; Dong, Yufeng; Xing, Lianping; Boyce, Brendan F

2014-04-01

102

Ibuprofen Administered Pre- or Post- Simulated Resistance Exercise Training Does Not Diminsh Gains in Bone Formation or Bone Mass  

E-print Network

Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to suppress bone formation when administered before, but not if administered after, an acute bout of mechanical load in rats. The NSAID ibuprofen inhibits cyclooxygenase-2 enzyme...

Cunningham, David

2012-02-14

103

Bone Formation and Resorption Are Both Increased in Experimental Autoimmune Arthritis  

PubMed Central

Introduction Arthritic bone loss in the joints of patients with rheumatoid arthritis is the result of a combination of osteoclastic bone resorption and osteoblastic bone formation. This process is not completely understood, and especially the importance of local inflammation needs further investigation. We evaluated how bone formation and bone resorption are altered in experimental autoimmune arthritis. Methods Twenty-one female SKG mice were randomized to either an arthritis group or a control group. Tetracycline was used to identify mineralizing surfaces. After six weeks the right hind paws were embedded undecalcified in methylmethacrylate. The paws were cut exhaustively according to the principles of vertical sectioning and systematic sampling. 3D design-based methods were used to estimate the total number of osteoclasts, mineralizing surfaces, eroded surfaces, and osteoclast-covered bone surfaces. In addition the presence of adjacent inflammation was ascertained. Results The total number of osteoclasts, mineralizing surfaces, eroded surfaces, and osteoclast covered surfaces were elevated in arthritic paws compared to normal paws. Mineralizing surfaces were elevated adjacent to as well as not adjacent to inflammation in arthritic mice compared to normal mice. In arthritic mice, eroded surfaces and osteoclast covered surfaces were larger on bone surfaces adjacent to inflammation than on bone surfaces without adjacent inflammation. However, we found no difference between mineralizing surfaces at bone surfaces with or without inflammation in arthritic mice. Conclusions Inflammation induced an increase in resorptive bone surfaces as well as formative bone surfaces. The bone formative response may be more general, since formative bone surfaces were also increased when not associated with inflammation. Thus, the bone loss may be the result of a substantial local bone resorption, which cannot be compensated by the increased local bone formation. These findings may be valuable for the development of new osteoblast targeting drugs in RA. PMID:23300855

Keller, Kresten Krarup; Thomsen, Jesper Skovhus; Stengaard-Pedersen, Kristian; Dagnæs-Hansen, Frederik; Nyengaard, Jens Randel; Hauge, Ellen-Margrethe

2012-01-01

104

Bone Formation in a Rat Tibial Defect Model Using Carboxymethyl Cellulose/BioC/Bone Morphogenic Protein-2 Hybrid Materials  

PubMed Central

The objective of this study was to assess whether carboxymethyl cellulose- (CMC-) based hydrogel containing BioC (biphasic calcium phosphate (BCP); tricalcium phosphate (TCP)?:?hydroxyapatite (Hap) = 70?:?30) and bone morphogenic protein-2 (BMP-2) led to greater bone formation than CMC-based hydrogel containing BioC without BMP-2. In order to demonstrate bone formation at 4 and 8 weeks, plain radiographs, microcomputed tomography (micro-CT) evaluation, and histological studies were performed after implantation of all hybrid materials on an 8?mm defect of the right tibia in rats. The plain radiographs and micro-CT analyses revealed that CMC/BioC/BMP-2 (0.5?mg) led to much greater mineralization at 4 and 8 weeks than did CMC/BioC or CMC/Bio/BMP-2 (0.1?mg). Likewise, bone formation and bone remodeling studies revealed that CMC/BioC/BMP-2 (0.5?mg) led to a significantly greater amount of bone formation and bone remodeling at 4 and 8 weeks than did CMC/BioC or CMC/BioC/BMP-2 (0.1?mg). Histological studies revealed that mineralized bone tissue was present around the whole circumference of the defect site with CMC/BioC/BMP-2 (0.5?mg) but not with CMC/BioC or CMC/BioC/BMP-2 (0.1?mg) at 4 and 8 weeks. These results suggest that CMC/BioC/BMP-2 hybrid materials induced greater bone formation than CMC/BioC hybrid materials. Thus, CMC/BioC/BMP-2 hybrid materials may be used as an injectable substrate to regenerate bone defects. PMID:24804202

Kim, Hak-Jun; Park, Kyeongsoon; Kim, Sung Eun; Song, Hae-Ryong

2014-01-01

105

New bone formation in nude mouse calvaria induced by canine prostate tissue.  

PubMed

Osteoblastic metastases are common in patients with advanced prostate cancer. The pathophysiology of the new bone formation at metastatic sites is not currently known, but it is hypothesized that growth factors secreted by the prostate may be involved. Unfortunately, most rodent models of prostate cancer with metastasis to bone are osteolytic and not osteoblastic. Significant osteolysis by tumor cells at metastatic sites also may lead to fractures or bone instability. Misinterpretation of new periosteal bone due to bone instability as tumor-cell osteo-induction is another disadvantage of the osteolytic models. To circumvent these problems, we have developed a model system of new bone formation in the calvaria of nude mice stimulated by normal canine prostate tissue. Collagenase-digested normal prostate tissue was implanted adjacent to the calvaria of nude mice. Calvaria were examined at 2 weeks post-implantation for changes in the bone microenvironment by histology, calcein uptake at sites of bone mineralization, and tartrate-resistant acid phosphatase staining for osteoclasts. The prostate tissue remained viable and induced abundant new woven bone formation on the adjacent periosteal surface. In some cases new bone formation also was induced on the distant or concave calvarial periosteum. The new bone stained intensely with calcein, which demonstrated mineralization of the bone matrix. The new bone formation on prostate-implanted calvaria significantly increased (1.7-fold) the thickness of the calvaria compared with control calvaria. New bone formation was not induced in calvaria of mice implanted with normal canine kidney, urinary bladder, spleen, or skeletal muscle tissue, or mice with surgically-induced disruption of the periosteum. Osteoclast numbers in the medullary spaces and periosteum of calvaria were mildly increased (61%) in mice with implanted prostate tissue. In conclusion, this animal model will be useful for investigating the roles of prostate-derived growth factors on new bone formation in vivo. PMID:12431820

LeRoy, Bruce E; Bahnson, Robert R; Rosol, Thomas J

2002-11-29

106

Ursolic acid incorporation does not prevent the formation of a non-lamellar phase in pH-sensitive and long-circulating liposomes.  

PubMed

Ursolic acid (UA) is a triterpene found in different plant species that has been shown to possess significant antitumor activity. However, UA presents a low water solubility, which limits its biological applications. In this context, our research group has proposed the incorporation of UA in long-circulating and pH-sensitive liposomes (SpHL-UA).These liposomes, composed of dioleylphosphatidylethanolamine (DOPE), cholesteryl hemisuccinate (CHEMS), and distearoylphosphatidylethanolamine-polyethylene glycol2000 (DSPE-PEG2000), were shown to be very promising carriers for UA. Considering that the release of UA from SpHL-UA and its antitumor activity depend upon the occurrence of the lamellar to non-lamellar phase transition of DOPE, in the present work, the interactions of UA with the components of the liposomes were evaluated, aiming to clarify their role in the structural organization of DOPE. The study was carried out by differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) under low hydration conditions. DSC studies revealed that DOPE phase transition temperatures did not shift significantly upon UA addition. On the other hand, in SAXS studies, a different pattern of DOPE phase organization was observed in the presence of UA, with the occurrence of the cubic phase Im3m at 20 °C and the cubic phase Pn3m at 60 °C. These findings suggest that UA interacts with the lipids and changes their self-assembly. However, these interactions between the lipids and UA were unable to eliminate the lamellar to non-lamellar phase transition, which is essential for the cytoplasmic delivery of UA molecules from SpHL-UA. PMID:25490253

Lopes, Sávia C A; Novais, Marcus V M; Ferreira, Diêgo S; Braga, Fernão C; Magalhães-Paniago, Rogério; Malachias, Ângelo; Oliveira, Mônica C

2014-12-23

107

The effect of bovine whey protein on ectopic bone formation in young growing rats  

Microsoft Academic Search

The beneficial effect of bovine whey protein (WP) on bone metabolism has been shown in adult human subjects and ovariectomised rats. However, its effect on bone formation in earlier life, particularly during periods of bone mineral accrual, has not been investigated. Twenty-one male rats (4 weeks old, Wistar strain) were randomised by weight into three groups of seven rats each

Owen Kelly; Siobhan Cusack; Kevin D. Cashman

2003-01-01

108

Controlled delivery of platelet-rich plasma-derived growth factors for bone formation  

E-print Network

. Orthopedic and maxillofacial bone defects are frequently reconstructed with either auto- logous or allogeneic has been reported to improve the aggregation and cohesiveness of partic- ulate-based bone substitutesControlled delivery of platelet-rich plasma-derived growth factors for bone formation Helen H. Lu,1

Lu, Helen H.

109

Wnt signaling in bone formation and its therapeutic potential for bone diseases  

PubMed Central

The Wnt signaling pathway plays an important role not only in embryonic development but also in the maintenance and differentiation of the stem cells in adulthood. In particular, Wnt signaling has been shown as an important regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. Induction of the Wnt signaling pathway promotes bone formation while inactivation of the pathway leads to osteopenic states. Our current understanding of Wnt signaling in osteogenesis elucidates the molecular mechanisms of classic osteogenic pathologies. Activating and inactivating aberrations of the canonical Wnt signaling pathway in osteogenesis results in sclerosteosis and osteoporosis respectively. Recent studies have sought to target the Wnt signaling pathway to treat osteogenic disorders. Potential therapeutic approaches attempt to stimulate the Wnt signaling pathway by upregulating the intracellular mediators of the Wnt signaling cascade and inhibiting the endogenous antagonists of the pathway. Antibodies against endogenous antagonists, such as sclerostin and dickkopf-1, have demonstrated promising results in promoting bone formation and fracture healing. Lithium, an inhibitor of glycogen synthase kinase 3?, has also been reported to stimulate osteogenesis by stabilizing ? catenin. Although manipulating the Wnt signaling pathway has abundant therapeutic potential, it requires cautious approach due to risks of tumorigenesis. The present review discusses the role of the Wnt signaling pathway in osteogenesis and examines its targeted therapeutic potential. PMID:23514963

Kim, Jeong Hwan; Liu, Xing; Wang, Jinhua; Chen, Xiang; Zhang, Hongyu; Kim, Stephanie H.; Cui, Jing; Li, Ruidong; Zhang, Wenwen; Kong, Yuhan; Zhang, Jiye; Shui, Wei; Lamplot, Joseph; Rogers, Mary Rose; Zhao, Chen; Wang, Ning; Rajan, Prashant; Tomal, Justin; Statz, Joseph; Wu, Ningning; Luu, Hue H.; Haydon, Rex C.

2013-01-01

110

Dexamethasone Enhances Osteogenic Differentiation of Bone Marrow- and Muscle-Derived Stromal Cells and Augments Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2  

PubMed Central

We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2. Highlights: 1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2. PMID:25659106

Yuasa, Masato; Yamada, Tsuyoshi; Taniyama, Takashi; Masaoka, Tomokazu; Xuetao, Wei; Yoshii, Toshitaka; Horie, Masaki; Yasuda, Hiroaki; Uemura, Toshimasa; Okawa, Atsushi; Sotome, Shinichi

2015-01-01

111

Formation of a bone apatite-like layer on the surface of porous hydroxyapatite ceramics.  

PubMed

Phosphoric acid solution was used to react with commercial hydroxyapatite (HA) powders to demonstrate the possibility of converting HA to non-stoichiometric apatite and thus to treat porous HA ceramics, to form a thin bone-apatite like layer on the HA ceramic surface. Such a carbonate-containing non-stoichiometric apatite "bioceramic" would be more efficient in bone bonding or bone formation, due to its analogy to natural bone apatite. PMID:7986949

Yubao, L; Klein, C P; Zhang, X; de Groot, K

1994-08-01

112

Computational and experimental methodology for site-matched investigations of the influence of mineral mass fraction and collagen orientation on the axial indentation modulus of lamellar bone?  

PubMed Central

Relationships between mineralization, collagen orientation and indentation modulus were investigated in bone structural units from the mid-shaft of human femora using a site-matched design. Mineral mass fraction, collagen fibril angle and indentation moduli were measured in registered anatomical sites using backscattered electron imaging, polarized light microscopy and nano-indentation, respectively. Theoretical indentation moduli were calculated with a homogenization model from the quantified mineral densities and mean collagen fibril orientations. The average indentation moduli predicted based on local mineralization and collagen fibers arrangement were not significantly different from the average measured experimentally with nanoindentation (p=0.9). Surprisingly, no substantial correlation of the measured indentation moduli with tissue mineralization and/or collagen fiber arrangement was found. Nano-porosity, micro-damage, collagen cross-links, non-collagenous proteins or other parameters affect the indentation measurements. Additional testing/simulation methods need to be considered to properly understand the variability of indentation moduli, beyond the mineralization and collagen arrangement in bone structural units. PMID:23994944

Spiesz, Ewa M.; Reisinger, Andreas G.; Kaminsky, Werner; Roschger, Paul; Pahr, Dieter H.; Zysset, Philippe K.

2013-01-01

113

Methodology developed for the simultaneous measurement of bone formation and bone resorption in rats based on the pharmacokinetics of fluoride.  

PubMed

This paper describes a novel methodology for the simultaneous estimation of bone formation (BF) and resorption (BR) in rats using fluoride as a nonradioactive bone-seeker ion. The pharmacokinetics of flouride have been extensively studied in rats; its constants have all been characterized. This knowledge was the cornerstone for the underlying mathematical model that we used to measure bone fluoride uptake and elimination rate after a dose of fluoride. Bone resorption and formation were estimated by bone fluoride uptake and elimination rate, respectively. ROC analysis showed that sensitivity, specificity and area under the ROC curve were not different from deoxypiridinoline and bone alkaline phosphatase, well-known bone markers. Sprague-Dawley rats with modified bone remodelling (ovariectomy, hyper, and hypocalcic diet, antiresorptive treatment) were used to validate the values obtained with this methodology. The results of BF and BR obtained with this technique were as expected for each biological model. Although the method should be performed under general anesthesia, it has several advantages: simultaneous measurement of BR and BF, low cost, and the use of compounds with no expiration date. PMID:24445963

Lupo, Maela; Brance, Maria Lorena; Fina, Brenda Lorena; Brun, Lucas Ricardo; Rigalli, Alfredo

2015-01-01

114

Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss  

PubMed Central

Targeted disruption of the histidine decarboxylase gene (HDC?/?), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC?/? mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC?/? mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1?-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-?B ligand concentrations, and suppressed parathyroid hormone concentrations in HDC?/? mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption. PMID:12716972

Fitzpatrick, L. A.; Buzas, E.; Gagne, T. J.; Nagy, A.; Horvath, C.; Ferencz, V.; Mester, A.; Kari, B.; Ruan, M.; Falus, A.; Barsony, J.

2003-01-01

115

Decreased bone area, bone mineral content, formative markers, and increased bone resorptive markers in endogenous Cushing's syndrome  

Microsoft Academic Search

It is well established that chronic excess of glucocorticoids has negative effects on bone and collagen turnover, and that secondary osteoporosis is a known clinical complication of endogenous Cushing's syndrome (CS). The aim of the present study was to evaluate bone dimension and bone mineral content in relation to biochemical markers of bone and collagen turnover, in a consecutive series

Kristin Godang; Thor Ueland; Jens Bollerslev

1999-01-01

116

The use of bovine screws to promote bone formation using a tibia model in dogs  

PubMed Central

The objective of this study was to evaluate the use of a unique resorbable bovine bone screw, to stimulate bone formation. Bovine bone screws were inserted in the tibia beagle dogs. Each animal received 8 screws, divided into Groups A (screws + no membranes), B (screws + titanium reinforced membranes) and C (bone defects treated with autogenous bone grafts). Animals were sacrificed at 2, 4 and 6 months. New bone was measured with a periodontal probe and reported an average of 7.4 mm in vertical bone gain for Group B, 3.6 mm for Group A and 1.7 mm for Group C. Submission to Kruskal-Wallis test showed statistical differences between groups (p<0,05). Histological examination revealed an intimate contact between the newly formed bone and the resorbing bone screws. Conclusion: Bovine bone screws provide environment for new bone formation and thus may provide an alternative therapy for enhancing bone formation vertically, including for regenerative procedures as well as prior to implant therapy. PMID:23058228

Bianchini, Marco Aurélio; Pontual, Marco Antônio B; Bez, Leonardo; Benfatti, César Augusto M; Boabaid, Fernanda; Somerman, Martha J; Magini, Ricardo S

2013-01-01

117

Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats  

NASA Technical Reports Server (NTRS)

Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that programed administration of PTH is effective in increasing osteoblast number and bone formation and has beneficial effects on bone volume in the absence of weight-bearing and gonadal hormones. We conclude that the actions of PTH on cancellous bone are independent of the level of mechanical usage.

Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

1998-01-01

118

Effect of the combination of enamel matrix derivatives and deproteinized bovine bone materials on bone formation in rabbits’ calvarial defects  

PubMed Central

Background: Various types of materials are used in bone regeneration procedures. The aim of this study was to investigate the use of the enamel matrix derivative (EMD), deproteinized bovine bone mineral (Bio-Oss), and a combination of Bio-Oss plus EMD in the treatment of bone defects created in the rabbits’ calvaria. Materials and Methods: Twenty New Zealand white rabbits were included in this experimental randomized single blind study. Four equal cranial bone defects (3 × 6 × 0.5 mm3) were created in frontal and parietal bone and randomly grafted with Bio-Oss (Group 1), EMD (Group 2), EMD + Bio-Oss (Group 3) and one of them was left unfilled to serve as a control group (Group 4). After 2, 4, 8, and 12 weeks the defects were evaluated by using histological and histomorphometric analysis. Data were analyzed by the Bonferroni test using SPSS 13 statistical software. P value <0.05 considered as statistically significant level. Results: Bone formation in the EMD + Bio-Oss group after 2 weeks was diminished when statistically compared to the other groups (P < 0.05). Bone augmentation after 4 weeks from the lowest to the highest were found in groups 1, 3, 2, and 4, respectively, and these differences were statistically significant (P < 0.05). Using EMD with Bio-Oss increased bone formation in the non-critical defects in the rabbit calvaria during 8 and 12 weeks (P < 0.05). Conclusions: Boosting of EMD plus Bio-Oss seems to have synergic effect on bone regeneration in bone defects. PMID:23162582

Shahriari, Shahriar; Houshmand, Behzad; Razavian, Hamid; Khazaei, Saber; Abbas, Fatemeh Mashhadi

2012-01-01

119

Radiostrontium clearance and bone formation in response to simulated internal screw fixation  

SciTech Connect

Changes in radiostrontium clearance (SrC) and bone formation (tetracycline labeling) were observed in the femurs of skeletally mature dogs following the various operative steps involved in bone screw fixation. Drilling, but not periosteal stripping, produced a small but statistically significant increase in SrC and endosteal bone formation in the distal third of the bone. Strontium clearance values equivalent to those produced by drilling alone were recorded after screw fixation at low or high torque (5 versus 20 inch pounds), as well as by the insertion of loosely fitting stainless steel implants. Bone formation (equals the percentage tetracycline-labeled trabecular bone surfaces) was increased by 30% when SrC values exceeded 3.5 ml/100 g bone/min, and the relationship was linear when SrC values ranged between 1.0 and 7.0 ml/100 g bone/min. The changes in SrC and bone formation one-week after bone screw application are primarily those associated with a response to local trauma caused by drilling.

Daum, W.J.; Simmons, D.J.; Fenster, R.; Shively, R.A.

1987-06-01

120

A soluble activin type IIA receptor induces bone formation and improves skeletal integrity  

PubMed Central

Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-? superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-? signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism. Here we demonstrate that pharmacological blockade of ligand signaling through the high affinity receptor for activin, type II activin receptor (ActRIIA), by administration of the soluble extracellular domain of ActRIIA fused to a murine IgG2a-Fc, increases bone formation, bone mass, and bone strength in normal mice and in ovariectomized mice with established bone loss. These observations support the development of this pharmacological strategy for the treatment of diseases with skeletal fragility. PMID:18460605

Pearsall, R. Scott; Canalis, Ernesto; Cornwall-Brady, Milton; Underwood, Kathryn W.; Haigis, Brendan; Ucran, Jeffrey; Kumar, Ravindra; Pobre, Eileen; Grinberg, Asya; Werner, Eric D.; Glatt, Vaida; Stadmeyer, Lisa; Smith, Deanna; Seehra, Jasbir; Bouxsein, Mary L.

2008-01-01

121

Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles.  

PubMed

The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation, balanced by its degradation. Therefore, we set out to engineer endochondral bone in gelatin methacrylamide (GelMA) hydrogels with embedded multipotent stromal cells (MSCs) and cartilage-derived matrix (CDM) particles. CDM particles were found to stimulate the formation of a cartilage template by MSCs in the GelMA hydrogel in vitro. In a subcutaneous rat model, this template was subsequently remodeled into mineralized bone tissue, including bone-marrow cavities. The GelMA was almost fully degraded during this process. There was no significant difference in the degree of calcification in GelMA with or without CDM particles: 42.5 ± 2.5% vs. 39.5 ± 8.3% (mean ± standard deviation), respectively. Interestingly, in an osteochondral setting, the presence of chondrocytes in one half of the constructs fully impeded bone formation in the other half by MSCs. This work offers a new avenue for the engineering of relevant-size bone grafts, by the formation of endochondral bone within a degradable hydrogel. PMID:25453948

Visser, Jetze; Gawlitta, Debby; Benders, Kim E M; Toma, Selynda M H; Pouran, Behdad; van Weeren, P René; Dhert, Wouter J A; Malda, Jos

2015-01-01

122

Prostaglandin E2 Prevents Bone Loss and Adds Extra Bone to Immobilized Distal Femoral Metaphysis in Female Rats  

NASA Technical Reports Server (NTRS)

The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloading)-induced cancellous bone loss. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to right hindlimb immobilization by bandaging and simultaneously treated subcutaneously daily with 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on the cancellous bone using double-fluorescent labeled, 20 micron thick, undecalcified distal femoral metaphysis sections. We found that PGE2 administration not only prevented disuse-induced bone loss, but also added extra bone to disuse cancellous bone in a dose-response manner. PGE2 prevented the disuse-induced osteopenia by stimulating more bone formation than and shortening the period of bone remodeling. It activated woven bone formation, stimulated lamellar bone formation, and increased the eroded bone surface above that caused by disuse alone. While underloading increased the remodeling period (sigma), PGE2 treatment of underloaded bone shortened the time for osteoclastic bone resorption and bone remodeling, and thus reduced the remodeling space. The study shows that PGE2 is a powerful anabolic agent that prevents disuse-induced osteopenia and adds extra bone to these same bones.

Akamine, T.; Jee, W. S. S.; Ke, H. Z.; Li, X. J.; Lin, B. Y.

1992-01-01

123

The effect of diabetes mellitus on rat mandibular bone formation and microarchitecture.  

PubMed

The aim of this study was to assess the effect of type 1 diabetes mellitus (DM) on the structure of mandibular bone and on the changes of alveolar/jaw bone formation. Experimental DM was induced in 3-wk-old male Wistar rats by a single dose of 60 mg/kg body weight of streptozotocin. All rats were injected with calcein on days 21 and 28. The rats were killed when 8 wk of age. Bone structure was analyzed by bone histomorphometry, microcomputed tomography (micro-CT), and histological section. Histomorphometric analysis showed that the mineral apposition and the bone formation rates in most of the mandibular regions were significantly decreased in the DM group compared with the control group. Micro-CT analysis showed significant deterioration of the bone quality in rats with DM. For a histometric measure of bone resorption, the number of osteoclasts along the distal surface of the alveolar wall was counted. The number of osteoclasts was significantly lower in the rats with DM than in the controls. These findings suggest that uncontrolled DM decreases mandibular bone formation, reduces the rate of bone turnover in the alveolar wall surrounding the root, and affects the quality of bone structure resulting in retardation of its skeletal development. PMID:20662909

Abbassy, Mona A; Watari, Ippei; Soma, Kunimichi

2010-08-01

124

Impact of skeletal unloading on bone formation: Role of systemic and local factors  

NASA Astrophysics Data System (ADS)

We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

125

Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation  

PubMed Central

Bone remodeling is characterized by the sequential, local tethering of osteoclasts and osteoblasts and is key to the maintenance of bone integrity. While bone matrix–mobilized growth factors, such as TGF-?, are proposed to regulate remodeling, no in vivo evidence exists that an osteoclast-produced molecule serves as a coupling factor for bone resorption to formation. We found that CTHRC1, a protein secreted by mature bone-resorbing osteoclasts, targets stromal cells to stimulate osteogenesis. Cthrc1 expression was robustly induced when mature osteoclasts were placed on dentin or hydroxyapatite, and also by increasing extracellular calcium. Cthrc1 expression in bone increased in a high-turnover state (such as that induced by RANKL injections in vivo), but decreased in conditions associated with suppressed bone turnover (such as with aging and after alendronate treatment). Targeted deletion of Cthrc1 in mice eliminated Cthrc1 expression in bone, whereas its deficiency in osteoblasts did not exert any significant effect. Osteoclast-specific deletion of Cthrc1 resulted in osteopenia due to reduced bone formation and impaired the coupling process after resorption induced by RANKL injections, impairing bone mass recovery. These data demonstrate that CTHRC1 is an osteoclast-secreted coupling factor that regulates bone remodeling. PMID:23908115

Takeshita, Sunao; Fumoto, Toshio; Matsuoka, Kazuhiko; Park, Kyoung-ae; Aburatani, Hiroyuki; Kato, Shigeaki; Ito, Masako; Ikeda, Kyoji

2013-01-01

126

Chondrocyte ?-Catenin Signaling Regulates Postnatal Bone Remodeling Through Modulation of Osteoclast Formation in a Murine Model  

PubMed Central

Objective To investigate whether ?-catenin signaling in chondrocytes regulates osteoclastogenesis, thereby contributing to postnatal bone growth and bone remodeling. Methods Mice with conditional knockout (cKO) or conditional activation (cAct) of chondrocyte-specific ?-catenin were generated. Changes in bone mass, osteoclast numbers, and osteoblast activity were examined. The mechanisms by which ?-catenin signaling in chondrocytes regulates osteoclast formation were determined. Results The ?-catenin cKO mice developed localized bone loss, whereas cAct mice developed a high bone mass phenotype. Histologic findings suggested that these phenotypes were caused primarily by impaired osteoclast formation, rather than impaired bone formation. Further molecular signaling analyses revealed that ?-catenin signaling controlled this process by regulating the expression of the RANKL and osteoprotegerin (OPG) genes in chondrocytes. Activation of ?-catenin signaling in chondrocytes suppressed Rankl gene transcription through a glucocorticoid receptor–dependent mechanism. The severe bone loss phenotype observed in ?-catenin cKO mice was largely restored by treatment with human recombinant OPG or transgenic overexpression of Opg in chondrocytes. Conclusion ?-catenin signaling in chondrocytes plays a key role in postnatal bone growth and bone remodeling through its regulation of osteoclast formation. PMID:24431282

Wang, Baoli; Jin, Hongting; Zhu, Mei; Li, Jia; Zhao, Lan; Zhang, Yejia; Tang, Dezhi; Xiao, Guozhi; Xing, Lianping; Boyce, Brendan F.; Chen, Di

2014-01-01

127

Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone  

PubMed Central

Background & objectives: Various materials have been used as scaffolds to suit different demands in tissue engineering. One of the most important criteria is that the scaffold must be biocompatible. This study was carried out to investigate the potential of HA or TCP/HA scaffold seeded with osteogenic induced sheep marrow cells (SMCs) for bone tissue engineering. Methods: HA-SMC and TCP/HA-SMC constructs were induced in the osteogenic medium for three weeks prior to implantation in nude mice. The HA-SMC and TCP/HA-SMC constructs were implanted subcutaneously on the dorsum of nude mice on each side of the midline. These constructs were harvested after 8 wk of implantation. Constructs before and after implantation were analyzed through histological staining, scanning electron microscope (SEM) and gene expression analysis. Results: The HA-SMC constructs demonstrated minimal bone formation. TCP/HA-SMC construct showed bone formation eight weeks after implantation. The bone formation started on the surface of the ceramic and proceeded to the centre of the pores. H&E and Alizarin Red staining demonstrated new bone tissue. Gene expression of collagen type 1 increased significantly for both constructs, but more superior for TCP/HA-SMC. SEM results showed the formation of thick collagen fibers encapsulating TCP/HA-SMC more than HA-SMC. Cells attached to both constructs surface proliferated and secreted collagen fibers. Interpretation & conclusions: The findings suggest that TCP/HA-SMC constructs with better osteogenic potential compared to HA-SMC constructs can be a potential candidate for the formation of tissue engineered bone. PMID:23852290

Sulaiman, Shamsul Bin; Keong, Tan Kok; Cheng, Chen Hui; Saim, Aminuddin Bin; Idrus, Ruszymah Bt. Hj

2013-01-01

128

Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis.  

PubMed

Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears (Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured the serum concentrations of hormones and growth factors involved in bone metabolism and correlated them with the serum concentration of a bone formation marker (osteocalcin). Serum was obtained from black bears over a 7-month duration that included periods of activity and inactivity. Both resorption and formation markers increased during hibernation, suggesting high bone turnover occurred during inactivity. However, bone formation appeared to be balanced with bone resorption. The serum concentration of parathyroid hormone (PTH) was higher in the hibernation (P=0.35) and post-hibernation (P=0.006) seasons relative to pre-hibernation levels. Serum leptin was lower (P<0.004) post-hibernation relative to pre-hibernation and hibernation periods. Insulin-like growth factor I (IGF-I) decreased (P<0.0001) during hibernation relative to pre-hibernation and reached its highest value during remobilization. There was no difference (P=0.64) in 25-OH vitamin D between the three seasons. Serum osteocalcin (bone formation marker) was significantly correlated with PTH, but not with leptin, IGF-I or 25-OH vitamin D. Osteocalcin and PTH were positively correlated when samples from all seasons were pooled and when only hibernation samples were considered, raising the possibility that the anabolic actions of PTH help maintain bone formation to prevent disuse osteoporosis. Prostaglandin E(2) (PGE(2)) release from MC3T3 osteoblastic cells was significantly affected by treatment with bear serum from different seasons (i.e. hibernation versus active periods). The seasonal changes in PGE(2) release showed trends similar to the seasonal changes in serum IGF-I. Since both PGE(2) and IGF-I are associated with collagenous bone formation, it is possible that seasonal changes in a circulating factor influence IGF-I levels in vivo in bears and PGE(2) release in osteoblastic cells in vitro. The significant decrease in serum leptin following arousal from hibernation may promote bone formation during remobilization, assuming there is a similar decrease in intracerebroventricular leptin. These findings support the idea that seasonal changes in the concentration of circulating molecules help regulate bone formation activity and may be important for preventing disuse osteoporosis in bears. PMID:16621944

Donahue, Seth W; Galley, Sarah A; Vaughan, Michael R; Patterson-Buckendahl, Patricia; Demers, Laurence M; Vance, Josef L; McGee, Meghan E

2006-05-01

129

FLUORIDE EFFECTS ON BONE FORMATION AND MINERALIZATION ARE INFLUENCED BY GENETICS  

PubMed Central

Introduction A variation in bone response to fluoride (F?) exposure has been attributed to genetic factors. Increasing fluoride doses (0ppm, 25ppm, 50ppm, 100ppm) for three inbred mouse strains with different susceptibilities to developing dental enamel fluorosis (A/J, a “susceptible” strain; SWR/J, an “intermediate” strain; 129P3/J, a “resistant” strain) had different effects on their cortical and trabecular bone mechanical properties. In this paper, the structural and material properties of the bone were evaluated to explain the previously observed changes in mechanical properties. Materials and Methods This study assessed the effect of increasing fluoride doses on the bone formation, microarchitecture, mineralization and microhardness of the A/J, SWR/J and 129P3/J mouse strains. Bone microarchitecture was quantified with microcomputed tomography and strut analysis. Bone formation was evaluated by static histomorphometry. Bone mineralization was quantified with backscattered electron (BSE) imaging and powder x-ray diffraction. Microhardness measurements were taken from the vertebral bodies (cortical and trabecular bone) and the cortex of the distal femur. Results Fluoride treatment had no significant effect on bone microarchitecture for any of the strains. All three strains demonstrated a significant increase in osteoid formation at the largest fluoride dose. Vertebral body trabecular bone BSE imaging revealed significantly decreased mineralization heterogeneity in the SWR/J strain at 50ppm and 100ppm F?. The trabecular and cortical bone mineralization profiles showed a non-significant shift towards higher mineralization with increasing F? dose in the three strains. Powder x-ray diffraction showed significantly smaller crystals for the 129P3/J strain, and increased crystal width with increasing F? dose for all strains. There was no effect of F? on trabecular and cortical bone microhardness. Conclusion Fluoride treatment had no significant effect on bone microarchitecture in these three strains. The increased osteoid formation and decreased mineralization heterogeneity support the theory that F? delays mineralization of new bone. The increasing crystal width with increasing F? dose confirms earlier results and correlates with most of the decreased mechanical properties. An increase in bone F? may affect the mineral-organic interfacial bonding and/or bone matrix proteins, interfering with bone crystal growth inhibition on the crystallite faces as well as bonding between the mineral and organic interface. The smaller bone crystallites of the 129P3/J (resistant) strain may indicate a stronger organic/inorganic interface, reducing crystallite growth rate and increasing interfacial mechanical strength. PMID:18755305

Mousny, M.; Omelon, S.; Wise, L.; Everett, E. T.; Dumitriu, M.; Holmyard, D. P.; Banse, X.; Devogelaer, J. P.; Grynpas, M. D

2008-01-01

130

Mechanical loading, damping, and load-driven bone formation in mouse tibiae  

PubMed Central

Mechanical loads play a pivotal role in the growth and maintenance of bone and joints. Although loading can activate anabolic genes and induce bone remodeling, damping is essential for preventing traumatic bone injury and fracture. In this study we investigated the damping capacity of bone, joint tissue, muscle, and skin using a mouse hindlimb model of enhanced loading in conjunction with finite element modeling to model bone curvature. Our hypothesis was that loads were primarily absorbed by the joints and muscle tissue, but that bone also contributed to damping through its compression and natural bending. To test this hypothesis, fresh mouse distal lower limb segments were cyclically loaded in axial compression in sequential bouts, with each subsequent bout having less surrounding tissue. A finite element model was generated to model effects of bone curvature in silico. Two damping-related parameters (phase shift angle and energy loss) were determined from the output of the loading experiments. Interestingly, the experimental results revealed that the knee joint contributed to the largest portion of the damping capacity of the limb, and bone itself accounted for approximately 38% of the total phase shift angle. Computational results showed that normal bone curvature enhanced the damping capacity of the bone by approximately 40%, and the damping effect grew at an accelerated pace as curvature was increased. Although structural curvature reduces critical loads for buckling in beam theory, evolution apparently favors maintaining curvature in the tibia. Histomorphometric analysis of the tibia revealed that in response to axial loading, bone formation was significantly enhanced in the regions that were predicted to receive a curvature-induced bending moment. These results suggest that in addition to bone’s compressive damping capacity, surrounding tissues, as well as naturally-occurring bone curvature, also contribute to mechanical damping, which may ultimately affect bone remodeling and bone quality. PMID:22878153

Dodge, Todd; Wanis, Mina; Ayoub, Ramez; Zhao, Liming; Watts, Nelson B.; Bhattacharya, Amit; Akkus, Ozan; Robling, Alexander; Yokota, Hiroki

2012-01-01

131

Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix.  

PubMed

The extracellular matrix protein Fibulin-1 (Fbln1) has been shown to be involved in numerous processes including cardiovascular and lung development. Here we have examined the role of Fbln1 in bone formation. Alizarin red staining of skulls from Fbln1-deficient mice showed reduced mineralization of both membranous and endochondral bones. MicroCT (?CT) analysis of the calvarial bones (i.e., frontal, parietal and interparietal bones collectively) indicated that bone volume in Fbln1 nulls at neonatal stage P0 were reduced by 22% (p=0.015). Similarly, Fbln1 null frontal bones showed a 16% (p=0.035) decrease in bone volume, with a reduction in the interfrontal bone, and a discontinuity in the leading edge of the frontal bone. To determine whether Fbln1 played a role in osteoblast differentiation during bone formation, qPCR was used to measure the effects of Fbln1 deficiency on the expression of Osterix (Osx), a transcription factor essential for osteoblast differentiation. This analysis demonstrated that Osx mRNA was significantly reduced in Fbln1-deficient calvarial bones at developmental stages E16.5 (p=0.049) and E17.5 (p=0.022). Furthermore, the ability of Bmp-2 to induce Osx expression was significantly diminished in Fbln1-deficient mouse embryo fibroblasts. Together, these findings indicate that Fbln1 is a new positive modulator of the formation of membranous bone and endochondral bone in the skull, acting as a positive regulator of Bmp signaling. PMID:25201465

Cooley, Marion A; Harikrishnan, Keerthi; Oppel, James A; Miler, Sloan F; Barth, Jeremy L; Haycraft, Courtney J; Reddy, Sakamuri V; Scott Argraves, W

2014-12-01

132

The effect of semelil (angipars®) on bone resorption and bone formation markers in type 2 diabetic patients  

PubMed Central

Background and purpose of the study Diabetes mellitus has been recognized as a major risk factor for osteoporosis in which bone turnover is affected by different mechanisms. As the morbidity, mortality and financial cost related to osteoporosis are expected to rise in Iran in coming years, and considering the efficacy of Angipars® for improvement of different ulcers which made it a new herbal drug in diabetic foot ulcer, there is a need to evaluate the effect of this new drug on different organs including bone resorption and bone formation markers. Methods In this randomized, double- blind clinical trial, 61 diabetic patients were included. The subjects were randomly divided into intervention and control groups. Subjects of intervention group received 100?mg of Angipars® twice a day. Laboratory tests including bone resorption and bone formation markers were performed at baseline and after 3?months. Result 31 patients in study group and 30 patients in control group finished the study. The mean age of the study population and the mean disease duration was respectively 51.8?±?6.2 and 7.5?±?4.7?years with no significant differences between intervention and control patients. No statistically significant differences between patients and controls were observed in pyridinoline, osteocalcin, urine calcium, bone alkaline phosphatase and tumor necrosis factor (TNF-?). Only urine creatinine level significantly changed between two groups after 3?month of treatment (p-value: 0.029) Conclusion In conclusion, the findings of this study indicate that Semelil (Angipars®) had no beneficial or harmful effects on bone. It might be other effects of this new component on bone turnover process which need more studies and more time to be discovered. PMID:23351359

2012-01-01

133

Experimental and Modeling Studies of the Lamellar Eutectic Growth of Mg-Al Alloy  

NASA Astrophysics Data System (ADS)

Directionally solidified samples of Mg-32.3 wt pct Al eutectic alloy were produced under an argon atmosphere in a vacuum Bridgman-type furnace to study the eutectic growth with different growth velocities. Typical features such as steady-state lamellar eutectic growth, lamellar branching at the quenching interface, and the formation of colony structures due to the impurity of the Mg-Al binary alloy were observed using a JEOL 6301F scanning electron microscope (JEOL Ltd., Tokyo, Japan). The lamellar spacing of the two eutectic phases was measured on the transverse sections of the samples. It was found that the relationship between the measured lamellar spacing and growth velocity agreed well with the prediction of the Jackson-Hunt model. Subsequent studies of Mg-Al eutectic growth were conducted using a numerical model based on the cellular automaton (CA) method. Taking account of the solute diffusion, constitutional undercooling, and curvature undercooling, modeling of steady-state lamellar eutectic growth was achieved. A systematic investigation of the eutectic growth morphology and lamellar spacing of the Mg-Al eutectic was carried out under directional solidification with different undercoolings, initial lamellar spacings, temperature gradients, and growth velocities. The results showed that under the interaction between solute diffusion and surface energy, the adjustment of eutectic lamellar spacing was accomplished by nucleation, lamellar branching, lamellar termination, and overgrowth. The simulated results were consistent with both the experimental results and the Jackson-Hunt eutectic theory.

Xiong, Shou-Mei; Wu, Meng-Wu

2012-01-01

134

Joint Loading Modality: Its Application to Bone Formation and Fracture Healing  

PubMed Central

Sports related injuries such as impact and stress fractures often require a rehabilitation program to stimulate bone formation and accelerate fracture healing. This review introduces a recently developed joint loading modality and evaluates its potential applications to bone formation and fracture healing in post-injury rehabilitation. Bone is a dynamic tissue whose structure is constantly altered in response to its mechanical environments. Indeed, many loading modalities can influence the bone remodeling process. The joint loading modality is, however, able to enhance anabolic responses and accelerate wound healing without inducing significant in situ strain at the site of bone formation or fracture healing. This review highlights the unique features of this loading modality and discusses its potential underlying mechanisms as well as possible clinical applications. PMID:18048437

Zhang, Ping; Malacinski, George M.; Yokota, Hiroki

2010-01-01

135

Local Mechanical Stimuli Regulate Bone Formation and Resorption in Mice at the Tissue Level  

PubMed Central

Bone is able to react to changing mechanical demands by adapting its internal microstructure through bone forming and resorbing cells. This process is called bone modeling and remodeling. It is evident that changes in mechanical demands at the organ level must be interpreted at the tissue level where bone (re)modeling takes place. Although assumed for a long time, the relationship between the locations of bone formation and resorption and the local mechanical environment is still under debate. The lack of suitable imaging modalities for measuring bone formation and resorption in vivo has made it difficult to assess the mechanoregulation of bone three-dimensionally by experiment. Using in vivo micro-computed tomography and high resolution finite element analysis in living mice, we show that bone formation most likely occurs at sites of high local mechanical strain (p<0.0001) and resorption at sites of low local mechanical strain (p<0.0001). Furthermore, the probability of bone resorption decreases exponentially with increasing mechanical stimulus (R2?=?0.99) whereas the probability of bone formation follows an exponential growth function to a maximum value (R2?=?0.99). Moreover, resorption is more strictly controlled than formation in loaded animals, and ovariectomy increases the amount of non-targeted resorption. Our experimental assessment of mechanoregulation at the tissue level does not show any evidence of a lazy zone and suggests that around 80% of all (re)modeling can be linked to the mechanical micro-environment. These findings disclose how mechanical stimuli at the tissue level contribute to the regulation of bone adaptation at the organ level. PMID:23637993

Schulte, Friederike A.; Ruffoni, Davide; Lambers, Floor M.; Christen, David; Webster, Duncan J.; Kuhn, Gisela; Müller, Ralph

2013-01-01

136

Load Regulates Bone Formation and Sclerostin Expression through a TGF?-Dependent Mechanism  

PubMed Central

Bone continually adapts to meet changing physical and biological demands. Osteoblasts, osteoclasts, and osteocytes cooperate to integrate these physical and biochemical cues to maintain bone homeostasis. Although TGF? acts on all three of these cell types to maintain bone homeostasis, the extent to which it participates in the adaptation of bone to mechanical load is unknown. Here, we investigated the role of the TGF? pathway in load-induced bone formation and the regulation of Sclerostin, a mechanosensitive antagonist of bone anabolism. We found that mechanical load rapidly represses the net activity of the TGF? pathway in osteocytes, resulting in reduced phosphorylation and activity of key downstream effectors, Smad2 and Smad3. Loss of TGF? sensitivity compromises the anabolic response of bone to mechanical load, demonstrating that the mechanosensitive regulation of TGF? signaling is essential for load-induced bone formation. Furthermore, sensitivity to TGF? is required for the mechanosensitive regulation of Sclerostin, which is induced by TGF? in a Smad3-dependent manner. Together, our results show that physical cues maintain bone homeostasis through the TGF? pathway to regulate Sclerostin expression and the deposition of new bone. PMID:23308287

Nguyen, Daniel; Alliston, Tamara

2013-01-01

137

Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles.  

PubMed

Calcium phosphate ceramics are widely used in bone reconstructive surgery because of their osteconductive properties. However, these materials generally lack osteoinductive properties required to support bone healing in large defects. In this article, we study the osteoinductive potential of calcium phosphate ceramic particles implanted for 6 months into the dorsal muscles of eight adult female sheep. Microporous biphasic calcium phosphate (MBCP) granules of 1-2 mm composed of hydroxyapatite and beta-tricalcium phosphate (60/40) had macropores of 450 microm, micropores of 0.43 microm, and a specific surface area of 1.8 m(2)/g. After 6 months in the back muscles of sheep, the explants composed of MBCP granules were hard and encapsulated by normal muscle tissue. Ectopic bone formation with Haversian structures was observed in close contact with the MBCP granules in histological sections. Back-scattered electron microscopy and micro-computed tomography indicated that approximately 10% of well-mineralized bone with mature osteocytes had formed between or upon the granules. The ectopic bone showed trabeculae bridging the MBCP granules. Both the number and thickness of the trabeculae formed between the MBCP particles were comparable to those measured in spongious bone. The overall results therefore confirmed the presence of mature bone after intramuscular implantation of MBCP granules. The different hypotheses explaining ectopic bone formation induced by MBCP granules are discussed. Synthetic bone substitutes with osteoinductive properties could be used in bone reconstructive surgery. PMID:15869915

Le Nihouannen, Damien; Daculsi, Guy; Saffarzadeh, Afchine; Gauthier, Olivier; Delplace, Séverine; Pilet, Paul; Layrolle, Pierre

2005-06-01

138

Circulating leptin is negatively associated with the isotopically-measured bone formation rate in pubertal adolescents  

Technology Transfer Automated Retrieval System (TEKTRAN)

BACKGROUND: Animal studies show that serum leptin (SL) is associated with decreased bone formation (BF) and increased bone resorption (BR) rates via its effects on the sympathetic nervous system. Pediatric data on these relationships are limited due to lack of accurate methodology for in vivo assess...

139

Regulation of bone resorption and formation by purines and pyrimidines  

E-print Network

an organic collagen matrix, and three major cell types: osteoclasts, osteoblasts and osteocytes (Table 1; Fig. Some osteoblasts become incorporated in the bone matrix they secrete, differentiating into osteocytes Differentiate into osteocytes (network of strain- detecting cells) when engulfed by bone matrix; p

Burnstock, Geoffrey

140

The circadian modulation of leptin-controlled bone formation  

Technology Transfer Automated Retrieval System (TEKTRAN)

Mice with circadian gene Period and Cryptochrome mutations develop high bone mass early in life. Such a phenotype is accompanied by an increase in osteoblast numbers in mutant bone and cannot be corrected by leptin intracerebroventricular infusion. Thus, the molecular clock plays a key role in lepti...

141

Normal Tempo of Bone Formation in Turner Syndrome despite Signs of Accelerated Bone Resorption  

Microsoft Academic Search

Aims: To evaluate area bone mineral density (aBMD) and volumetric BMD (vBMD) by dual-energy X-ray absorptiometry, and relations to bone markers and hormones in adolescent women with Turner syndrome (TS). Methods: Cross-sectional study in TS patients (n = 37, 16.7 ± 3.4 years) and control group (n = 49), assessed by dual-energy X-ray absorptiometry, bone markers and hormones. TS patients

Line Cleemann; Kirsten Holm; Hanne Kobbernagel; Sven O. Skouby; Bent Kristensen; Heidi Smedegaard; Anna-Maria Andersson; Arieh Cohen; Claus H. Gravholt

2011-01-01

142

Skeletal Repair by in Situ Formation of the Mineral Phase of Bone  

Microsoft Academic Search

A process has been developed for the in situ formation of the mineral phase of bone. Inorganic calcium and phosphate sources are combined to form a paste that is surgically implanted by injection. Under physiological conditions, the material hardens in minutes concurrent with the formation of dahllite. After 12 hours, dahllite formation was nearly complete, and an ultimate compressive strength

Brent R. Constantz; Ira C. Ison; Mark T. Fulmer; Robert D. Poser; Susanne T. Smith; Michelle Vanwagoner; John Ross; Steven A. Goldstein; Jesse B. Jupiter; Daniel I. Rosenthal

1995-01-01

143

Porous ceramic titanium dioxide scaffolds promote bone formation in rabbit peri-implant cortical defect model.  

PubMed

Titanium oxide (TiO?) scaffolds have previously been reported to exhibit very low mechanical strength. However, we have been able to produce a scaffold that features a high interconnectivity, a porosity of 91% and a compressive strength above 1.2 MPa. This study analyzed the in vivo performance of the porous TiO? scaffolds in a peri-implant cortical defect model in the rabbit. After 8 weeks of healing, morphological microcomputed tomography analyses of the defects treated with the TiO? scaffolds had significantly higher bone volume, bone surface and bone surface-to-volume ratio when compared to sham, both in the cortical and bone marrow compartment. No adverse effects, i.e. tissue necrosis or inflammation as measured by lactate dehydrogenase activity and real-time reverse transcription polymerase chain reaction analysis, were observed. Moreover, the scaffold did not hinder bone growth onto the adjacent cortical titanium implant. Histology clearly demonstrated new bone formation in the cortical sections of the defects and the presence of newly formed bone in close proximity to the scaffold surface and the surface of the adjacent Ti implant. Bone-to-material contact between the newly formed bone and the scaffold was observed in the histological sections. Islets of new bone were also present in the marrow compartment albeit in small amounts. In conclusion, the present investigation demonstrates that TiO? scaffolds osseointegrate well and are a suitable scaffold for peri-implant bone healing and growth. PMID:22985740

Haugen, Håvard Jostein; Monjo, Marta; Rubert, Marina; Verket, Anders; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik; Rønold, Hans Jacob; Wohlfahrt, Johan Caspar

2013-02-01

144

Up-regulation of glycolytic metabolism is required for HIF1?-driven bone formation  

PubMed Central

The bone marrow environment is among the most hypoxic in the body, but how hypoxia affects bone formation is not known. Because low oxygen tension stabilizes hypoxia-inducible factor alpha (HIF?) proteins, we have investigated the effect of expressing a stabilized form of HIF1? in osteoblast precursors. Brief stabilization of HIF1? in SP7-positive cells in postnatal mice dramatically stimulated cancellous bone formation via marked expansion of the osteoblast population. Remarkably, concomitant deletion of vascular endothelial growth factor A (VEGFA) in the mouse did not diminish bone accrual caused by HIF1? stabilization. Thus, HIF1?-driven bone formation is independent of VEGFA up-regulation and increased angiogenesis. On the other hand, HIF1? stabilization stimulated glycolysis in bone through up-regulation of key glycolytic enzymes including pyruvate dehydrogenase kinase 1 (PDK1). Pharmacological inhibition of PDK1 completely reversed HIF1?-driven bone formation in vivo. Thus, HIF1? stimulates osteoblast formation through direct activation of glycolysis, and alterations in cellular metabolism may be a broadly applicable mechanism for regulating cell differentiation. PMID:24912186

Regan, Jenna N.; Lim, Joohyun; Shi, Yu; Joeng, Kyu Sang; Arbeit, Jeffrey M.; Shohet, Ralph V.; Long, Fanxin

2014-01-01

145

Lamellar Keratoplasty: A Literature Review  

PubMed Central

The concept of lamellar keratoplasty (LK) is not new. However, newer forms of lamellar keratoplasty techniques have emerged in the last decade or so revolving around the concept of targeted replacement of diseased corneal layers. These include anterior lamellar keratoplasty (ALK) techniques that aim to selectively replace diseased corneal stroma and endothelial keratoplasty techniques aiming to replaced damaged endothelium in endothelial disorders. Recent improvements in surgical instruments and introduction of new techniques as well as inherent advantages such as preservation of globe integrity and decreased graft rejection have resulted in the reintroduction of LK as an acceptable alternative to conventional PK. In this review, indications, benefits, limitations, and outcomes of various anterior and posterior lamellar keratoplasty techniques are discussed. PMID:24223301

Espandar, Ladan; Carlson, Alan N.

2013-01-01

146

Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats.  

PubMed

A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro-computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, ?-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities, and imply that PEMF might become a potential biophysical treatment modality for disuse osteoporosis. PMID:24753111

Jing, Da; Cai, Jing; Wu, Yan; Shen, Guanghao; Li, Feijiang; Xu, Qiaoling; Xie, Kangning; Tang, Chi; Liu, Juan; Guo, Wei; Wu, Xiaoming; Jiang, Maogang; Luo, Erping

2014-10-01

147

The Clock Genes Period 2 and Cryptochrome 2 Differentially Balance Bone Formation  

PubMed Central

Background Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings We found that Per2Brdm1 mutant mice as well as mice lacking Cry2?/? displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2?/? displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2?/? mutants despite the simultaneous inactivation of Per2. Conclusions/Significance This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters. PMID:20634945

Seitz, Sebastian; Schinke, Thorsten; Schmutz, Isabelle; van der Horst, Gijsbertus; Amling, Michael; Albrecht, Urs

2010-01-01

148

Effect of low gravity on calcium metabolism and bone formation (L-7)  

NASA Technical Reports Server (NTRS)

Recently, attention has been focused on the disorders of bone and calcium metabolism during space flight. The skeletal system has evolved on the Earth under 1-g. Space flights under low gravity appear to cause substantial changes in bone and calcium homeostasis of the animals adapted to 1-g. A space experiment for the First Materials Processing Test (FMPT) was proposed to examine the effects of low gravity on calcium metabolism and bone formation using chick embryos loaded in a space shuttle. This space experiment was proposed based on the following two experimental findings. First, it has been reported that bone density decreases significantly during prolonged space flight. The data obtained from the US Skylab and the U.S.S.R. Salyut-6 cosmonauts have also documented that the degree of bone loss is related to the duration of space flight. Second, the US-Soviet joints space experiment demonstrated that the decrease in bone density under low gravity appears to be due to the decrease in bone formation rather than the increase in bone resorption. The purpose of our space experiment is, therefore, to investigate further the mechanisms of bone growth under low gravity using fertilized chick embryos.

Suda, Tatsuo

1993-01-01

149

Osthole Stimulates Osteoblast Differentiation and Bone Formation by Activation of ?-Catenin–BMP Signaling  

PubMed Central

Osteoporosis is defined as reduced bone mineral density with a high risk of fragile fracture. Current available treatment regimens include antiresorptive drugs such as estrogen receptor analogues and bisphosphates and anabolic agents such as parathyroid hormone (PTH). However, neither option is completely satisfactory because of adverse effects. It is thus highly desirable to identify novel anabolic agents to improve future osteoporosis treatment. Osthole, a coumarin-like derivative extracted from Chinese herbs, has been shown to stimulate osteoblast proliferation and differentiation, but its effect on bone formation in vivo and underlying mechanism remain unknown. In this study, we found that local injection of Osthole significantly increased new bone formation on the surface of mouse calvaria. Ovariectomy caused evident bone loss in rats, whereas Osthole largely prevented such loss, as shown by improved bone microarchitecture, histomorphometric parameters, and biomechanical properties. In vitro studies demonstrated that Osthole activated Wnt/?-catenin signaling, increased Bmp2 expression, and stimulated osteoblast differentiation. Targeted deletion of the ?-catenin and Bmp2 genes abolished the stimulatory effect of Osthole on osteoblast differentiation. Since deletion of the Bmp2 gene did not affect Osthole-induced ?-catenin expression and the deletion of the ?-catenin gene inhibited Osthole-regulated Bmp2 expression in osteoblasts, we propose that Osthole acts through ?-catenin–BMP signaling to promote osteoblast differentiation. Our findings demonstrate that Osthole could be a potential anabolic agent to stimulate bone formation and prevent estrogen deficiency–induced bone loss. © 2010 American Society for Bone and Mineral Research. PMID:20200936

Tang, De-Zhi; Hou, Wei; Zhou, Quan; Zhang, Minjie; Holz, Jonathan; Sheu, Tzong-Jen; Li, Tian-Fang; Cheng, Shao-Dan; Shi, Qi; Harris, Stephen E; Chen, Di; Wang, Yong-Jun

2010-01-01

150

Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats  

SciTech Connect

Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/?CT imaging. GSK-3 inhibitors caused ?-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/?CT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis and mineralisation produced by GSK-3 inhibition. • In rats, 3 GSK-3 inhibitors produced a unique serum bone turnover biomarker profile. • Enhanced bone formation was seen within 7 to 14 days of compound treatment in rats.

Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); O'Shea, Patrick J.; Fagura, Malbinder [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Pilling, James E. [Discovery Sciences, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Sanganee, Hitesh [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Wada, Hiroki [R and I IMed, AstraZeneca R and D, Molndal (Sweden); Courtney, Paul F. [DMPK, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Kavanagh, Stefan; Hall, Peter A. [Safety Assessment, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Escott, K. Jane [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom)

2013-10-15

151

Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations.  

PubMed

Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. PMID:24975579

Esteve-Altava, Borja; Rasskin-Gutman, Diego

2014-09-01

152

Bone formation in rabbit's leg muscle after autologous transplantation of bone marrow-derived mesenchymal stem cells expressing human bone morphogenic protein-2  

PubMed Central

Background: To test whether autologous transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) expressing human bone morphogenic protein-2 (hBMP-2) can produce bone in rabbit leg muscles. Materials and Methods: MSCs were isolated from BM of the iliac crest of rabbits and then infected with lentiviral vectors (LVs) bearing hBMP-2 and green fluorescent protein under the control of the cytomegalovirus (immediate early promoter). Differentiation of transduced MSCs to osteoblasts in vitro was evaluated with an alkaline phosphatase activity assay and immuohistochemistry against osteoblast specific markers. MSCs expressing hBMP-2 were placed in an absorbable gelatin sponge, which was then transplanted into the gastrocnemius of rabbits from which MSCs were isolated. Bone formation was examined by X-ray and histological analysis. Results: LVs efficiently mediated hBMP-2 gene expression in rabbit BM-MSCs. Ectopic expression of hBMP in these MSCs induced osteoblastic differentiation in vitro. Bone was formed after the MSCs expressing hBMP-2 were transplanted into rabbit muscles. Conclusion: Ectopic expression of hBMP-2 in rabbit MSCs induces them to differentiate into osteoblasts in vitro and to form a bone in vivo. PMID:25143636

Wei, Licheng; Lei, Guang-Hua; Yi, Han-Wen; Sheng, Pu-yi

2014-01-01

153

Effect of coating Straumann Bone Ceramic with Emdogain on mesenchymal stromal cell hard tissue formation.  

PubMed

Periodontal tissue engineering requires a suitable biocompatible scaffold, cells with regenerative capacity, and instructional molecules. In this study, we investigated the capacity of Straumann Bone Ceramic coated with Straumann Emdogain, a clinical preparation of enamel matrix protein (EMP), to aid in hard tissue formation by post-natal mesenchymal stromal cells (MSCs) including bone marrow stromal cells (BMSCs) and periodontal ligament fibroblasts (PDLFs). MSCs were isolated and ex vivo-expanded from human bone marrow and periodontal ligament and, in culture, allowed to attach to Bone Ceramic in the presence or absence of Emdogain. Gene expression of bone-related proteins was investigated by real time RT-PCR for 72 h, and ectopic bone formation was assessed histologically in subcutaneous implants of Bone Ceramic containing MSCs with or without Emdogain in NOD/SCID mice. Alkaline phosphatase activity was also assessed in vitro, in the presence or absence of Emdogain. Collagen-I mRNA was up-regulated in both MSC populations over the 72-h time course with Emdogain. Expression of BMP-2 and the osteogenic transcription factor Cbfa-1 showed early stimulation in both MSC types after 24 h. In contrast, expression of BMP-4 was consistently down-regulated in both MSC types with Emdogain. Up-regulation of osteopontin and periostin mRNA was restricted to BMSCs, while higher levels of bone sialoprotein-II were observed in PDLFs with Emdogain. Furthermore, alkaline phosphatase activity levels were reduced in both BMSCs and PDLFs in the presence of Emdogain. Very little evidence was found for ectopic bone formation following subcutaneous implantation of MSCs with Emdogain-coated or -uncoated Bone Ceramic in NOD/SCID mice. The early up-regulation of several important bone-related genes suggests that Emdogain may have a significant stimulatory effect in the commitment of mesenchymal cells to osteogenic differentiation in vitro. While Emdogain inhibited AP activity and appeared not to induce ectopic bone formation, longer-term studies are required to determine whether it promotes the final stages of osteoblast formation and mineralization at gene and protein levels. While used in clinical applications, whether Emdogain and other commercial preparations of EMPs truly possess the capacity to induce the regeneration of bone or other components of the periodontium remains to be established. PMID:21584694

Mrozik, Krzysztof Marek; Gronthos, Stan; Menicanin, Danijela; Marino, Victor; Bartold, P Mark

2012-06-01

154

Analysis of bone formation after sinus augmentation using ?-tricalcium phosphate.  

PubMed

Implant placement in the edentulous maxilla often represents a clinical challenge due to insufficient bone height after crestal bone resorption and maxillary sinus pneumatization. Several graft materials have been evaluated for augmenting the maxillary sinus to compensate for the lost vertical dimension. Allografts are readily available without the risk of disease transmission and the need for a second site surgery. The aim of this case series was to systematically evaluate the development and maturation of augmented bone in the maxillary sinus using beta-tricalcium phosphate. In 21 to 40 weeks post-sinus elevation, bone biopsies were taken and implants placed simultaneously. All specimens were demineralized and subjected to staining procedures (ie, Hematoxylin and Eosin [H&E], Goldner's staining, and tartrate-resistant acid phosphatase [TRAP]). Total bone increased over time, whereas the amount of graft material diminished. A lack of inflammatory reaction was noticed with the use of this graft material. In addition, TRAP staining revealed the presence of osteoclasts surrounding the remaining particles. During a 12-month follow-up, no implant failure or complications were observed. PMID:22616219

Schulze-Späte, Ulrike; Dietrich, Thomas; Kayal, Rayyan A; Hasturk, Hatice; Dobeck, Justine; Skobe, Ziedonis; Dibart, Serge

2012-05-01

155

Prednisone-induced osteopenia in beagles: variable effects mediated by differential suppression of bone formation.  

PubMed

To examine the mechanism of glucocorticoid-induced osteopenia and the basis for variable bone loss after glucocorticoid administration, we gave prednisone (1.3 mg.kg-1.day-1) to normal male dogs (n = 15) for 29 wk to attempt induction of osteopenia. Compared with age-matched control dogs (n = 14), prednisone treatment rapidly decreased spinal bone density by 4.3%, as assessed by quantitative digital radiography, and reduced trabecular bone volume by 14.6%, as measured by quantitative histomorphology of iliac crest bone specimens. Bone loss was attenuated in prednisone-treated dogs after prolonged treatment (greater than 12 wk). Prednisone treatment resulted in diminished bone formation rates (15 +/- 3.4 vs. 47 +/- 4.5 microns/yr) and activation frequency (0.4 +/- 0.1 vs. 1.3 +/- 0.2/day). These findings indicate that suppression of osteoblastic function and recruitment is the primary histological abnormality mediating glucocorticoid-induced osteopenia in beagles. In contrast, prednisone administration had no effect on bone resorption or serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D, which suggests that these factors are not essential for prednisone-induced bone loss. Moreover, 33% of beagles were totally resistant to glucocorticoid-induced osteopenia. Such heterogeneity of bone loss was associated with variable suppressive effects of prednisone on osteoblastic function, as evidenced by greater bone formation rates and activation frequency in prednisone-resistant animals. Collectively, these observations suggest that glucocorticoid-induced bone loss results from a dynamic interplay between steroid-mediated suppression of osteoblastic function and recruitment and undefined compensatory factors that ameliorate the effects of glucocorticoids on osteoblastic precursors. PMID:1636691

Quarles, L D

1992-07-01

156

Ectopic osteoid and bone formation by three calcium-phosphate ceramics in rats, rabbits and dogs.  

PubMed

Calcium phosphate ceramics with specific physicochemical properties have been shown to induce de novo bone formation upon ectopic implantation in a number of animal models. In this study we explored the influence of physicochemical properties as well as the animal species on material-induced ectopic bone formation. Three bioceramics were used for the study: phase-pure hydroxyapatite (HA) sintered at 1200°C and two biphasic calcium phosphate (BCP) ceramics, consisting of 60 wt.% HA and 40 wt.% TCP (?-Tricalcium phosphate), sintered at either 1100°C or 1200°C. 108 samples of each ceramic were intramuscularly implanted in dogs, rabbits, and rats for 6, 12, and 24 weeks respectively. Histological and histomorphometrical analyses illustrated that ectopic bone and/or osteoid tissue formation was most pronounced in BCP sintered at 1100°C and most limited in HA, independent of the animal model. Concerning the effect of animal species, ectopic bone formation reproducibly occurred in dogs, while in rabbits and rats, new tissue formation was mainly limited to osteoid. The results of this study confirmed that the incidence and the extent of material-induced bone formation are related to both the physicochemical properties of calcium phosphate ceramics and the animal model. PMID:25229501

Wang, Liao; Zhang, Bi; Bao, Chongyun; Habibovic, Pamela; Hu, Jing; Zhang, Xingdong

2014-01-01

157

Formation of hollow bone-like morphology of calcium carbonate on surfactant/polymer templates  

NASA Astrophysics Data System (ADS)

Novel hollow, bone-like structures of Precipitated Calcium Carbonate (PCC) are fabricated, for the first time, starting from naturally occurring dolomite. The hollow, bone-like structures are prepared by precipitating calcium carbonate on self-assembled poly(acrylic acid)/cetyltrimethylammonium chloride (PAA/CTAC) template. Fourier Transform Infrared Spectroscopy (FT-IR), X-ray diffraction (XRD), Transmission Electron Microscopy (TEM) and Field Emission Scanning Electron Microscopic (FE-SEM) studies reveal that the bone-like structure is composed of Amorphous Calcium Carbonate (ACC) nanoparticles in the center and calcite nanoparticles at the edges. Bone-like PCC particles are in particle length of 2-3 ?m and particle width of 1 ?m. The internal hollow structures of bone-like particles are observed from TEM images. As identified by FE-SEM images, the bone-like structure has been formed through the crystal growth of initially formed ACC nanoparticles. The ACC particles are stabilized in the center while the calcite crystals have been grown from the ACC toward the edges of the structure to form a bone-like morphology. We also propose a possible mechanism for the formation of hollow bone-like PCC in this study. The fabricated hollow, bone-like PCC has potential applications in the preparation of release systems such as drugs, cosmetics and pigments.

Mantilaka, M. M. M. G. P. G.; Pitawala, H. M. T. G. A.; Rajapakse, R. M. G.; Karunaratne, D. G. G. P.; Upul Wijayantha, K. G.

2014-04-01

158

Microencapsulated rBMMSCs/calcium phosphate cement for bone formation in vivo.  

PubMed

As an injectable scaffold material for bone tissue engineering, calcium phosphate cement (CPC) has good biocompatibility, self-setting, and osteoconduction properties. Alginate-microencapsulated seed cells can pick up the degradation speed and bioactivity of CPC. The aim of this study was to explore the osteogenic ability of a composite of microencapsulated rabbit bone marrow mesenchymal stem cells (rBMMSCs) with ?-tricalcium phosphate/calcium phosphate cement (?-TCP/CPC) in vivo. Cavity defects were created in both femoral condylar regions of New Zealand White rabbits. ?-TCP/CPC (control group) and alginate microencapsulated rBMMSCs/?-TCP/CPC composite (composite group) were implanted separately into the bone defects of both femurs. Bone substitute degradation and new bone formation were evaluated by CBCT, and the defects were examined histologically 8, 16, and 24 weeks after implantation. In addition, fluorescent carbocyanine CM-Dil was used to track the rBMMSCs in vivo after implantation. The results showed that far more new bone and bone marrow grew into the bone defects in the composite group. Few CM-Dil labeled positive cells were observed postoperatively. However more native cells were detected in the graft areas of the composite group than those of the control group. The study indicates that a composite of microencapsulated seed cells/?-TCP/CPC might be considered as a promising injectable material for the generation of new bone tissue. PMID:24211970

Wang, Juan; Qiao, Pengyan; Dong, Limin; Li, Fangfang; Xu, Tao; Xie, Qiufei

2014-01-01

159

Enhanced control of in vivo bone formation with surface functionalized alginate microbeads incorporating heparin and human bone morphogenetic protein-2.  

PubMed

In this study, we tested the hypothesis that a surface functionalization delivery platform incorporating heparin onto strontium alginate microbeads surfaces would convert this "naive carriers" into "mini-reservoirs" for localized in vivo delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) that will induce functional bone regeneration. In vitro evaluation confirmed that (1) heparin incorporation could immobilize and prolong rhBMP-2 release for approximately 3 weeks; (2) a significant decrease (p<0.01) in rhBMP-2 burst release is attainable depending on initial protein load; and (3) rhBMP-2 released from surface functionalized microbeads retained bioactivity and stimulated higher alkaline phosphatase activity in cultured C(2)C(12) cells when compared with daily administration of fresh bolus rhBMP-2. Subsequently, surface functionalized microbeads were used for in vivo delivery of rhBMP-2 at local sites of posterolateral spinal fusion surgery in rats. The microbeads were loaded into the pores of medical-grade polyepsilone caprolactone-tricalcium phosphate scaffolds before implantation. Results revealed robust bone formation and a biomechanically solid fusion after 6 weeks. When compared with a control group consisting of an equivalent amount of rhBMP-2 that was directly adsorbed onto bare-surfaced microbeads with no heparin, a 5.3-fold increase in bone volume fraction and a 2.6-fold increase in bending stiffness (flexion/extension) were observed. When compared with collagen sponge carriers of rhBMP-2, a 1.5-fold and a 1.3-fold increase in bone volume fraction and bending stiffness were observed, respectively. More importantly, 3D micro-computed tomography images enabled the visualization of a well-contained newly formed bone at ipsilateral implant sites with surface functionalized rhBMP-2 delivery. This was absent with collagen sponge carriers where newly formed bone tissue was poorly contained and crossed over the posterior midline to contralateral implants. These findings are important because of complications with current rhBMP-2 delivery method, including excessive, uncontrolled bone formation. PMID:22894570

Abbah, Sunny Akogwu; Liu, Jing; Goh, James Cho Hong; Wong, Hee-Kit

2013-02-01

160

Hydroxyapatite grafting promotes new bone formation and osseointegration of smooth titanium implants.  

PubMed

Titanium is the ideal metal for intra-osseous dental implants. It permits the natural formation of an oxide layer on its surface and thereby it prevents the release of potentially toxic molecules. New formation of bone around implants, partially placed into the bone marrow cavity, is a gradual process that runs from the endosteum to the surface of the implant. Deposition of hydroxyapatite crystals on collagen type I fibrils is initiated by acidic proteins and leads to bone mineralization. This study analyzed the effects of hydroxyapatite upon peri-implant bone formation after insertion of smooth titanium implants. Screw-shaped smooth titanium implants of 3.75 mm thickness and 8.5 mm length were inserted into the metaphysis of rabbit tibia, either together with bovine hydroxyapatite into the right tibia or in controls without hydroxyapatite into the left tibia. Polyfluorochrome tracers (alizarin complex, calcein, tetracycline) were injected subcutaneously at different time intervals after implantation to evaluate the time frame of bone new formation over a period of 8 weeks. All samples were processed for histology and analyzed by fluorescence and polarizing microscopy. Our results showed a higher quantity of mature type I collagen fibers around implants and an acceleration of bone formation in the presence of hydroxyapatite. Mainly immature organic matrix was formed at the surface of implants in controls. The presence of hydroxyapatite seems to promote the maturation of collagen fibers surrounding the titanium implants and to support osteoconduction. Moreover, new formation of bone was faster in all samples where implants were inserted together with hydroxyapatite. PMID:16551011

Allegrini, Sergio; Rumpel, Elisabeth; Kauschke, Ellen; Fanghänel, Jochen; König, Bruno

2006-03-01

161

Permian Bone Spring formation: Sandstone play in the Delaware basin. Part I - slope  

SciTech Connect

New exploration in the Permian (Leonardian) Bone Spring formation has indicated regional potential in several sandstone sections across portions of the northern Delaware basin. Significant production has been established in the first, second, and third Bone Spring sandstones, as well as in a new reservoir interval, the Avalon sandstone, above the first Bone Spring sandstone. These sandstones were deposited as submarine-fan systems within the northern Delaware basin during periods of lowered sea level. The Bone Spring as a whole consists of alternating carbonate and siliciclastic intervals representing the downdip equivalents to thick Abo-Yeso/Wichita-Clear Fork carbonate buildups along the Leonardian shelf margin. Hydrocarbon exploration in the Bone Spring has traditionally focused on debris-flow carbonate deposits restricted to the paleoslope. Submarine-fan systems, in contrast, extend a considerable distance basinward of these deposits and have been recently proven productive as much as 40-48 km south of the carbonate trend.

Montgomery, S.L. [Petroleum Consultant, Seattle, WA (United States)

1997-08-01

162

Extrinsic Curvature, Geometric Optics, and Lamellar Order on Curved Substrates  

E-print Network

When thermal energies are weak, two dimensional lamellar structures confined on a curved substrate display complex patterns arising from the competition between layer bending and compression in the presence of geometric constraints. We present broad design principles to engineer the geometry of the underlying substrate so that a desired lamellar pattern can be obtained by self-assembly. Two distinct physical effects are identified as key factors that contribute to the interaction between the shape of the underlying surface and the resulting lamellar morphology. The first is a local ordering field for the direction of each individual layer which tends to minimize its curvature with respect to the three-dimensional embedding. The second is a non-local effect controlled by the intrinsic geometry of the surface that forces the normals to the (nearly incompressible) layers to lie on geodesics, leading to caustic formation as in optics. As a result, different surface morphologies with predominantly positive or negative Gaussian curvature can act as converging or diverging lenses respectively. By combining these ingredients, as one would with different optical elements, complex lamellar morphologies can be obtained. This smectic optometry enables the manipulation of lamellar configurations for the design of novel materials.

R. D. Kamien; D. R. Nelson; C. D. Santangelo; V. Vitelli

2009-08-29

163

Formation of engineered bone with adipose stromal cells from buccal fat pad.  

PubMed

A robust method for inducing bone formation from adipose-derived stromal cells (ADSCs) has not been established. Moreover, the efficacy of strong osteogenic inducers including BMP-2 for ADSC-mediated bone engineering remains controversial. Meanwhile, the buccal fat pad (BFP), which is found in the oral cavity as an adipose-encapsulated mass, has been shown to have potential as a new accessible source of ADSCs for oral surgeons. However, to date, there have been no reports that define the practical usefulness of ADSCs from BFP (B-ADSCs) for bone engineering. Here, we report an efficient method of generating bone from B-ADSCs using rhBMP-2. The analyses show that B-ADSCs can differentiate in vitro toward the osteoblastic lineage by the addition of rhBMP-2 to culture medium, regardless of the presence of osteoinductive reagents (OSR), as demonstrated by measurements of ALP activity, in vitro calcification, and osteogenic gene expression. Interestingly, adipogenic genes were clearly detectable only in cultures with rhBMP-2 and OSR. However, in vivo bone formation was most substantial when B-ADSCs cultured in this condition were transplanted. Thus, B-ADSCs reliably formed engineered bone when pre-treated with rhBMP-2 for inducing mature osteoblastic differentiation. This study supports the potential translation for B-ADSC use in the clinical treatment of bone defects. PMID:22538411

Shiraishi, T; Sumita, Y; Wakamastu, Y; Nagai, K; Asahina, I

2012-06-01

164

Exercise-Induced Bone Formation Is Poorly Linked to Local Strain Magnitude in the Sheep Tibia  

PubMed Central

Functional interpretations of limb bone structure frequently assume that diaphyses adjust their shape by adding bone primarily across the plane in which they are habitually loaded in order to minimize loading-induced strains. Here, to test this hypothesis, we characterize the in vivo strain environment of the sheep tibial midshaft during treadmill exercise and examine whether this activity promotes bone formation disproportionately in the direction of loading in diaphyseal regions that experience the highest strains. It is shown that during treadmill exercise, sheep tibiae were bent in an anteroposterior direction, generating maximal tensile and compressive strains on the anterior and posterior shaft surfaces, respectively. Exercise led to significantly increased periosteal bone formation; however, rather than being biased toward areas of maximal strains across the anteroposterior axis, exercise-related osteogenesis occurred primarily around the medial half of the shaft circumference, in both high and low strain regions. Overall, the results of this study demonstrate that loading-induced bone growth is not closely linked to local strain magnitude in every instance. Therefore, caution is necessary when bone shaft shape is used to infer functional loading history in the absence of in vivo data on how bones are loaded and how they actually respond to loading. PMID:24897411

Wallace, Ian J.; Demes, Brigitte; Mongle, Carrie; Pearson, Osbjorn M.; Polk, John D.; Lieberman, Daniel E.

2014-01-01

165

Vascularized Bone Tissue Formation Induced by Fiber-Reinforced Scaffolds Cultured with Osteoblasts and Endothelial Cells  

PubMed Central

The repair of the damaged bone tissue caused by damage or bone disease was still a problem. Current strategies including the use of autografts and allografts have the disadvantages, namely, diseases transmission, tissue availability and donor morbidity. Bone tissue engineering has been developed and regarded as a new way of regenerating bone tissues to repair or substitute damaged or diseased ones. The main limitation in engineering in vitro tissues is the lack of a sufficient blood vessel system, the vascularization. In this paper, a new-typed hydroxyapatite/collagen composite scaffold which was reinforced by chitosan fibers and cultured with osteoblasts and endothelial cells was fabricated. General observation, histological observation, detection of the degree of vascularization, and X-ray examination had been done to learn the effect of vascularized bone repair materials on the regeneration of bone. The results show that new vessel and bone formed using implant cultured with osteoblasts and endothelial cells. Nanofiber-reinforced scaffold cultured with osteoblasts and endothelial cells can induce vascularized bone tissue formation. PMID:24369019

Liu, Xinhui; Zhang, Guoping; Hou, Chuanyong; Wang, Hua; Yang, Yelin; Guan, Guoping; Dong, Wei; Gao, Hongyang

2013-01-01

166

Dysapoptosis of osteoblasts and osteocytes increases cancellous bone formation but exaggerates cortical porosity with age.  

PubMed

Skeletal aging is accompanied by decreased cancellous bone mass and increased formation of pores within cortical bone. The latter accounts for a large portion of the increase in nonvertebral fractures after age 65 years in humans. We selectively deleted Bak and Bax, two genes essential for apoptosis, in two types of terminally differentiated bone cells: the short-lived osteoblasts that elaborate the bone matrix, and the long-lived osteocytes that are immured within the mineralized matrix and choreograph the regeneration of bone. Attenuation of apoptosis in osteoblasts increased their working lifespan and thereby cancellous bone mass in the femur. In long-lived osteocytes, however, it caused dysfunction with advancing age and greatly magnified intracortical femoral porosity associated with increased production of receptor activator of nuclear factor-?B ligand and vascular endothelial growth factor. Increasing bone mass by artificial prolongation of the inherent lifespan of short-lived osteoblasts, while exaggerating the adverse effects of aging on long-lived osteocytes, highlights the seminal role of cell age in bone homeostasis. In addition, our findings suggest that distress signals produced by old and/or dysfunctional osteocytes are the culprits of the increased intracortical porosity in old age. PMID:23761243

Jilka, Robert L; O'Brien, Charles A; Roberson, Paula K; Bonewald, Lynda F; Weinstein, Robert S; Manolagas, Stavros C

2014-01-01

167

Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption  

E-print Network

fragility in female mice as young as 4 months old. Bone mineral density (BMD) of PXR knockout (PXRKO) mice of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo that these morphological phenotypes actually caused mechanical fragility. Lastly, serum levels of phosphate, calcium

Blumberg, Bruce

168

Is Lipid Profile Associated with Bone Mineral Density and Bone Formation in Subjects with Spinal Cord Injury?  

PubMed Central

Purpose. The association between serum lipids and bone mineral density (BMD) has been investigated previously but, up to now, these relationships have not yet been described in spinal cord injury (SCI). We tried to assess the correlation between serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) and BMD in male subjects with SCI. Methods. Dual-energy X-ray absorptiometry (DXA) was used to assess BMD in femoral neck, trochanter, intertrochanteric zone, and lumbar vertebras. Blood samples were taken to measure serums lipids and bone biomarkers including osteocalcin, cross-linked type I collagen (CTX), and bone alkaline phosphatase (BALP). Partial correlation analysis was used to evaluate the relationships between mentioned measurements after adjustment for weight and age. Results. We found a positive correlation between HDL and femoral neck BMD (P: 0.004, r = 0.33). HDL was negatively correlated with osteocalcin (P: 0.017, r = ?0.31) which was not in consistency with its relationship with BMD. TC and LDL were not related to CTX, BALP and BMD. Conclusion. This study does not support a strong association between serum lipids and BMD in subjects with SCI. Moreover it seems that positive association between HDL and BMD is not mediated through increased bone formation. PMID:25215260

Sabour, Hadis; Norouzi Javidan, Abbas; Latifi, Sahar; Hadian, Mohammad Reza; Emami Razavi, Seyed-Hassan; Shidfar, Farzad; Vafa, Mohammad Reza; Aghaei Meybodi, Hamidreza

2014-01-01

169

Bone formation at a rabbit skull defect by autologous bone marrow cells combined with gelatin microspheres containing TGF-beta1.  

PubMed

The objective of the present study is to investigate the addition effect of transforming growth factor (TGF)-beta1 on the bone formation at a rabbit skull defect induced by autologous bone marrow (BM). Following application of gelatin microspheres containing TGF-beta1, with or without BM cells to skull bone defects, bone formation at the defect was assessed by soft X-ray, dual energy X-ray absorptometry (DEXA), and histological examinations. After implantation for 6 weeks, gelatin microspheres containing 0.05 microg of TGF-beta1 plus 10(6) of BM cells induced bone formation at the 6 mm diameter bone defect. The defect was histologically closed by newly formed bone tissue, whilst both gelatin microspheres containing 0.05 microg of TGF-beta1, and 10(6) and 10(7) of BM cells were ineffective. A DEXA experiment revealed that combination of gelatin microspheres containing TGF-beta1 with BM cells enhanced the bone mineral density at the skull defect to a significantly greater extent than other agents. These findings indicate that a combination of gelatin microspheres containing TGF-beta1 enabled BM cells to enhance the osteoinductive ability, resulting in bone formation even at the cell number at which BM cells alone were ineffective. PMID:11211099

Tabata, Y; Hong, L; Miyamoto, S; Miyao, M; Hashimoto, N; Ikada, Y

2000-01-01

170

The mechanism of antibody formation in mouse bone marrow  

Microsoft Academic Search

The bone marrow (BM) is the major production site of B lymphocytes.\\u000aThe newly formed small B lymphocytes migrate, after a maturation period\\u000aof one or more days, to the peripheral lymphoid organs (spleen, lymph\\u000anodes, tonsils, etc.), where they can be activated by antigen (after\\u000awhich they can differentiate into antibody-forming cells) or die.\\u000aAccording to this view, most

G. Koch

1982-01-01

171

Bone formation: The rules for fabricating a composite ceramic  

SciTech Connect

Bone, teeth and shells are complex composite ceramics which are fabricated at low temperature by living organisms. The detailed understanding of this fabrication process is required if we are to attempt to mimic this low temperature assembly process. The guiding principles and major components are outlined with the intent of establishing non-vital fabrication schemes to form a complex composite ceramic consisting of an organix matrix inorganic crystalline phase. 19 refs.

Caplan, A.I. (Case Western Reserve Univ., Cleveland, OH (USA))

1990-01-01

172

The Novel Zinc Finger-Containing Transcription Factor Osterix Is Required for Osteoblast Differentiation and Bone Formation  

Microsoft Academic Search

We have identified a novel zinc finger-containing transcription factor, called Osterix (Osx), that is specifically expressed in all developing bones. In Osx null mice, no bone formation occurs. In endochondral skeletal elements of Osx null mice, mesenchymal cells, together with osteoclasts and blood vessels, invade the mineralized cartilage matrix. However, the mesenchymal cells do not deposit bone matrix. Similarly, cells

Kazuhisa Nakashima; Xin Zhou; Gary Kunkel; Zhaoping Zhang; Jian Min Deng; Richard R. Behringer; Benoit de Crombrugghe

2002-01-01

173

Apoptosis-associated uncoupling of bone formation and resorption in osteomyelitis  

PubMed Central

The mechanisms underlying the destruction of bone tissue in osteomyelitis are only now being elucidated. While some of the tissue damage associated with osteomyelitis likely results from the direct actions of bacteria and infiltrating leukocytes, perhaps exacerbated by bacterial manipulation of leukocyte survival pathways, infection-induced bone loss predominantly results from an uncoupling of the activities of osteoblasts and osteoclasts. Bacteria or their products can directly increase osteoclast formation and activity, and the inflammatory milieu at sites of infection can further promote bone resorption. In addition, osteoclast activity is critically regulated by osteoblasts that can respond to bacterial pathogens and foster both inflammation and osteoclastogenesis. Importantly, bone loss during osteomyelitis is also brought about by a decline in new bone deposition due to decreased bone matrix synthesis and by increased rates of osteoblast apoptosis. Extracellular bacterial components may be sufficient to reduce osteoblast viability, but the causative agents of osteomyelitis are also capable of inducing continuous apoptosis of these cells by activating intrinsic and extrinsic cell death pathways to further uncouple bone formation and resorption. Interestingly, bacterial internalization appears to be required for maximal osteoblast apoptosis, and cytosolic inflammasome activation may act in concert with autocrine/paracrine death receptor-ligand signaling to induce cell death. The manipulation of apoptotic pathways in infected bone cells could be an attractive new means to limit inflammatory damage in osteomyelitis. However, the mechanism that is the most important in bacterium-induced bone loss has not yet been identified. Furthermore, it remains to be determined whether the host would be best served by preventing osteoblast cell death or by promoting apoptosis in infected cells. PMID:24392356

Marriott, Ian

2013-01-01

174

Prednisolone prevents decreases in trabecular bone mass and strength by reducing bone resorption and bone formation defect in adjuvant-induced arthritic rats.  

PubMed

We examined the effects of prednisolone (PSL) administration in normal female Sprague Dawley rats and adjuvant-induced arthritic rats at the age of 6 weeks. Rats were intramuscularly injected with PSL twice a week at doses of 0 (control), 10, 30, 90, or 270 mg/kg body weight (b.w.). In the normal rats, serum osteocalcin level at 14 days and serum carboxyterminal pyridinoline cross-linked telopeptide of type 1 collagen (1CTP) level at 28 days in the 270 mg/kg dose group was lower than the respective value in control animals. The BMC and the trabecular bone formation rate (BFR/BS) of the lumbar body (L-4) in the 270 mg/kg dose group at 14 and 28 days were significantly lower than the values in the control rats. In the arthritic rats, however, serum osteocalcin levels in the PSL-treated groups did not differ compared with arthritic controls. The serum 1CTP levels in all of the PSL-treated groups were significantly reduced at 28 days. The age-dependent increases in the L4 BMC, BMD, and L-3 ultimate compressive load values were maintained. The BFR/BS values in the 90 mg/kg and 270 mg/kg dose groups were significantly higher than those in the arthritic control rats. The trabecular osteoclast number and surface values in all of the PSL-treated groups were significantly lower than the values in arthritic controls. These data demonstrate that PSL administration prevented reduction in bone mass and strength of the lumbar trabecular bone in adjuvant-induced arthritic rats by reducing the increase in bone resorption and the decrease in bone formation at both the local and systemic levels. PMID:9763147

Okazaki, Y; Tsurukami, H; Nishida, S; Okimoto, N; Aota, S; Takeda, S; Nakamura, T

1998-10-01

175

Assessment of bone formation by biochemical markers in metabolic bone disease: Separation between osteoblastic activity at the cell and tissue level  

Microsoft Academic Search

Summary In this study, serum levels of classical serum markers of bone formation [carboxyterminal propeptide of procollagen type I (S-PICP), bone Gla protein (S-BGP)], and total alkaline phosphatase (S-AP)) were related to the calcium kinetic index of whole skeletal mineralization rate (m) by regression analysis in a variety of metabolic bone diseases. For each disease, the regression coefficient (r) as

P. Charles; C. Hasling; L. Risteli; J. Risteli; L. Mosekilde; E. F. Eriksen

1992-01-01

176

An activating Fgfr3 mutation affects trabecular bone formation via a paracrine mechanism during growth.  

PubMed

The fibroblast growth factor receptor 3 (FGFR3) plays a critical role in the regulation of endochondral ossification. Fgfr3 gain-of-function mutations cause achondroplasia, the most common form of dwarfism, and a spectrum of chondrodysplasias. Despite a significant number of studies on the role of FGFR3 in cartilage, to date, none has investigated the influence of Fgfr3-mediated effects of the growth plate on bone formation. We studied three mouse models, each expressing Fgfr3 mutation either ubiquitously (CMV-Fgfr3(Y367C/+)), in chondrocytes (Col II-Fgfr3(Y367C/+)) or in mature osteoblasts (Col I-Fgfr3(Y367C/+)). Interestingly, we demonstrated that dwarfism with a significant defect in bone formation during growth was only observed in mouse models expressing mutant Fgfr3 in the cartilage. We observed a dramatic reduction in cartilage matrix mineralization and a strong defect of primary spongiosa. Anomalies of primary spongiosa were associated with an increase in osteoclast recruitment and a defect of osteoblasts at the mineralization front. A significant decrease in bone volume, trabecular thickness and number was also observed in the trabecular bone. Interestingly, no anomalies in proliferation and differentiation of primary osteoblasts from CMV-Fgfr3(Y367C/+) mice were observed. Based on these data, we excluded a potential function of Fgfr3 directly on osteoblasts at 3 weeks of age and we obtained evidence that the disorganization of the growth plate is responsible for the anomalies of the trabecular bone during bone formation. Herein, we propose that impaired FGFR3 signaling pathways may affect trabecular bone formation via a paracrine mechanism during growth. These results redefine our understanding of endochondral ossification in FGFR3-related chondrodysplasias. PMID:22367969

Mugniery, Emilie; Dacquin, Romain; Marty, Caroline; Benoist-Lasselin, Catherine; de Vernejoul, Marie-Christine; Jurdic, Pierre; Munnich, Arnold; Geoffroy, Valérie; Legeai-Mallet, Laurence

2012-06-01

177

In vivo stimulation of bone formation by aluminum and oxygen plasma surface-modified magnesium implants.  

PubMed

A newly developed magnesium implant is used to stimulate bone formation in vivo. The magnesium implant after undergoing dual aluminum and oxygen plasma implantation is able to suppress rapid corrosion, leaching of magnesium ions, as well as hydrogen gas release from the biodegradable alloy in simulated body fluid (SBF). No released aluminum is detected from the SBF extract and enhanced corrosion resistance properties are confirmed by electrochemical tests. In vitro studies reveal enhanced growth of GFP mouse osteoblasts on the aluminum oxide coated sample, but not on the untreated sample. In addition to that a small amount (50 ppm) of magnesium ions can enhance osteogenic differentiation as reported previously, our present data show a low concentration of hydrogen can give rise to the same effect. To compare the bone volume change between the plasma-treated magnesium implant and untreated control, micro-computed tomography is performed and the plasma-treated implant is found to induce significant new bone formation adjacent to the implant from day 1 until the end of the animal study. On the contrary, bone loss is observed during the first week post-operation from the untreated magnesium sample. Owing to the protection offered by the Al2O3 layer, the plasma-treated implant degrades more slowly and the small amount of released magnesium ions stimulate new bone formation locally as revealed by histological analyses. Scanning electron microscopy discloses that the Al2O3 layer at the bone-implant interface is still present two months after implantation. In addition, no inflammation or tissue necrosis is observed from both treated and untreated implants. These promising results suggest that the plasma-treated magnesium implant can stimulate bone formation in vivo in a minimal invasive way and without causing post-operative complications. PMID:24060425

Wong, Hoi Man; Zhao, Ying; Tam, Vivian; Wu, Shuilin; Chu, Paul K; Zheng, Yufeng; To, Michael Kai Tsun; Leung, Frankie K L; Luk, Keith D K; Cheung, Kenneth M C; Yeung, Kelvin W K

2013-12-01

178

The Importance of the Prenyl Group in the Activities of Osthole in Enhancing Bone Formation and Inhibiting Bone Resorption In Vitro  

PubMed Central

Osteoporosis treatment always aimed at keeping the balance of bone formation and bone resorption. Recently, prenyl group in natural products has been proposed as an active group to enhance the osteogenesis process. Osthole has both the prenyl group and bone-protective activities, but the relationship is still unknown. In this study we found that osthole exerted a potent ability to promote proliferation and osteogenic function of rat bone marrow stromal cells and osteoblasts, including improved cell viability, alkaline phosphatase activity, enhanced secretion of collagen-I, bone morphogenetic protein-2, osteocalcin and osteopontin, stimulated mRNA expression of insulin-like growth factor-1, runt-related transcription factor-2, osterix, OPG (osteoprotegerin), RANKL (receptor activator for nuclear factor-?B ligand), and the ratio of OPG/RANKL, as well as increasing the formation of mineralized nodules. However, 7-methoxycoumarin had no obvious effects. Osthole also inhibited osteoclastic bone resorption to a greater extent than 7-methoxycoumarin, as shown by a lower tartrate-resistant acid phosphatase activity and lower number and smaller area of resorption pits. Our findings demonstrate that osthole could be a potential agent to stimulate bone formation and inhibit bone resorption, and the prenyl group plays an important role in these bone-protective effects. PMID:25147567

Zhai, Yuan-Kun; Pan, Ya-Lei; Niu, Yin-Bo; Li, Chen-Rui; Wu, Xiang-Long; Fan, Wu-Tu; Lu, Ting-Li; Mei, Qi-Bing; Xian, Cory J.

2014-01-01

179

Nanoscale Confinement Controls the Crystallization of Calcium Phosphate: Relevance to Bone Formation  

PubMed Central

A key feature of biomineralization processes is that they take place within confined volumes, in which the local environment can have significant effects on mineral formation. Herein, we investigate the influence of confinement on the formation mechanism and structure of calcium phosphate (CaP). This is of particular relevance to the formation of dentine and bone, structures of which are based on highly mineralized collagen fibrils. CaP was precipitated within 25–300 nm diameter, cylindrical pores of track etched and anodised alumina membranes under physiological conditions, in which this system enables systematic study of the effects of the pore size in the absence of a structural match between the matrix and the growing crystals. Our results show that the main products were polycrystalline hydroxapatite (HAP) rods, together with some single crystal octacalcium phosphate (OCP) rods. Notably, we demonstrate that these were generated though an intermediate amorphous calcium phosphate (ACP) phase, and that ACP is significantly stabilised in confinement. This effect may have significance to the mineralization of bone, which can occur through a transient ACP phase. We also show that orientation of the HAP comparable, or even superior to that seen in bone can be achieved through confinement effects alone. Although this simple experimental system cannot be considered, a direct mimic of the in vivo formation of ultrathin HAP platelets within collagen fibrils, our results show that the effects of physical confinement should not be neglected when considering the mechanisms of formation of structures, such as bones and teeth. PMID:24115275

Cantaert, Bram; Beniash, Elia; Meldrum, Fiona C.

2015-01-01

180

Factors and Mechanisms Involved in the Coupling from Bone Resorption to Formation: How Osteoclasts Talk to Osteoblasts  

PubMed Central

Bone remodeling is the fundamental means by which the quality as well as quantity of the skeleton is maintained throughout adult life. When bone remodeling goes awry, a metabolic bone disease such as osteoporosis ensues. Among multiple phases of the complex remodeling process, we focus in this review on factors and mechanisms that are involved in the coupling of bone formation to preceding resorption. PMID:25247154

Takeshita, Sunao

2014-01-01

181

Titanium nanotubes activate genes related to bone formation in vitro  

PubMed Central

Background: Titanium is used worldwide to make osseointegrable devices, thanks to its favorable characteristics as mechanical proprieties and biocompatibility, demonstrated by in vivo studies with animal models and clinical trials over a forty-year period. However, the exact genetic effect of the titanium layer on cells is still not well characterized. Materials and Methods: To investigate how titanium nanotubes stimulate osteoblasts differentiation and proliferation, some osteoblast genes (SP7, RUNX2, COL3A1, COL1A1, ALPL, SPP1 and FOSL1) were analyzed by quantitative Real Time RT- PCR. Results: After 15 days, osteoblasts cultivated on titanium naotube showed the up-regulation of bone related genes SP7, ENG, FOSL1 and SPP1 and the down-regulation of RUNX2, COL3A1, COL1A1, and ALPL. After 30 days of treatment, the bone related genes SP7, ENG, FOSL1 and RUNX2 were up-regulated while COL3A1, COL1A1, ALPL and SPP1 were down-regulated. Conclusions: Our results, demonstrates that titanium nanotubes can lead to osteoblast differentiation and extracellular matrix deposition and mineralization in dental pulp stem cells by the activation of osteoblast related genes SPP1, FOSL1 and RUNX2. PMID:23814577

Pozio, Alfonso; Palmieri, Annalisa; Girardi, Ambra; Cura, Francesca; Carinci, Francesco

2012-01-01

182

In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes  

PubMed Central

The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co- cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes. PMID:7175438

1982-01-01

183

The effect of fresh bone marrow cells on reconstruction of mouse calvarial defect combined with calvarial osteoprogenitor cells and collagen/apatite scaffold  

PubMed Central

Fresh bone marrow cells have already exhibited its advantages as osteogenic donor cells, but the combination between fresh bone marrow cells and other donor cells utilized for bone healing has not been fully explored. To highlight the impact of fresh bone marrow cells on scaffold-based bone regeneration, single or a combination of calvarial osteoprogenitor cells (OPC) and bone marrow cells (BMC) were used as donor cells combined with collagen/apatite scaffold for calravieal defect healing. The host and donor contributions to bone formation were assessed using histological and GFP imaging analysis. Although the amount of new bone formed by different cell sources did not show significant differences, the origin of the bone formation in the defects mainly depended on the types of donor cells employed: when only calvarial OPC were used as donor cells, a donor-derived bone healing instead of host-derived bone ingrowth was observed; when only fresh BMC were loaded, the host bone could grow into the defect along the lamellar structure of the scaffolds, but the amount of new bone formed was significantly lower than the defect loaded with calvarial OPC only. The combination of calvarial OPC and fresh BMC had similar amount of new bone formation as the group loaded with calvarial osteoprogenitors alone, but did not induce any host-derived bone formation. These results provide compelling evidence of the importance of fresh BMC to induce host-implant integration in bone tissue engineering. PMID:22473786

Yu, Xiaohua; Wang, Liping; Peng, Fei; Jiang, Xi; Xia, Zengmin; Huang, Jianping; Rowe, David; Wei, Mei

2014-01-01

184

A case of refractory perforation at the floor of the mouth with ectopic bone formation.  

PubMed

Although most fistulae are not problematic, surgeons occasionally encounter recurrent and/or refractory fistulae in the field of oral and maxillofacial surgery. In this case report, the authors describe a case in which a patient experienced a recurrent and refractory fistula or perforation at his oral floor through the submandible, with heterotopic bone formation arising on both sides of the mylohyoid line. These heterotopic bones were connected to each other, forming a bone bridge at the center of the oral floor. A fistulectomy and wound closure with a tongue flap was successful. The perforation has not recurred after over four years of follow-up, and the bone bridge is still present. PMID:22586833

Ohba, Seigo; Sekine, Joji; Tobita, Takayoshi; Ikeda, Hideyoshi; Asahina, Izumi

2011-07-01

185

S-nitroso albumin enhances bone formation in a rabbit calvaria model.  

PubMed

Nitric oxide (NO) is a mediator involved in bone regeneration. We therefore examined the effect of the novel NO donor, S-nitroso human serum albumin (S-NO-HSA) on bone formation in a rabbit calvaria augmentation model. Circular grooves (8 mm diameter, two per animal) were created by a trephine drill in the cortical bone of 40 rabbits and titanium caps were placed on the rabbit calvaria bone filled with a collagen sponge soaked with either 100 ?L S-NO-HSA (5%, 20%) or human albumin (5%, 20%). After 4 weeks the titanium hemispheres were subjected to histological and histomorphometric analysis. Bone formation and the volume of the residual collagen sponge were evaluated. S-NO-HSA treatment groups had a significantly higher volume of newly formed bone underneath the titanium hemispheres compared to the albumin control groups (5%: 15.5 ± 4.0% versus 10.6 ± 2.9%; P < 0.05; 20%: 14.0 ± 4.6% versus 6.0 ± 3.8%; P < 0.01). The volume of residual collagen sponge was also significantly lower in the S-NO-HSA groups compared to the control groups (5%: 0.4 ± 0.5% versus 2.6 ± 2.4%; P < 0.05 and 20%: 1.5 ± 2.7% versus 13.0 ± 18.7%; P < 0.01). This study demonstrates for the first time that S-NO-HSA promotes bone formation by slow NO release. Additionally, S-NO-HSA increases collagen sponge degradation. PMID:24113133

Fügl, A; Gasser, H; Watzak, G; Bucher, A; Feierfeil, J; Jürgens, G; Watzek, G; Hallström, S; Gruber, R

2014-03-01

186

3D analysis of bone formation around titanium implants using micro-computed tomography (?CT)  

NASA Astrophysics Data System (ADS)

The quantitative analysis of bone formation around biofunctionalised metallic implants is an important tool for the further development of implants with higher success rates. This is, nowadays, especially important in cases of additional diseases like diabetes or osteoporosis. Micro computed tomography (?CT), as non-destructive technique, offers the possibility for quantitative three-dimensional recording of bone close to the implant's surface with micrometer resolution, which is the range of the relevant bony structures. Within different animal models using cylindrical and screw-shaped Ti6Al4V implants we have compared visualization and quantitative analysis of newly formed bone by the use of synchrotron-radiation-based CT-systems in comparison with histological findings. The SR?CT experiments were performed at the beamline BW 5 (HASYLAB at DESY, Hamburg, Germany; at the BAMline (BESSY, Berlin, Germany). For the experiments, PMMA-embedded samples were prepared with diameters of about 8 mm, which contain in the center the implant surrounded by the bony tissue. To (locally) quantify the bone formation, models were developed and optimized. The comparison of the results obtained by SR?CT and histology demonstrates the advantages and disadvantages of both approaches, although the bone formation values for the different biofunctionalized implants are identical within the error bars. SR?CT allows the clear identification of fully mineralized bone around the different titanium implants. As hundreds of virtual slices were easily generated for the individual samples, the quantification and interactive bone detection led to conclusions of high precision and statistical relevance. In this way, SR?CT in combination with interactive data analysis is proven to be more significant with respect to classical histology.

Bernhardt, Ricardo; Scharnweber, Dieter; Müller, Bert; Beckmann, Felix; Goebbels, Jürgen; Jansen, John; Schliephake, Henning; Worch, Hartmut

2006-08-01

187

Transgenic Overexpression of Ephrin B1 in Bone Cells Promotes Bone Formation and an Anabolic Response to Mechanical Loading in Mice  

PubMed Central

To test if ephrin B1 overexpression enhances bone mass, we generated transgenic mice overexpressing ephrin B1 under the control of a 3.6 kb rat collagen 1A1 promoter (Col3.6-Tgefnb1). Col3.6-Tgefnb1 mice express 6-, 12- and 14-fold greater levels of full-length ephrin B1 protein in bone marrow stromal cells, calvarial osteoblasts, and osteoclasts, respectively. The long bones of both genders of Col3.6-Tgefnb1 mice have increased trabecular bone volume, trabecular number, and trabecular thickness and decreased trabecular separation. Enhanced bone formation and decreased bone resorption contributed to this increase in trabecular bone mass in Col3.6-Tgefnb1 mice. Consistent with these findings, our in vitro studies showed that overexpression of ephrin B1 increased osteoblast differentiation and mineralization, osterix and collagen 1A1 expression in bone marrow stromal cells. Interaction of ephrin B1 with soluble clustered EphB2-Fc decreased osteoclast precursor differentiation into multinucleated cells. Furthermore, we demonstrated that the mechanical loading-induced increase in EphB2 expression and newly formed bone were significantly greater in the Col3.6-Tgefnb1 mice than in WT littermate controls. Our findings that overexpression of ephrin B1 in bone cells enhances bone mass and promotes a skeletal anabolic response to mechanical loading suggest that manipulation of ephrin B1 actions in bone may provide a means to sensitize the skeleton to mechanical strain to stimulate new bone formation. PMID:23874863

Cheng, Shaohong; Kesavan, Chandrasekhar; Mohan, Subburaman; Qin, Xuezhong; Alarcon, Catrina M.; Wergedal, Jon; Xing, Weirong

2013-01-01

188

Chondroid syringoma with extensive bone formation: a case report and review of the literature.  

PubMed

Chondroid syringoma is a rare, skin appendageal tumour, usually reported at the head and neck region. It is a mostly intradermal and rarely subcutaneous small painless nodule. The histopathological examination is characterized by a combination of epithelial and myoepithelial structures within a chondromyxoid and fibrous stroma. Herein, we present a rare case of chondroid syringoma with extensive bone formation. PMID:25478357

Bedir, Recep; Yurdakul, Cuneyt; Sehitoglu, Ibrahim; Gucer, Hasan; Tunc, Suphan

2014-10-01

189

Sequential expression of osteoblast phenotypic genes during medullary bone formation and resorption in estrogen-treated male Japanese quails.  

PubMed

Medullary bone is formed reticularly in the bone marrow cavity of the long bones of female birds. Although this bone matrix contains fewer collagen fibers and more acid mucopolysaccharides than cortical bone, it is not clear that the expression pattern of osteoblast phenotypic genes during bone remodeling. Therefore, 17?-estradiol (E2)-treated male Japanese quails were used to examine the temporal expression patterns of osteoblast phenotypic genes, and to simultaneously confirm the morphological changes occurring in the bone marrow cavity during medullary bone formation and resorption. After E2 treatment, bone lining cells proliferated and developed into mature osteoblasts that had intense alkaline phosphatase (ALP) activity. These cells began to form medullary bone that contained acid mucopolysaccharides and tartrate-resistantacid phosphatase. Runt-related gene 2 (Runx2) mRNA was stably expressed throughout the process. The expression of both ALP and type I collagen mRNAs increased initially, and then rapidly decreased after day 7, while osteoclasts began to resorb medullary bone at day 5. The expression of bone matrix-related genes peaked at day 5, and suddenly decreased at day 7, except for osteopontin. Taken together with these results, the expression patterns of bone matrix-related genes during the later stages might be related to osteoclast activity. Additionally, the constant expression of Runx2 during bone formation and resorption suggested that osteoprogenitor cells always exist in the bone marrow cavity. Therefore, the expression patterns of these genes and the characteristics of bone matrix might extremely be related to the quick remodeling of medullary bone. PMID:22711567

Hiyama, Shinji; Sugiyama, Toshie; Kusuhara, Seiji; Uchida, Takashi

2012-07-01

190

[Influence of high molecular weight polyethylene on viability of osteoblasts and new bone formation].  

PubMed

To investigate the influence of high molecular weight polyethylene (HMWP) on the viability of osteoblasts and new bone formation in the process of fracture healing, the osteoblasts derived from adult human bone marrow were cultured in HMWP maceration extract and normal culture medium. The viability of the osteoblasts was measured by MTT assay, and the function of the osteoblasts was detected by use of alkaline phosphatase test kit. The locked double-plating (steel plate and HMWP plate) was implanted and fixed at the artificial fracture of distal femur of dogs. Specimens were gained at 3, 6, 9 and 12 weeks postoperatively, examined with macroscopy, microscope and scanning electron microscope (SEM). The results showed that HMWP did no harm to osteoblasts. There is no significant difference in activities of proliferation and alkaline phosphatase between HMWP maceration extract and normal culture medium at each observation time of at 2,4,8, and 14 dyas (P>0. 05). Bone tissue under the implanted HMWP plate manifested no absorption; the new bones formed under the HMWP plate and gradually matured as time went on. It is demonstrated in this study that HMWP has no adverse influence on the viability of osteoblasts and new bone formation and it can be used as internal fixation implant in treating fractures. PMID:16532823

Ren, Gaohong; Lin, Angru; Pei, Guoxian; Hu, Basheng

2006-02-01

191

p27(kip1) deficiency accelerates dentin and alveolar bone formation.  

PubMed

To assess the role of p27(kip1) in regulating dental formation and alveolar bone development, we compared the teeth and mandible phenotypes of homozygous p27(kip1) -deficient (p27(-/-) ) mice with their wild-type littermates at 2 weeks of age. At 2 weeks of age, dental mineral density, dental volume and dentin sialoprotein-immunopositive areas were increased significantly, whereas the predentin area : total dentin area and biglycan-immunopositive area : dentin area ratios were decreased significantly in p27(-/-) mice compared with their wild-type (WT) littermates. Mandible mineral density, cortical thickness, alveolar bone volume, type I collagen and osterix-immunopositive areas, osteoblast number and activity and mRNA expression of Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteocalcin and bone morphogenetic protein (bmp2) were all significantly increased in the mandibles, as was the number and surface of tartrate-resistant acid phosphatase-positive osteoclasts in the alveolar bone of p27(-/-) mice compared with their WT littermates. Furthermore, the percentage of proliferating cell nuclear antigen-positive cells in Hertwig's epithelial root sheath and protein expression of cyclin E and cyclin-dependent kinase 2 were increased significantly in p27(-/-) mice relative to their WT littermates. The results from this study indicate that p27 plays a negative regulatory role in dentin formation and alveolar bone development. PMID:24916068

Yin, Ying; Wang, Qun; Sun, Wen; Wang, Yuli; Chen, Ning; Miao, Dengshun

2014-10-01

192

The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formation  

PubMed Central

Mineralization is a ubiquitous process in the animal kingdom and is fundamental to human development and health. Dysfunctional or aberrant mineralization leads to a variety of medical problems, and so an understanding of these processes is essential to their mitigation. Osteoblasts create the nano-composite structure of bone by secreting a collagenous extracellular matrix (ECM) on which apatite crystals subsequently form. However, despite their requisite function in building bone and decades of observations describing intracellular calcium phosphate, the precise role osteoblasts play in mediating bone apatite formation remains largely unknown. To better understand the relationship between intracellular and extracellular mineralization, we combined a sample-preparation method that simultaneously preserved mineral, ions, and ECM with nano-analytical electron microscopy techniques to examine osteoblasts in an in vitro model of bone formation. We identified calcium phosphate both within osteoblast mitochondrial granules and intracellular vesicles that transported material to the ECM. Moreover, we observed calcium-containing vesicles conjoining mitochondria, which also contained calcium, suggesting a storage and transport mechanism. Our observations further highlight the important relationship between intracellular calcium phosphate in osteoblasts and their role in mineralizing the ECM. These observations may have important implications in deciphering both how normal bone forms and in understanding pathological mineralization. PMID:22879397

Boonrungsiman, Suwimon; Gentleman, Eileen; Carzaniga, Raffaella; Evans, Nicholas D.; McComb, David W.; Porter, Alexandra E.; Stevens, Molly M.

2012-01-01

193

mTORC2 Signaling Promotes Skeletal Growth and Bone Formation in Mice  

PubMed Central

Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase controlling many physiological processes in mammals. mTOR functions in two distinct protein complexes, namely mTORC1 and mTORC2. Compared to mTORC1, the specific roles of mTORC2 are less well understood. To investigate the potential contribution of mTORC2 to skeletal development and homeostasis, we have genetically deleted Rictor, an essential component of mTORC2, in the limb skeletogenic mesenchyme of the mouse embryo. Loss of Rictor leads to shorter and narrower skeletal elements in both embryos and postnatal mice. In the embryo, Rictor deletion reduces the width but not the length of the initial cartilage anlage. Subsequently, the embryonic skeletal elements are shortened due to a delay in chondrocyte hypertrophy, with no change in proliferation, apoptosis, cell size, or matrix production. Postnatally, Rictor-deficient mice exhibit impaired bone formation, resulting in thinner cortical bone, but the trabecular bone mass is relatively normal thanks to a concurrent decrease in bone resorption. Moreover, Rictor-deficient bones exhibit a lesser anabolic response to mechanical loading. Thus, mTORC2 signaling is necessary for optimal skeletal growth and bone anabolism. PMID:25196701

Chen, Jianquan; Holguin, Nilsson; Shi, Yu; Silva, Matthew J.; Long, Fanxin

2015-01-01

194

Reduced bone formation in non-steroid treated patients with rheumatoid arthritis.  

PubMed

The cellular basis of trabecular bone loss in rheumatoid arthritis was investigated in 45 non-steroid treated patients. Mean wall thickness, an indicator of the amount of bone formed per remodelling unit, mean interstitial bone thickness, which is related to resorption depth, and the extent of trabecular surface covered by osteoid, which reflects the number of remodelling units, were assessed in iliac crest biopsy specimens. The mean wall thickness was significantly reduced in the patient group when compared with controls matched for age and sex (mean (SD) 39.8 (5.4) v 51.6 (9.7) microns). There was no significant difference between patients and controls in the mean interstitial bone thickness (51.0 (26.4) v 61.4 (31.9) microns) or osteoid surface (16.7 (11.4) v 21.0 (10.5)%). These results show that reduced bone formation at the remodelling unit level is the predominant mechanism of bone loss in rheumatoid arthritis. PMID:2742402

Compston, J E; Vedi, S; Mellish, R W; Croucher, P; O'Sullivan, M M

1989-06-01

195

Lamellar Icthyosis – A case Report  

PubMed Central

Autosomal recessive congenital ichthyosis is a heterogenous group of disorders that are present at birth with generalized involvement of skin and lack of other organ systems. Clinical presentation, pattern of inheritance, and laboratory evaluation may establish a precise diagnosis, which can assist in prognosis and genetic counseling. There is a little knowledge about the oral manifestations of these disorders.This case report presents management and complete oral rehabilitation of a rare case of lamellar ichthyosis. PMID:25584329

B.V, Thimma Reddy; V, Daneswari; Deshmukh, Sudhanwan N

2014-01-01

196

Pyk2 regulates megakaryocyte-induced increases in osteoblast number and bone formation.  

PubMed

Preclinical and clinical evidence from megakaryocyte (MK)-related diseases suggests that MKs play a significant role in maintaining bone homeostasis. Findings from our laboratories reveal that MKs significantly increase osteoblast (OB) number through direct MK-OB contact and the activation of integrins. We, therefore, examined the role of Pyk2, a tyrosine kinase known to be regulated downstream of integrins, in the MK-mediated enhancement of OBs. When OBs were co-cultured with MKs, total Pyk2 levels in OBs were significantly enhanced primarily because of increased Pyk2 gene transcription. Additionally, p53 and Mdm2 were both decreased in OBs upon MK stimulation, which would be permissive of cell cycle entry. We then demonstrated that OB number was markedly reduced when Pyk2-/- OBs, as opposed to wild-type (WT) OBs, were co-cultured with MKs. We also determined that MKs inhibit OB differentiation in the presence and absence of Pyk2 expression. Finally, given that MK-replete spleen cells from GATA-1-deficient mice can robustly stimulate OB proliferation and bone formation in WT mice, we adoptively transferred spleen cells from these mice into Pyk2-/- recipient mice. Importantly, GATA-1-deficient spleen cells failed to stimulate an increase in bone formation in Pyk2-/- mice, suggesting in vivo the important role of Pyk2 in the MK-induced increase in bone volume. Further understanding of the signaling pathways involved in the MK-mediated enhancement of OB number and bone formation will facilitate the development of novel anabolic therapies to treat bone loss diseases. PMID:23362087

Cheng, Ying-Hua; Hooker, R Adam; Nguyen, Khanh; Gerard-O'Riley, Rita; Waning, David L; Chitteti, Brahmananda R; Meijome, Tomas E; Chua, Hui Lin; Plett, Artur P; Orschell, Christie M; Srour, Edward F; Mayo, Lindsey D; Pavalko, Fredrick M; Bruzzaniti, Angela; Kacena, Melissa A

2013-06-01

197

Inhibition of apoptosis signal-regulating kinase 1 enhances endochondral bone formation by increasing chondrocyte survival.  

PubMed

Endochondral ossification is the result of chondrocyte differentiation, hypertrophy, death and replacement by bone. The careful timing and progression of this process is important for normal skeletal bone growth and development, as well as fracture repair. Apoptosis Signal-Regulating Kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK), which is activated by reactive oxygen species and other cellular stress events. Activation of ASK1 initiates a signaling cascade known to regulate diverse cellular events including cytokine and growth factor signaling, cell cycle regulation, cellular differentiation, hypertrophy, survival and apoptosis. ASK1 is highly expressed in hypertrophic chondrocytes, but the role of ASK1 in skeletal tissues has not been investigated. Herein, we report that ASK1 knockout (KO) mice display alterations in normal growth plate morphology, which include a shorter proliferative zone and a lengthened hypertrophic zone. These changes in growth plate dynamics result in accelerated long bone mineralization and an increased formation of trabecular bone, which can be attributed to an increased resistance of terminally differentiated chondrocytes to undergo cell death. Interestingly, under normal cell culture conditions, mouse embryonic fibroblasts (MEFs) derived from ASK1 KO mice show no differences in either MAPK signaling or osteogenic or chondrogenic differentiation when compared with wild-type (WT) MEFs. However, when cultured with stress activators, H2O2 or staurosporine, the KO cells show enhanced survival, an associated decrease in the activation of proteins involved in death signaling pathways and a reduction in markers of terminal differentiation. Furthermore, in both WT mice treated with the ASK1 inhibitor, NQDI-1, and ASK1 KO mice endochondral bone formation was increased in an ectopic ossification model. These findings highlight a previously unrealized role for ASK1 in regulating endochondral bone formation. Inhibition of ASK1 has clinical potential to treat fractures or to slow osteoarthritic progression by enhancing chondrocyte survival and slowing hypertrophy. PMID:25393478

Eaton, G J; Zhang, Q-S; Diallo, C; Matsuzawa, A; Ichijo, H; Steinbeck, M J; Freeman, T A

2014-01-01

198

Inhibition of apoptosis signal-regulating kinase 1 enhances endochondral bone formation by increasing chondrocyte survival  

PubMed Central

Endochondral ossification is the result of chondrocyte differentiation, hypertrophy, death and replacement by bone. The careful timing and progression of this process is important for normal skeletal bone growth and development, as well as fracture repair. Apoptosis Signal-Regulating Kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK), which is activated by reactive oxygen species and other cellular stress events. Activation of ASK1 initiates a signaling cascade known to regulate diverse cellular events including cytokine and growth factor signaling, cell cycle regulation, cellular differentiation, hypertrophy, survival and apoptosis. ASK1 is highly expressed in hypertrophic chondrocytes, but the role of ASK1 in skeletal tissues has not been investigated. Herein, we report that ASK1 knockout (KO) mice display alterations in normal growth plate morphology, which include a shorter proliferative zone and a lengthened hypertrophic zone. These changes in growth plate dynamics result in accelerated long bone mineralization and an increased formation of trabecular bone, which can be attributed to an increased resistance of terminally differentiated chondrocytes to undergo cell death. Interestingly, under normal cell culture conditions, mouse embryonic fibroblasts (MEFs) derived from ASK1 KO mice show no differences in either MAPK signaling or osteogenic or chondrogenic differentiation when compared with wild-type (WT) MEFs. However, when cultured with stress activators, H2O2 or staurosporine, the KO cells show enhanced survival, an associated decrease in the activation of proteins involved in death signaling pathways and a reduction in markers of terminal differentiation. Furthermore, in both WT mice treated with the ASK1 inhibitor, NQDI-1, and ASK1 KO mice endochondral bone formation was increased in an ectopic ossification model. These findings highlight a previously unrealized role for ASK1 in regulating endochondral bone formation. Inhibition of ASK1 has clinical potential to treat fractures or to slow osteoarthritic progression by enhancing chondrocyte survival and slowing hypertrophy. PMID:25393478

Eaton, G J; Zhang, Q-S; Diallo, C; Matsuzawa, A; Ichijo, H; Steinbeck, M J; Freeman, T A

2014-01-01

199

New perspectives on lamellar keratoplasty.  

PubMed

Lamellar (anterior and posterior) keratoplasty entails the surgical replacement of diseased-only corneal tissue, while healthy host corneal tissue is preserved. Selective keratoplasty offers several advantages in comparison to penetrating keratoplasty such as a lower rate of graft rejection, less endothelial cell loss, faster/superior visual rehabilitation and enhanced resistance to closed injury. The surgical approach of "partial corneal transplantation" may be divided into anterior and posterior: techniques including superficial and deep anterior lamellar keratoplasty (SALK and DALK, respectively) and endothelial keratoplasty as well as Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). These novel surgical procedures are rapidly becoming the preferred therapy option for specific corneal dysfunctions involving the corneal stroma (SALK, DALK), or corneal endothelium (DSAEK, DMEK). During the past decade, the continuing advancement of surgical techniques and the development of innovative surgical instruments have significantly enhanced corneal transplantation. Lamellar keratoplasty techniques facilitate corneal surgery, provide patients with superior outcomes and can successfully restore vision in corneal-related blindness. Nevertheless, more long-term evidence is needed to better evaluate these promising new techniques. PMID:24846543

Kymionis, George D; Mikropoulos, Dimitrios G; Portaliou, Dimitra M; Boboridis, Kostantinos G; Voudouragkaki, Irini C; Dragoumis, Nikolaos D; Konstas, Anastasios G P

2014-05-01

200

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation  

PubMed Central

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 µg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm3, respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls. PMID:21863314

Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy

2012-01-01

201

Insulin-like growth factor I has independent effects on bone matrix formation and cell replication  

SciTech Connect

The effects of insulin-like growth factor-I (IGF-I) and insulin on bone matrix synthesis and bone cell replication were studied in cultured 21-day-old fetal rat calvariae. Histomorphometry techniques were developed to measure the incorporation of (2,3-/sup 3/H)proline and (methyl-/sup 3/H)thymidine into bone matrix and bone cell nuclei, respectively, using autoradiographs of sagittal sections of calvariae cultured with IGF-I, insulin, or vehicle for up to 96 h. To confirm an effect on bone formation, IGF-I was also studied for its effects on (/sup 3/H)proline incorporation into collagenase-digestible protein (CDP) and noncollagen protein and on (/sup 3/H)thymidine incorporation into acid-precipitable material (DNA). IGF-I at 10(-9)-10(-7) M significantly increased the rate of bone matrix apposition and CDP after 24 h by 45-50% and increased cell labeling by 8-fold in the osteoprogenitor cell zone, by 4-fold in the osteoblast cell zone, and by 2-fold in the periosteal fibroblast zone. Insulin at 10(-9)-10(-6) M also increased matrix apposition rate and CDP by 40-50%, but increased cell labeling by 2-fold only at a concentration of 10(-7) M or higher and then only in the osteoprogenitor cell zone. When hydroxyurea was added to IGF-I-treated bones, the effects of IGF-I on DNA synthesis were abolished, but the increase in bone matrix apposition induced by IGF-I was only partly diminished. In conclusion, IGF-I stimulates matrix synthesis in calvariae, an effect that is partly, although not completely, dependent on its stimulatory effect on DNA synthesis.

Hock, J.M.; Centrella, M.; Canalis, E.

1988-01-01

202

Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation  

PubMed Central

Cleft palate, including submucous cleft palate, is among the most common birth defects in humans. While overt cleft palate results from defects in growth or fusion of the developing palatal shelves, submucous cleft palate is characterized by defects in palatal bones. In this report, we show that the Bmpr1a gene, encoding a type I receptor for bone morphogenetic proteins (Bmp), is preferentially expressed in the primary palate and anterior secondary palate during palatal outgrowth. Following palatal fusion, Bmpr1a mRNA expression was upregulated in the condensed mesenchyme progenitors of palatal bone. Tissue-specific inactivation of Bmpr1a in the developing palatal mesenchyme in mice caused reduced cell proliferation in the primary and anterior secondary palate, resulting in partial cleft of the anterior palate at birth. Expression of Msx1 and Fgf10 was downregulated in the anterior palate mesenchyme and expression of Shh was downregulated in the anterior palatal epithelium in the Bmpr1a conditional mutant embryos, indicating that Bmp signaling regulates mesenchymal-epithelial interactions during palatal outgrowth. In addition, formation of the palatal processes of the maxilla was blocked while formation of the palatal processes of the palatine was significantly delayed, resulting in submucous cleft of the hard palate in the mutant mice. Our data indicate that Bmp signaling plays critical roles in the regulation of palatal mesenchyme condensation and osteoblast differentiation during palatal bone formation. PMID:21185278

Baek, Jin-A; Lan, Yu; Liu, Han; Maltby, Kathleen M.; Mishina, Yuji; Jiang, Rulang

2011-01-01

203

Insulin promotes bone formation in augmented maxillary sinus in diabetic rabbits.  

PubMed

The role of insulin during the formation of bone in the augmented space of the maxillary sinus in patients with diabetes is unclear. The authors compared the differences in bone formation after maxillary sinus floor elevation in diabetic and healthy animals and evaluated the effects of insulin on osteogenesis and the differentiation and activities of the osteoblasts. 10 male Japanese white rabbits were divided into two groups after diabetic induction by a single injection of monohydrated alloxan and having maintained steady blood glucose levels. The groups included the diabetes mellitus group (DM; n=5) and the DM+insulin group (n=5); another five healthy rabbits comprised the control group. Maxillary sinus floor elevation was performed by grafting hydroxyapatite particles. Compared with the control group, the newly formed bone area, number of blood vessels and osteoblasts, collagen I content and serum osteocalcin levels were significantly decreased in DM rabbits (P<0.01). Insulin treatment reversed the decrease in bone formation, blood vessels, osteoblasts, collagen I and serum osteocalcin (P<0.01). Insulin treatment also promoted osteogenesis in the augmented space of the diabetic rabbits, which might have resulted from promotion of osteoblast differentiation and upregulation of neovascularization. PMID:22099315

Hou, C-J; Liu, J-L; Li, X; Bi, L-J

2012-03-01

204

Heterotopic Bone Formation Around Vessels: Pilot Study of a New Animal Model  

PubMed Central

Abstract To achieve an easily established, safe, and reproducible animal model for the study of heterotopic bone formation around vessels, a small animal series using New Zealand White rabbits was performed. Three different dosages of recombinant human bone morphogenic protein (rhBMP-2) carried by fibrin matrix were tested. A guided tissue regeneration (GTR) membrane sheet was formed into a tube and allowed to harden; it served both to maintain the space around the vessel bundle and to separate the fibrin matrix with rhBMP-2 from skeletal muscle. Wrapped around the femoral vessel bundle and fixed in place, the tube was filled with the fibrin matrix containing rhBMP-2. The surgical site was closed in layers, and the postoperative healing was uneventful. All animals resumed their full preoperative daily activities 3–4 days after the operation. No adverse events such as wound dehiscence or infection occurred, and all animals could be sacrified at the scheduled date. Micro–computed tomography and histological investigations showed heterotopic bone formation around the vessel bundle in the medium- and high-dosage rhBMP-2 groups. An easy, safe, and reproducible animal model that allows the study of heterotopic bone formation around vessels was successfully established. PMID:23914333

Cai, Wei-Xin; Zheng, Li-Wu; Weber, Franz E.; Li, Chun-Lei; Ma, Li; Ehrbar, Martin

2013-01-01

205

Phosvitin phosphorus is involved in chicken embryo bone formation through dephosphorylation.  

PubMed

The aim of this study was to investigate the role of phosvitin in bone formation in chicken embryos. The yolk P content, P/N ratio and secondary structure of phosvitin, alkaline phosphatase (ALP) activity of the tibia, and body length were determined during incubation. A high correlation was found between the phosphate group content of phosvitin and both secondary structure and bone metabolism (ALP activity in the tibia, body length). The ALP activity and body length growth slightly lagged behind changes in the P/N ratio and the secondary structure of phosvitin. The phosphate content of phosvitin decreased, the ?-random coil and ?-turn gradually transformed into ?-helixes, and the secondary structure of protein tended to become more orderly; these changes mainly occurred on d 13 to 16. Bone formation of the chicken embryos occurred primarily on d 14 to 18, whereas ALP activity and body length growth increased substantially. The results indicate that phosvitin P is involved in chicken embryo bone formation through dephosphorylation. PMID:25352680

Li, Chunyan; Geng, Fang; Huang, Xi; Ma, Meihu; Zhang, Xiaowei

2014-12-01

206

Hypoxia-inducible Factor-1? Protein Negatively Regulates Load-induced Bone Formation*  

PubMed Central

Mechanical loads induce profound anabolic effects in the skeleton, but the molecular mechanisms that transduce such signals are still poorly understood. In this study, we demonstrate that the hypoxia-inducible factor-1? (Hif-1?) is acutely up-regulated in response to exogenous mechanical stimuli secondary to prostanoid signaling and Akt/mTOR (mammalian target of rapamycin) activation. In this context, Hif-1? associates with ?-catenin to inhibit Wnt target genes associated with bone anabolic activity. Mice lacking Hif-1? in osteoblasts and osteocytes form more bone when subjected to tibia loading as a result of increased osteoblast activity. Taken together, these studies indicate that Hif-1? serves as a negative regulator of skeletal mechanotransduction to suppress load-induced bone formation by altering the sensitivity of osteoblasts and osteocytes to mechanical signals. PMID:22081627

Riddle, Ryan C.; Leslie, Julie M.; Gross, Ted S.; Clemens, Thomas L.

2011-01-01

207

ORIGINAL ARTICLE JBMR Unique Roles of Phosphorus in Endochondral Bone Formation and Osteocyte Maturation  

E-print Network

The mechanisms by which inorganic phosphate (Pi) homeostasis controls bone biology are poorly understood. Here we used Dmp1 null mice, a hypophosphatemic rickets/osteomalacia model, combined with a metatarsal organ culture and an application of neutralizing fibroblast growth factor 23 (FGF-23) antibodies to gain insight into the roles of Pi in bone biology. We showed (1) that abnormal bone remodeling in Dmp1 null mice is due to reduced osteoclast number, which is secondary to a reduced ratio of RANKL/OPG expressed by osteoclast supporting cells and (2) that osteoblast extracellular matrix mineralization, growth plate maturation, secondary ossification center formation, and osteoblast differentiation are phosphate-dependent. Finally, a working hypothesis is proposed to explain how

Rong Zhang; Yongbo Lu; Ling Ye; Baozhi Yuan; Shibin Yu; Chunlin Qin; Yixia Xie; Tian Gao; Marc K Drezner; Lynda F Bonewald; Jian Q Feng

208

Evidence for reduced bone formation surface relative to bone resorption surface in female femoral fragility fracture patients  

Microsoft Academic Search

Fragility fractures, including neck of femur fractures, result from reductions in the amount, quality and architecture of bone. The aim of this study was to compare the cancellous bone structure, and static indices of bone turnover, in female patients, who had sustained fragility fracture at the femoral neck, with age-matched females without fragility fracture. Bone samples were taken from the

Helen Tsangari; David M. Findlay; Andrew C. W. Zannettino; Beiqing Pan; Julia S. Kuliwaba; Nicola L. Fazzalari

2006-01-01

209

TWIST1 expression in breast cancer cells facilitates bone metastasis formation.  

PubMed

The transcription factor TWIST1 induces epithelial-mesenchymal transition and/or escape to the oncogenic-induced failsafe program, facilitating the intravasation of breast cancer cells in the systemic circulation and their dissemination to the lungs. Its involvement in breast cancer bone metastasis is unknown. To address this question, human osteotropic MDA-MB-231/B02 breast cancer cells were stably transfected with a Tet-inducible vector encoding for TWIST1, whose expression was specifically repressed in the presence of doxycycline (dox). The intra-arterial inoculation of transfectants expressing TWIST1 in immunodeficient mice substantially increased the extent of osteolytic lesions in these animals, being 50% larger than that of animals bearing mock-transfected tumors, as determined by radiography. This difference was accompanied by a sharp reduction of the bone volume (indicating a higher bone destruction) and a twofold increase in the tumor volume compared with mice bearing mock-transfected tumors, as determined by histomorphometry. Importantly, the suppression of TWIST1 expression in MDA-MB-231/B02 cells in the presence of dox abolished the stimulatory effect of TWIST1 on bone metastasis formation in vivo. Additionally, examination of the bone marrow from untreated and dox-treated animals on day 7 after tumor cell inoculation, at which time there was no evidence of radiographic osteolytic lesions, revealed that the number of tumor cell colonies that were recovered from the bone marrow of untreated mice was dramatically increased compared with that of dox-fed animals. In vitro, TWIST1 expression promoted tumor cell invasion and enhanced microRNA 10b (miR-10b) expression, a proinvasive factor, but was dispensable for growth of tumor cells. In vivo, the repression of miR-10b substantially decreased the presence of TWIST1-expressing breast cancer cells in the bone marrow. Overall, these results establish that TWIST1 facilitates breast cancer bone metastasis formation through a mechanism dependent of miR-10b, which leads to increase tumor burden and bone destruction. PMID:24619707

Croset, Martine; Goehrig, Delphine; Frackowiak, Agnieszka; Bonnelye, Edith; Ansieau, Stéphane; Puisieux, Alain; Clézardin, Philippe

2014-08-01

210

Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse.  

PubMed

Mechanical loading modulates the osteocyte-derived protein sclerostin, a potent inhibitor of bone formation. We hypothesized that simulated resistance training (SRT), combined with alendronate (ALEN) treatment, during hindlimb unloading (HU) would most effectively mitigate disuse-induced decrements in cortical bone geometry and formation rate (BFR). Sixty male, Sprague-Dawley rats (6-mo-old) were randomly assigned to either cage control (CC), HU, HU plus either ALEN (HU+ALEN), or SRT (HU+SRT), or combined ALEN and SRT (HU+SRT/ALEN) for 28 days. Computed tomography scans on days -1 and 28 were taken at the middiaphyseal tibia. HU+SRT and HU+SRT/ALEN rats were subjected to muscle contractions once every 3 days during HU (4 sets of 5 repetitions; 1,000 ms isometric + 1,000 ms eccentric). The HU+ALEN and HU+SRT/ALEN rats received 10 ?g/kg ALEN 3 times/wk. Compared with the CC animals, HU suppressed the normal slow growth-induced increases of cortical bone mineral content, cortical bone area, and polar cross-sectional moment of inertia; however, SRT during HU restored cortical bone growth. HU suppressed middiaphyseal tibia periosteal BFR by 56% vs. CC (P < 0.05). However, SRT during HU restored BFR at both periosteal (to 2.6-fold higher than CC) and endocortical (14-fold higher than CC) surfaces (P < 0.01). ALEN attenuated the SRT-induced BFR gains during HU. The proportion of sclerostin-positive osteocytes in cortical bone was significantly higher (+121% vs. CC) in the HU group; SRT during HU effectively suppressed the higher proportion of sclerostin-positive osteocytes. In conclusion, a minimum number of high-intensity muscle contractions, performed during disuse, restores cortical BFR and suppress unloading-induced increases in sclerostin-positive osteocytes. PMID:22174402

Macias, B R; Swift, J M; Nilsson, M I; Hogan, H A; Bouse, S D; Bloomfield, S A

2012-03-01

211

Use of cultivated osteoprogenitor cells to increase bone formation in segmental mandibular defects: an experimental pilot study in sheep.  

PubMed

The hypothesis of the present experimental pilot study was that autogeneous cultivated osteoprogenitor cells in porous calcium phosphate scaffolds can increase bone formation in segmental defects of the mandible. The autogenous osteoprogenitor cells of eight sheep were cultivated from bone biopsies from the iliac crest and seeded into cylindrical scaffolds of pyrolized bovine bone of an overall length of 35 mm and 13 mm in diameter. Segmental defects of 35 mm length were created unilaterally in the mandibles of the animals. Reconstruction was performed using cylinders with cultivated osteoprogenitor cells in four animals and empty scaffolds in the remaining four sheep, which served as controls. After 5 months, the mandibles were retrieved and the reconstructed areas were analyzed by qualitative and quantitative histology in serial undecalcified thick-section specimens. There was significantly more bone formation in the group that had received scaffolds with cultivated bone cells (P=0.028). Bone formation was present in 34.4% of the evaluated cross-sectional units in the seeded scaffolds, while it was found in 10.4% in the control group. Although the spatial distribution of bone formation was significantly different across the scaffold in both groups, osteoprogenitor cells appeared to have increased bone formation, particularly in the centre of the defect when compared to the control group. It is concluded that the repair of segmental defects of the mandible can be enhanced by the transplantation of autogenous osteoprogenitor cells in a porous calcium phosphate scaffold. PMID:11829236

Schliephake, H; Knebel, J W; Aufderheide, M; Tauscher, M

2001-12-01

212

Bone formation in algae-derived and synthetic calcium phosphates with or without poloxamer.  

PubMed

Calcium phosphate ceramics such as hydroxyapatite (HA) and biphasic calcium phosphates are used clinically to repair bone defects. These calcium phosphate ceramics can differ by composition, structure, and rate of degradation. This study compared 3 calcium phosphate ceramics, 2 of which have similar structure but different composition: 100% HA (algae derived) and HA/?-tricalcium phosphate (?-TCP) 20/80 (algae derived), and 2 with different structure but similar composition: HA/?-TCP 20/80 (algae derived) and HA/?-TCP 15/85 (synthetic). Calcium phosphate ceramics can be difficult to handle and contour during the surgeries. To improve handling, Poloxamer 407 (P407) was added to the 3 ceramics, and its effect on bone healing was also assessed. Bilateral calvarial defects created in the parietal bones of New Zealand white rabbits were left unfilled or were filled with autograft or one of the ceramics, with and without P407. Six weeks after operation, healing was evaluated qualitatively by histology and quantitatively by micro-computed tomography analysis and histomorphometry. All 3 calcium phosphate ceramics demonstrated osteoconductivity and performed similarly in supporting new bone formation, suggesting that the differences in their composition, structure, or degradation did not significantly affect their ability to promote bone healing in this application. Incorporating P407 did not impede osteoconductivity as HA and biphasic calcium phosphate combined with P407 performed similarly as when used alone for craniofacial defect repair. PMID:23524692

Zhou, Aileen Jing-Jing; Clokie, Cameron Malcolm Lang; Peel, Sean Alexander Fitzgerald

2013-03-01

213

Cancellous bone formation response to simulated resistance training during disuse is blunted by concurrent alendronate treatment.  

PubMed

The purpose of this study was to assess the effectiveness of simulated resistance training (SRT) exercise combined with alendronate (ALEN) in mitigating or preventing disuse-associated losses in cancellous bone microarchitecture and formation. Sixty male Sprague-Dawley rats (6 months old) were randomly assigned to either cage control (CC), hind limb unloading (HU), HU plus either ALEN (HU?+?ALEN), SRT (HU?+?SRT), or a combination of ALEN and SRT (HU?+?SRT/ALEN) for 28 days. HU?+?SRT and HU?+?SRT/ALEN rats were anesthetized and subjected to muscle contractions once every 3 days during HU (four sets of five repetitions, 1000?ms isometric?+?1000?ms eccentric). Additionally, HU?+?ALEN and HU?+?SRT/ALEN rats received 10?µg/kg of body weight of ALEN three times per week. HU reduced cancellous bone-formation rate (BFR) by 80%, with no effect of ALEN treatment (-85% versus CC). SRT during HU significantly increased cancellous BFR by 123% versus CC, whereas HU?+?SRT/ALEN inhibited the anabolic effect of SRT (-70% versus HU?+?SRT). SRT increased bone volume and trabecular thickness by 19% and 9%, respectively, compared with CC. Additionally, osteoid surface (OS/BS) was significantly greater in HU?+?SRT rats versus CC (+32%). Adding ALEN to SRT during HU reduced Oc.S/BS (-75%), Ob.S/BS (-72%), OS/BS (-61%), and serum TRACP5b (-36%) versus CC. SRT and ALEN each independently suppressed a nearly twofold increase in adipocyte number evidenced with HU and inhibited increases in osteocyte apoptosis. These results demonstrate the anabolic effect of a low volume of high-intensity muscle contractions during disuse and suggest that both bone resorption and bone formation are suppressed when SRT is combined with bisphosphonate treatment. PMID:21509821

Swift, Joshua M; Swift, Sibyl N; Nilsson, Mats I; Hogan, Harry A; Bouse, Scott D; Bloomfield, Susan A

2011-09-01

214

Twist1- and Twist2-Haploinsufficiency Results in Reduced Bone Formation  

PubMed Central

Background Twist1 and Twist2 are highly homologous bHLH transcription factors that exhibit extensive highly overlapping expression profiles during development. While both proteins have been shown to inhibit osteogenesis, only Twist1 haploinsufficiency is associated with the premature synostosis of cranial sutures in mice and humans. On the other hand, biallelic Twist2 deficiency causes only a focal facial dermal dysplasia syndrome or additional cachexia and perinatal lethality in certain mouse strains. It is unclear how these proteins cooperate to synergistically regulate bone formation. Methods Twist1 floxed mice (Twist1f/f) were bred with Twist2-Cre knock-in mice (Twist2Cre/+) to generate Twist1 and Twist2 haploinsufficient mice (Twist1f/+; Twist2Cre/+). X-radiography, micro-CT scans, alcian blue/alizarin red staining, trap staining, BrdU labeling, immunohistochemistry, in situ hybridizations, real-time PCR and dual luciferase assay were employed to investigate the overall skeletal defects and the bone-associated molecular and cellular changes of Twist1f/+;Twist2Cre/+ mice. Results Twist1 and Twist2 haploinsufficient mice did not present with premature ossification and craniosynostosis; instead they displayed reduced bone formation, impaired proliferation and differentiation of osteoprogenitors. These mice exhibited decreased expressions of Fgf2 and Fgfr1–4 in bone, resulting in a down-regulation of FGF signaling. Furthermore, in vitro studies indicated that both Twist1 and Twist2 stimulated 4.9 kb Fgfr2 promoter activity in the presence of E12, a Twist binding partner. Conclusion These data demonstrated that Twist1- and Twist2-haploinsufficiency caused reduced bone formation due to compromised FGF signaling. PMID:24971743

Huang, Yanyu; Meng, Tian; Wang, Suzhen; Zhang, Hua; Mues, Gabriele; Qin, Chunlin; Feng, Jian Q.; D'Souza, Rena N.; Lu, Yongbo

2014-01-01

215

Exercise and Mechanical Loading Increase Periosteal Bone Formation and Whole Bone Strength in C57BL\\/6J Mice but Not in C3H\\/Hej Mice  

Microsoft Academic Search

.   To identify the genes, and the mechanisms that account for the 53% higher peak bone density in C3H\\/HeJ (C3H) mice compared\\u000a with C57BL\\/6J (B6) mice, we are performing quantitative trait locus and phenotypic analyses. The phenotypic studies revealed\\u000a differences in bone formation and resorption, and showed that hindlimb immobilization (by sciatic neurectomy) caused a greater\\u000a increase in endosteal resorption

Y. Kodama; Y. Umemura; S. Nagasawa; W. G. Beamer; L. R. Donahue; C. R. Rosen; D. J. Baylink; J. R. Farley

2000-01-01

216

Vitamin E stimulates trabecular bone formation and alters epiphyseal cartilage morphometry  

Microsoft Academic Search

The effects of dietary vitamin E (VIT E) and lipids on tissue lipid peroxidation and fatty acid composition, epiphyseal growth plate cartilage development, and trabecular bone formation were evaluated in chicks. A 2×2 factorial design was followed using two levels (30 and 90 IU\\/kg of diet) of dl-?-tocopheryl acetate and two different dietary lipids. The basal semipurified diet contained one

H. Xu; B. A. Watkins; M. F. Seifert

1995-01-01

217

Hydroxyapatite bioactivated bacterial cellulose promotes osteoblast growth and the formation of bone nodules.  

PubMed

The goal of this study was to investigate the feasibility of bacterial cellulose (BC) scaffold to support osteoblast growth and bone formation. BC was produced by culturing Acetobacter xylinum supplemented with hydroxyapatite (HA) to form BC membranes (without HA) and BC/HA membranes. Membranes were subjected to X-ray photoelectron spectroscopy (XPS) analysis to determine surface element composition. The membranes were further used to evaluate osteoblast growth, alkaline phosphatase activity and bone nodule formation. BC was free of calcium and phosphate. However, XPS analysis revealed the presence of both calcium (10%) and phosphate (10%) at the surface of the BC/HA membrane. Osteoblast culture showed that BC alone was non-toxic and could sustain osteoblast adhesion. Furthermore, osteoblast adhesion and growth were significantly (p ?0.05) increased on BC/HA membranes as compared to BC alone. Both BC and BC/HA membranes improved osteoconductivity, as confirmed by the level of alkaline phosphatase (ALP) activity that increased from 2.5 mM with BC alone to 5.3 mM with BC/HA. BC/HA membranes also showed greater nodule formation and mineralization than the BC membrane alone. This was confirmed by Alizarin red staining (ARS) and energy dispersive X-ray spectroscopy (EDX). This work demonstrates that both BC and BC/HA may be useful in bone tissue engineering. PMID:23174338

Tazi, Neftaha; Zhang, Ze; Messaddeq, Younès; Almeida-Lopes, Luciana; Zanardi, Lisinéia M; Levinson, Dennis; Rouabhia, Mahmoud

2012-01-01

218

Hydroxyapatite bioactivated bacterial cellulose promotes osteoblast growth and the formation of bone nodules  

PubMed Central

The goal of this study was to investigate the feasibility of bacterial cellulose (BC) scaffold to support osteoblast growth and bone formation. BC was produced by culturing Acetobacter xylinum supplemented with hydroxyapatite (HA) to form BC membranes (without HA) and BC/HA membranes. Membranes were subjected to X-ray photoelectron spectroscopy (XPS) analysis to determine surface element composition. The membranes were further used to evaluate osteoblast growth, alkaline phosphatase activity and bone nodule formation. BC was free of calcium and phosphate. However, XPS analysis revealed the presence of both calcium (10%) and phosphate (10%) at the surface of the BC/HA membrane. Osteoblast culture showed that BC alone was non-toxic and could sustain osteoblast adhesion. Furthermore, osteoblast adhesion and growth were significantly (p ?0.05) increased on BC/HA membranes as compared to BC alone. Both BC and BC/HA membranes improved osteoconductivity, as confirmed by the level of alkaline phosphatase (ALP) activity that increased from 2.5 mM with BC alone to 5.3 mM with BC/HA. BC/HA membranes also showed greater nodule formation and mineralization than the BC membrane alone. This was confirmed by Alizarin red staining (ARS) and energy dispersive X-ray spectroscopy (EDX). This work demonstrates that both BC and BC/HA may be useful in bone tissue engineering. PMID:23174338

2012-01-01

219

Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties  

Microsoft Academic Search

Sixteen patients (18 hips) were treated with localized radiation therapy limited to periarticular regions surrounding the femoral neck by shielding the prosthesis and the adjacent regions to prevent heterotopic bone formation around the uncemented prosthesis. All hips received 1500 rads. Eight of these hips were irradiated after excising severe heterotopic bone, five because they developed extensive heterotopic ossification in the

MURALI JASTY; STEVEN SCHUTZER; JOEL TEPPER; CHRISTOPHER WILLETT; MICHAEL A. STRACHER; WILLIAM H. HARRIS

1990-01-01

220

Efficiently engineered cell sheet using a complex of polyethylenimine–alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation  

PubMed Central

Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine–alginate (PEI–al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI–al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI–al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration. PMID:24855355

Jin, Han; Zhang, Kai; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Zheng, Changyu; Liu, Xiaohua; Yang, Bai; Sun, Hongchen

2014-01-01

221

Hierarchy of Bone Microdamage at Multiple Length Scales  

PubMed Central

Microdamage formation is a critical determinant of bone fracture and the nature and type of damage formed in bone depends on the interaction of its extracellular matrix (ECM) with the applied loading. More importantly, because bone is a hierarchical composite with multiple length scales linked to each other, the nature and type of damage in bone could also be hierarchical. In this review article, based on new unpublished data and a reanalysis of literature reports on in vivo and in vitro observations of microdamage, three length scales including mineralized collagen fibrils, lamellar and osteonal levels have been identified as the key contributors to microdamage hierarchy and energy dissipation in bone. Inherent hierarchy in bone’s ECM therefore has specific microstructural features and energy dissipation mechanisms at different length scales that allow the bone to effectively resist the different components of the applied physiological loading. Furthermore, because human bones experience multiaxial cyclic loading and its ECM is subjected to variation with aging and disease, additional emphasis is placed on investigating how the nature of applied loading and the quality of ECM affect the hierarchy of microdamage formation with age. PMID:18516216

Vashishth, Deepak

2007-01-01

222

Flap complications associated with lamellar refractive surgery  

Microsoft Academic Search

PURPOSE: Corneal lamellar refractive surgery for myopia reduces the risk of corneal haze but adds to the risk of flap complications. We retrospectively determined the incidence of flap complications in the initial series of eyes undergoing lamellar refractive surgery by one surgeon. We assessed the incidence of flap complications overall, the trend in these complications during the surgeon’s learning curve,

Robert T Lin; Robert K Maloney

1999-01-01

223

Changes in markers of bone formation and resorption in a bed rest model of weightlessness  

NASA Technical Reports Server (NTRS)

To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

Lueken, S. A.; Arnaud, S. B.; Taylor, A. K.; Baylink, D. J.

1993-01-01

224

Sequential Application of Steady and Pulsatile Medium Perfusion Enhanced the Formation of Engineered Bone  

PubMed Central

In native bone, cells experience fluctuating shear forces that are induced by pulsatile interstitial flow associated with habitual loading. We hypothesized that the formation of engineered bone can be augmented by replicating such physiologic stimuli to osteogenic cells cultured in porous scaffolds using bioreactors with medium perfusion. To test this hypothesis, we investigated the effect of fluid flow regime on in vitro bone-like tissue development by human adipose stem cells (hASC) cultivated on porous three-dimensional silk fibroin scaffolds. To this end, we varied the sequential relative durations of steady flow (SF) and pulsatile flow (PF) of culture medium applied over a period of 5 weeks, and evaluated their effect on early stages of bone formation. Porous silk fibroin scaffolds (400–600??m pore size) were seeded with hASC (30×106 cells/mL) and cultured in osteogenic medium under four distinct fluid flow regimes: (1) PF for 5 weeks; (2) SF for 1 week, PF for 4 weeks; (3) SF for 2 weeks, PF for 3 weeks; (4) SF for 5 weeks. The PF was applied in 12?h intervals, with the interstitial velocity fluctuating between 400 and 1200??m/s at a 0.5?Hz frequency for 2?h, followed by 10?h of SF. In all groups, SF was applied at 400??m/s. The best osteogenic outcomes were achieved for the sequence of 2 weeks of SF and 3 weeks of PF, as evidenced by gene expression (including the PGE2 mechanotransduction marker), construct compositions, histomorphologies, and biomechanical properties. We thus propose that osteogenesis in hASC and the subsequent early stage bone development involve a mechanism, which detects and responds to the level and duration of hydrodynamic shear forces. PMID:23259605

Correia, Cristina; Bhumiratana, Sarindr; Sousa, Rui A.; Reis, Rui L.

2013-01-01

225

Production of New Trabecular Bone in Osteopenic Ovariectomized Rats by Prostaglandin E2  

NASA Technical Reports Server (NTRS)

Serum chemistry and bone morphometry of the proximal tibial metaphysis were performed in 3 month-old double fluorescent-labeled, female Sprague-Dawley rats subjected to bilateral ovariectomy or sham surgery for 4 months prior to treatment with 0, 0.3, 1,3, or 6 mg of prostaglandin E2 (PGE2)/kg/day subcutaneously for 30 days. The 4 month postovariectomized rats possessed an osteopenic proximal tibial metaphysis with 7% trabecular area compared with controls (19%). PGE2 treatment elevated osteocalcin levels and augmented proximal tibial metaphyseal bone area in ovariectomized and sham-operated rats. Osteopenic, ovariectomized rats treated with 6 mg (PGE2)/kg/day for 30 days restored bone area to levels of agematched sham-operated rats. Morphometric analyses showed increased woven and lamellar bone area, fluorescent-labeled perimeter (osteoblastic recruitment), mineral apposition rate (osteoblastic activity), bone formation rate (BFR/BV), and longitudinal bone growth. These dramatic bone changes were all significantly increased at the doseresponse manner. This study showed that in vivo PGE2 is a powerful activator of bone remodeling, it increases both bone resorption and bone formation, and produces an anabolic effect by shifting bone balance to the positive direction. Furthermore, PGE2-induced augmentation of metaphyseal bone area in ovariectomized rats was at least two times greater than in sham-operated rats.

Mori, S.; Jee, W. S. S.; Li, X. J.

1992-01-01

226

EPO promotes bone repair through enhanced cartilaginous callus formation and angiogenesis.  

PubMed

Erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-? (HIF-?) pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14). In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration. PMID:25003898

Wan, Lin; Zhang, Fengjie; He, Qiling; Tsang, Wing Pui; Lu, Li; Li, Qingnan; Wu, Zhihong; Qiu, Guixing; Zhou, Guangqian; Wan, Chao

2014-01-01

227

EPO Promotes Bone Repair through Enhanced Cartilaginous Callus Formation and Angiogenesis  

PubMed Central

Erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-? (HIF-?) pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14). In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration. PMID:25003898

Wan, Lin; Zhang, Fengjie; He, Qiling; Tsang, Wing Pui; Lu, Li; Li, Qingnan; Wu, Zhihong; Qiu, Guixing; Zhou, Guangqian; Wan, Chao

2014-01-01

228

Light-sensitive lamellar phases.  

PubMed

Light sensitive lamellar (L(alpha)) phases have been generated in glycerol/water mixtures from blends of an inert ABA tri-block co-polymer (dimethylsiloxane-polyethylenoxide, (EO)(15)-(PDMS)(15)-(EO)(15)), and a photodestructible anionic surfactant C(6)PAS (sodium 4-hexylphenylazosulfonate). These L(alpha) systems have been formulated in a 6/4 glycerol/water (v/v) mixed solvent. Rheology, small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS) and dynamic light scattering (DLS) have been used to characterize the change in phase behavior and structure after the incorporated C(6)PAS is selectively degraded by UV light incident on the L(alpha) phases. The ABA co-polymer alone forms weakly structured lamellar mesophases, which are stabilized by thermal fluctuations and characterized by low shear moduli (L(alpha) phase-A). Addition of C(6)PAS (10 mM) introduces charge stabilization, generating more ordered and stiffer L(alpha) systems (L(alpha) phase-B). After UV irradiation (Hg lamp) of the L(alpha)-B phases, and subsequent degradation of the ionic C(6)PAS, the results of rheological and scattering studies are consistent with an irreversible change back to L(alpha) phase-A type systems. These formulations display a novel transition between electrostatically- and thermally-stabilized lamellae, which may be controlled by incident UV light. PMID:18407285

Zou, Aihua; Eastoe, Julian; Mutch, Kevin; Wyatt, Paul; Scherf, Günther; Glatter, Otto; Grillo, Isabelle

2008-06-15

229

In vivo formation of bone and haematopoietic territories by transplanted human bone marrow stromal cells generated in medium with and without osteogenic supplements.  

PubMed

Autologous transplantation of human bone marrow stromal cells (BMSCs) has been successfully used for bone reconstruction. However, in order to advance this approach into the mainstream of bone tissue engineering, the conditions for BMSC cultivation and transplantation must be optimized. In a recent report, cultivation with dexamethasone (Dex) significantly increased bone formation by human BMSCs in vivo. Based on this important conclusion, we analysed the data accumulated by our laboratory, where human BMSCs have been routinely generated using media both with and without a combination of two osteogenic supplements: Dex at 10(-8) ?m and ascorbic acid phosphate (AscP) at 10(-4) ?m. Our data demonstrate that for 22/24 donors, BMSC strains propagated with and without Dex/AscP formed similar amounts of bone in vivo. Thus, human BMSCs do not appear to need to be induced to osteogenic differentiation ex vivo prior to transplantation. Similarly, for 12/14 donors, BMSC strains cultured with and without Dex/AscP formed haematopoietic territories to a comparable extent. While Dex/AscP did not increase bone formation, they significantly stimulated BMSC in vitro proliferation without affecting the number of BMSC colonies formed by the colony-forming units-fibroblasts. We conclude that for the substantial majority of donors, Dex/AscP have no effect on the ability of BMSCs to form bone and myelosupportive stroma in vivo. However, due to increased BMSC proliferation, the total osteogenic population obtained from a single marrow sample is larger after cultivation with Dex/AscP than without them. Secondary to increased BMSC proliferation, Dex/AscP may stimulate bone formation if BMSCs and/or the transplantation system are less than optimal. Published 2011. This article is a U.S. Government work and is in the public domain in the USA. PMID:22052864

Kuznetsov, Sergei A; Mankani, Mahesh H; Robey, Pamela Gehron

2013-03-01

230

Copal bone cement is more effective in preventing biofilm formation than Palacos R-G.  

PubMed

Bone cements loaded with combinations of antibiotics are assumed more effective in preventing infection than bone cements with gentamicin as a single drug. Moreover, loading with an additional antibiotic may increase interconnectivity between antibiotic particles to enhance release. We hypothesize addition of clindamycin to a gentamicin-loaded cement yields higher antibiotic release and causes larger inhibition zones against clinical isolates grown on agar and stronger biofilm inhibition. Antibiotic release after 672 hours from Copal bone cement was more extensive (65% of the clindamycin and 41% of the gentamicin incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The higher antibiotic release from Copal resulted in a stronger and more prolonged inhibition of bacterial growth on agar. Bacterial colony counting and confocal laser scanning microscopy of biofilms grown on the bone cements suggest antibiotic release reduced bacterial viability, most notably close to the cement surface. The gentamicin-sensitive Staphylococcus aureus formed gentamicin-resistant small colony variants on Palacos R-G and therefore Copal more effectively decreased biofilm formation than Palacos R-G. PMID:18338216

Ensing, Geert T; van Horn, Jim R; van der Mei, Henny C; Busscher, Henk J; Neut, Daniëlle

2008-06-01

231

Copal Bone Cement Is More Effective in Preventing Biofilm Formation than Palacos R-G  

PubMed Central

Bone cements loaded with combinations of antibiotics are assumed more effective in preventing infection than bone cements with gentamicin as a single drug. Moreover, loading with an additional antibiotic may increase interconnectivity between antibiotic particles to enhance release. We hypothesize addition of clindamycin to a gentamicin-loaded cement yields higher antibiotic release and causes larger inhibition zones against clinical isolates grown on agar and stronger biofilm inhibition. Antibiotic release after 672 hours from Copal bone cement was more extensive (65% of the clindamycin and 41% of the gentamicin incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The higher antibiotic release from Copal resulted in a stronger and more prolonged inhibition of bacterial growth on agar. Bacterial colony counting and confocal laser scanning microscopy of biofilms grown on the bone cements suggest antibiotic release reduced bacterial viability, most notably close to the cement surface. The gentamicin-sensitive Staphylococcus aureus formed gentamicin-resistant small colony variants on Palacos R-G and therefore Copal more effectively decreased biofilm formation than Palacos R-G. PMID:18338216

Ensing, Geert T.; van Horn, Jim R.; van der Mei, Henny C.; Busscher, Henk J.

2008-01-01

232

Local inhibition of 5-lipoxygenase enhances bone formation in a rat model  

PubMed Central

Objectives Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis. Methods Bilateral, unicortical femoral defects were used in rats to measure the effects of local 5-LO inhibition on direct osteogenesis. The defect sites were filled with a polycaprolactone (PCL) scaffold containing 5-LO inhibitor (A-79175) at three dose levels, scaffold with drug carrier, or scaffold only. Drug release was assessed in vitro. Osteogenesis was assessed by micro-CT and histology at two endpoints of ten and 30 days. Results Using micro-CT, we found that A-79175, a 5-LO inhibitor, increased bone formation in an apparent dose-related manner. Conclusions These results indicate that 5-LO inhibition could be used therapeutically to enhance treatments that require the direct formation of bone. PMID:23610701

Cottrell, J. A.; Keshav, V.; Mitchell, A.; O’Connor, J. P.

2013-01-01

233

Kartogenin induces cartilage-like tissue formation in tendon–bone junction  

PubMed Central

Tendon–bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs. PMID:25419468

Zhang, Jianying; Wang, James H-C

2014-01-01

234

Eldecalcitol improves mechanical strength of cortical bones by stimulating the periosteal bone formation in the senescence-accelerated SAM/P6 mice - a comparison with alfacalcidol.  

PubMed

Eldecalcitol (ELD), a 2?-hydroxypropyloxy derivative of 1?,25(OH)2D3, is a potent inhibitor of bone resorption that has demonstrated a greater effect at reducing the risk of fracture in osteoporotic patients than alfacalcidol (ALF). In the present study, we used the senescence-accelerated mouse strain P6 (SAM/P6), which has low bone mass caused by osteoblast dysfunction, to evaluate the effect of ELD on cortical bone in comparison with ALF. Four-month-old SAM/P6 mice were given either ELD (0.025 or 0.05?g/kg) or ALF (0.2 or 0.4?g/kg) by oral gavage 5 times/week for 6 weeks. Both ELD and ALF increased serum calcium (Ca) in a dose-dependent manner. Serum Ca levels in the ELD 0.05?g/kg group were comparable to those of the ALF 0.2?g/kg group. ELD 0.05?g/kg significantly improved the bone biomechanical properties of the femur compared with the vehicle control group (p<0.001) and the ALF 0.2?g/kg group (p<0.05) evaluated by 3-point bending test. The cortical area of the mid-femur in the ELD 0.05?g/kg group but not the ALF 0.2?g/kg group was significantly higher than those of the vehicle control group (p<0.001). Bone histomorphometry revealed that in the femoral endocortical surface, the suppression of bone resorption parameters (N.Oc/BS) and bone formation parameters (MS/BS) by ELD (0.05?g/kg) was greater than that by ALF (0.2?g/kg). In contrast, in the femoral periosteal surface, ELD 0.05?g/kg significantly increased bone formation parameters (BFR/BS, MS/BS) compared with the vehicle control group (p<0.05, p<0.01, respectively), whereas ALF 0.2?g/kg did not alter these parameters. These results indicate that ELD improved the biomechanical properties of femoral cortical bone not only by inhibiting endocortical bone resorption but also by stimulating the periosteal bone formation in SAM/P6 mice. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID:24189542

Shiraishi, Ayako; Sakai, Sadaoki; Saito, Hitoshi; Takahashi, Fumiaki

2014-10-01

235

Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss.  

PubMed

Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day(-1)·rat(-1)) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H(2)O + Sal, H(2)O + 5-FU, EO + 5-FU, and EO + Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H(2)O + 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNF?, osteoclast marker receptor activator of nuclear factor-?B, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss. PMID:22436700

Raghu Nadhanan, Rethi; Abimosleh, Suzanne M; Su, Yu-Wen; Scherer, Michaela A; Howarth, Gordon S; Xian, Cory J

2012-06-01

236

Updating the Lamellar Hypothesis of Hippocampal Organization  

PubMed Central

Andersen et al. (1971) proposed that excitatory activity in the entorhinal cortex propagates topographically to the dentate gyrus, and on through a “trisynaptic circuit” lying within transverse hippocampal “slices” or “lamellae.” In this way, a relatively simple structure might mediate complex functions in a manner analogous to the way independent piano keys can produce a nearly infinite variety of unique outputs. The lamellar hypothesis derives primary support from the “lamellar” distribution of dentate granule cell axons (the mossy fibers), which innervate dentate hilar neurons and area CA3 pyramidal cells and interneurons within the confines of a thin transverse hippocampal segment. Following the initial formulation of the lamellar hypothesis, anatomical studies revealed that unlike granule cells, hilar mossy cells, CA3 pyramidal cells, and Layer II entorhinal cells all form axonal projections that are more divergent along the longitudinal axis than the clearly “lamellar” mossy fiber pathway. The existence of pathways with “translamellar” distribution patterns has been interpreted, incorrectly in our view, as justifying outright rejection of the lamellar hypothesis (Amaral and Witter, 1989). We suggest that the functional implications of longitudinally projecting axons depend not on whether they exist, but on what they do. The observation that focal granule cell layer discharges normally inhibit, rather than excite, distant granule cells suggests that longitudinal axons in the dentate gyrus may mediate “lateral” inhibition and define lamellar function, rather than undermine it. In this review, we attempt a reconsideration of the evidence that most directly impacts the physiological concept of hippocampal lamellar organization. PMID:23233836

Sloviter, Robert S.; Lømo, Terje

2012-01-01

237

Clonal distribution of osteoprogenitor cells in cultured chick periostea: Functional relationship to bone formation  

SciTech Connect

Folded explants of periosteum from embryonic chick calvaria form bone-like tissue when grown in the presence of ascorbic acid, organic phosphate, and dexamethasone. All osteoblast-like cells in these cultures arise de novo by differentiation of osteoprogenitor cells present in the periosteum. To study the spatial and functional relationships between bone formation and osteoprogenitor cells, cultures were continuously labeled with (3H)thymidine for periods of 1-5 days. Radioautographs of serial 2-microns plastic sections stained for alkaline phosphatase (AP) showed maximal labeling of 30% of fibroblastic (AP-negative) cells by 3 days while osteogenic cells (AP-positive) exhibited over 95% labeling by 5 days. No differential shifts in labeling indices, grain count histograms of fibroblastic and osteogenic cells or numbers of AP-positive cells were observed, indicating no significant recruitment of cells from the fibroblastic to the osteogenic compartment. Despite the continuous presence of (3H)thymidine, less than 35% of both osteoblasts and osteocytes were labeled at 5 days, indicating that only one-third of the osteoprogenitor cells had cycled prior to differentiation. Spatial clustering of (3H)thymidine-labeled cells was measured by computer-assisted morphometry and application of the Poisson distribution to assess contagion. Cluster size and number of labeled cells per cluster did not vary between 1-3 days, but the number of clusters increased 20-fold between Day 1 and Day 3. Three-dimensional reconstruction from serial sections showed that clusters formed long, tubular arrays of osteogenic cells up to eight cells in length and located within 2-3 cell layers from the bone surface. Selective killing of S-phase cells with two pulse labels of high specific activity (3H)thymidine at 1 and 2 days of culture completely blocked bone formation.

McCulloch, C.A.; Fair, C.A.; Tenenbaum, H.C.; Limeback, H.; Homareau, R. (Univ. of Toronto, Ontario (Canada))

1990-08-01

238

Posterior Lamellar Keratoplasty in Perspective  

Microsoft Academic Search

\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Posterior lamellar keratoplasty (PLK) offers many substantial benefits compared to penetrating keratoplasty (PK) including:\\u000a closed eye surgery elimination of both regular and irregular postoperative astigmatism leading to full visual rehabilitation\\u000a with spectacles within 3–6 months, elimination of postoperative corneal anaesthesia, and a reduced risk of postoperative globe\\u000a rupture.\\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Disadvantages of PLK compared to PK include: corneal stromal scarring

F Arnalich-Montiel; JKG Dart

239

Silorane resin supports proliferation, differentiation, and mineralization of MLO-A5 bone cells in vitro and bone formation in vivo.  

PubMed

Methyl methacrylate used in bone cements has drawbacks of toxicity, high exotherm, and considerable shrinkage. A new resin, based on silorane/oxirane chemistry, has been shown to have little toxicity, low exotherm, and low shrinkage. We hypothesized that silorane-based resins may also be useful as components of bone cements as well as other bone applications and began testing on bone cell function in vitro and in vivo. MLO-A5, late osteoblast cells, were exposed to polymerized silorane (SilMix) resin (and a standard polymerized bisGMA/TEGDMA methacrylate (BT) resin and compared to culture wells without resins as control. A significant cytotoxic effect was observed with the BT resin resulting in no cell growth, whereas in contrast, SilMix resin had no toxic effects on MLO-A5 cell proliferation, differentiation, nor mineralization. The cells cultured with SilMix produced increasing amounts of alkaline phosphatase (1.8-fold) compared to control cultures. Compared to control cultures, an actual enhancement of mineralization was observed in the silorane resin-containing cultures at days 10 and 11 as determined by von Kossa (1.8-2.0 fold increase) and Alizarin red staining (1.8-fold increase). A normal bone calcium/phosphate atomic ratio was observed by elemental analysis along with normal collagen formation. When used in vivo to stabilize osteotomies, no inflammatory response was observed, and the bone continued to heal. In conclusion, the silorane resin, SilMix, was shown to not only be non cytototoxic, but actually supported bone cell function. Therefore, this resin has significant potential for the development of a nontoxic bone cement or bone stabilizer. PMID:22278990

Eick, J David; Barragan-Adjemian, Cielo; Rosser, Jennifer; Melander, Jennifer R; Dusevich, Vladimir; Weiler, Rachel A; Miller, Bradley D; Kilway, Kathleen V; Dallas, Mark R; Bi, Lianxing; Nalvarte, Elisabet L; Bonewald, Lynda F

2012-04-01

240

Combination of BMP2 and MSCs Significantly Increases Bone Formation in the Rat Arterio-Venous Loop Model.  

PubMed

Introduction: In this study the induction of bone formation in an axially vascularized bone matrix using mesenchymal stem cells (MSCs) and application of bone morphogenetic protein 2 (BMP2) was analyzed in the arteriovenous loop (AVL) model. Materials and Methods: An AVL was created in the medial thigh of 42 rats and placed in a porous titanium chamber filled with a particulated porous hydroxyapatite and beta-tricalcium phosphate matrix and fibrin. In group A the fibrin was loaded with 5×10(6) DiI-stained fibrin gel-immobilized primary MSCs from syngenic Lewis rats, in group B the matrix was loaded with 60??g/mL BMP2 and in group C both, BMP2 and MSCs were applied at implantation time point. After 6 and 12 weeks, specimens were investigated by means of histological, morphometrical, and micro-computed tomography analysis. Results: After implantation of an AVL a dense vascular network was visible in all groups. In group A, newly generated bone islands were detected in the periphery of the main vascular axis. Using BMP2 alone (group B), small islands of newly formed bone were visible evenly distributed in all parts of the constructs. In group C nearly the whole matrix was interspersed with bone formations. In all groups there was an increase of bone formation between the 6 and 12 weeks explantation time points. Conclusions: This study demonstrates for the first time the successful generation of axially vascularized bone substitutes using MSCs and BMP2 in the AVL rat model using a one step procedure. Using the combination of BMP2 and MSCs there was a significant increase of bone formations detectable compared to the BMP2 or MSCs alone groups. PMID:25135080

Buehrer, Gregor; Balzer, Amelie; Arnold, Isabel; Beier, Justus P; Koerner, Carolin; Bleiziffer, Oliver; Brandl, Andreas; Weis, Christian; Horch, Raymund E; Kneser, Ulrich; Arkudas, Andreas

2014-11-01

241

BMP-2 gene modified canine bMSCs promote ectopic bone formation mediated by a nonviral PEI derivative  

PubMed Central

The study was to explore the effects of BMP-2 gene modified canine bone marrow stromal cells (bMSCs) mediated by a nonviral PEI derivative (GenEscort™ II) in promoting bone formation in vitro and in vivo. Canine bMSCs were cultured and transfected with plasmids containing bone morphogenetic protein-2 gene (pBMP-2) or enhanced green fluorescent protein gene (pEGFP). Gene transfection conditions were initially optimized by varying GenEscort™ II/plasmid ratios. Osteogenic differentiation of gene modified bMSCs was investigated via alkaline phosphatase (ALP) activity analysis and real-time quantitative PCR (RT-qPCR) analysis in vitro. The bone formation ability of pBMP-2 transfected bMSCs combined with apatite-coated silk scaffolds (mSS) was explored and compared with pEGFP transfected bMSCs/mSS or untreated bMSCs/mSS at 8, 12 weeks after operation. Results showed that gene transfection efficiency reached up to 36.67 ± 4.12% as demonstrated by EGFP expression. ALP staining and activity assay were stronger with pBMP-2 gene transfection, and the mRNA expression of BMP-2, bone sialoprotein (BSP), Runt-related transcription factor 2 (Runx-2) and osteopontin (OPN) up-regulated in bMSCs 3, 6, 9 days in pBMP-2 group. Besides, the tissue-engineered bone complex with pBMP-2 modified bMSCs achieved significantly increased de novo bone formation compared with control groups (P<0.01). We conclude that pBMP-2 transfection mediated by GenEscort™ II could enhance the osteogenic differentiation of canine bMSCs and promote the ectopic new bone formation in nude mice. GenEscort™ II mediated pBMP-2 gene transfer appears to be a safe and effective nonviral method for gene enhanced bone tissue engineering. PMID:21347550

Lü, Kaige; Zeng, Dengliang; Zhang, Yilin; Xia, Lunguo; Xu, Ling; Kaplan, David L.; Jiang, Xinquan; Zhang, Fuqiang

2012-01-01

242

Effect of Different rhBMP-2 and TG-VEGF Ratios on the Formation of Heterotopic Bone and Neovessels  

PubMed Central

Bioengineered bone substitutes might represent alternatives to autologous bone grafts in medically compromised patients due to reduced operation time and comorbidity. Due to the lack of an inherent vascular system their dimension is limited to the size of critical bone size defect. To overcome this shortcoming, the experiment tried to create heterotopic bone around vessels. In vivo, a two-component fibrin and thrombin gel containing recombinant bone morphogenic protein (rhBMP-2) and transglutamate vascular endothelial growth factor (TG-VEGF) in different ratios, respectively, was injected into a dimensionally stable membrane tube, wrapped around the femoral vessel bundle in twelve New Zealand white rabbits. Sacrifice occurred eight weeks postoperatively. Microcomputed tomography of the specimens showed significantly increased bone volume in the rhBMP-2 to TG-VEGF ratio of 10 to 1 group. Histology showed new bone formation in close proximity to the vessel bundle. Immunohistochemistry detected increased angiogenesis within the newly formed bone in the rhBMP-2 to TG-VEGF ratios of 3 to 1 and 5 to 1. Heterotopic bone was engineered in vivo around vessels using different rhBMP-2 and TG-VEGF ratios in a fibrin matrix injected into a dimensionally stable membrane tube which prevented direct contact with skeletal muscles. PMID:24783213

Cai, Wei Xin; Li, Chun Lei; Ehrbar, Martin; Weber, Franz E.; Zwahlen, Roger A.

2014-01-01

243

Effect of different rhBMP-2 and TG-VEGF ratios on the formation of heterotopic bone and neovessels.  

PubMed

Bioengineered bone substitutes might represent alternatives to autologous bone grafts in medically compromised patients due to reduced operation time and comorbidity. Due to the lack of an inherent vascular system their dimension is limited to the size of critical bone size defect. To overcome this shortcoming, the experiment tried to create heterotopic bone around vessels. In vivo, a two-component fibrin and thrombin gel containing recombinant bone morphogenic protein (rhBMP-2) and transglutamate vascular endothelial growth factor (TG-VEGF) in different ratios, respectively, was injected into a dimensionally stable membrane tube, wrapped around the femoral vessel bundle in twelve New Zealand white rabbits. Sacrifice occurred eight weeks postoperatively. Microcomputed tomography of the specimens showed significantly increased bone volume in the rhBMP-2 to TG-VEGF ratio of 10 to 1 group. Histology showed new bone formation in close proximity to the vessel bundle. Immunohistochemistry detected increased angiogenesis within the newly formed bone in the rhBMP-2 to TG-VEGF ratios of 3 to 1 and 5 to 1. Heterotopic bone was engineered in vivo around vessels using different rhBMP-2 and TG-VEGF ratios in a fibrin matrix injected into a dimensionally stable membrane tube which prevented direct contact with skeletal muscles. PMID:24783213

Cai, Wei Xin; Zheng, Li Wu; Li, Chun Lei; Ma, Li; Ehrbar, Martin; Weber, Franz E; Zwahlen, Roger A

2014-01-01

244

A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept.  

PubMed

In an effort to produce clinically relevant volumes of tissue-engineered bone products, we report a direct perfusion bioreactor system. Goat bone marrow stromal cells (GBMSCs) were dynamically seeded and proliferated in this system in relevant volumes (10 cc) of small sized macroporous biphasic calcium phosphate scaffolds (BCP, 2-6 mm). Cell load and cell distribution were shown using methylene blue block staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining was used to demonstrate viability of the present cells. After 19 days of cultivation, the scaffolds were covered with a viable, homogeneous cell layer. The hybrid structures became interconnected and a dense layer of extracellular matrix was present as visualized by environmental scanning electron microscopy (ESEM). ESEM images showed within the extracellular matrix sphere like structures which were identified as calcium phosphate nodules by energy dispersive X-ray analysis (EDX). On line oxygen measurements during cultivation were correlated with proliferating GBMSCs. It was shown that the oxygen consumption can be used to estimate GBMSC population doubling times during growth in this bioreactor system. Implantation of hybrid constructs, which were proliferated dynamically, showed bone formation in nude mice after 6 weeks of implantation. On the basis of our results we conclude that a direct perfusion bioreactor system is capable of producing clinically relevant volumes of tissue-engineered bone in a bioreactor system which can be monitored on line during cultivation and show bone formation after implantation in nude mice. PMID:16125223

Janssen, Frank W; Oostra, Jaap; Oorschot, Arie van; van Blitterswijk, Clemens A

2006-01-01

245

Interaction between nandrolone decanoate and calcitonin in bone formation markers (osteocalcin and bone specific alkaline phosphatase) and IGF-I in rats.  

PubMed

Bone tissue has been shown to contain numerous cell-to-cell signaling peptides called growth factors. These growth factors are thought to have important regulating effects for bone remodeling, due to their potent effects on bone cell metabolism. Our investigation was intended to assess the effect of nandrolone decanoate and calcitonin treatment on biochemical markers of bone formation (bone alkaline phosphatase - osteocalcin) and insulin-like growth factor-I in rats. We studied 48 adult male rats. The animals were divided into four groups. Group (A) served as control. Animals in Group (B) were injected with 4 mg/kg/day nandrolone decanoate. Animals in Group (C) were injected with 400mU/rat/day calcitonin and Group (D) received combined therapy for seven days. Nandrolone decanoate and calcitonin have a mild but significant effect on insulin-like growth factor-I without affecting osteocalcin levels, while calcitonin alone decreases the BALP levels. The coadministration of two agents caused notable elevation on insulin-like growth factor-I, followed by a significant increase of osteocalcin and bone alkaline phosphatase. PMID:15758466

Saranteas, T; Mourouzis, C; Mezitis, M; Tesseromatis, C; Spyraki, C

2001-12-01

246

Hypoxia Modulates the Phenotype of Osteoblasts Isolated From Knee Osteoarthritis Patients, Leading to Undermineralized Bone Nodule Formation  

PubMed Central

Objective To investigate the role of hypoxia in the pathology of osteoarthritic (OA) bone by exploring its effect on the phenotype of isolated primary osteoblasts from patients with knee OA. Methods OA bone samples were collected at the time of elective joint replacement surgery for knee or hip OA. Normal bone samples were collected postmortem from cadaver donors. Primary osteoblasts were isolated from knee OA bone chips and cultured under normoxic or hypoxic (2% O2) conditions. Alkaline phosphatase activity was quantified using an enzymatic assay, and osteopontin and prostaglandin E2 (PGE2) production was assayed by enzyme-linked immunosorbent assay. Total RNA was extracted from bone and osteoblasts, and gene expression was profiled by quantitative reverse transcription–polymerase chain reaction. Results Human OA bone tissue sections stained positively for carbonic anhydrase IX, a biomarker of hypoxia, and exhibited differential expression of genes that mediate the vasculature and blood coagulation as compared to those found in normal bone. Culture of primary osteoblasts isolated from knee OA bone under hypoxic conditions profoundly affected the osteoblast phenotype, including the expression of genes that mediate bone matrix, bone remodeling, and bone vasculature. Hypoxia also increased the expression of cyclooxygenase 2 and the production of PGE2 by OA osteoblasts. Osteoblast expression of type II collagen ?1 chain, angiopoietin-like 4, and insulin-like growth factor binding protein 1 was shown to be mediated by hypoxia-inducible factor 1?. Chronic hypoxia reduced osteoblast- mineralized bone nodule formation. Conclusion These findings demonstrate that hypoxia can induce pathologic changes in osteoblast functionality consistent with an OA phenotype, providing evidence that hypoxia is a key driver of OA pathology. PMID:24574272

Chang, Joan; Jackson, Sonya G; Wardale, John; Jones, Simon W

2014-01-01

247

Fatigue of bi-lamellar microstructures  

SciTech Connect

The mechanical properties of Ti-castings with typically coarse lamellar microstructures can be improved by a heat treatment in the {alpha}+{beta}-phase field; during the subsequent cooling, fine {alpha} platelets can be precipitated in the {beta} phase which reduces the slip length effectively. This so-called bi-lamellar modification improves simultaneously the yield stress, the creep resistance and the fatigue strength; the latter, however, not to the full potential with respect to the increase in yield stress. For certain combinations of annealing temperature and cooling rate, the high-cycle fatigue strength of the bi-lamellar condition can be even lower than that of the lamellar condition despite a higher yield stress. The reason was found to be a narrow depleted zone in the {alpha} phase next to the {alpha}/{beta} interface. This soft layer can be healed by an additional heat treatment restoring the equilibrium concentration in the vicinity of the interface.

Schroeder, G.; Albrecht, J.; Luetjering, G.; Koike, J.; Folkers, K.D.; Liesner, Ch.

1999-07-01

248

Relative bone mass decreased in mice fed high dietary fat despite an increase in body mass and bone formation markers  

Technology Transfer Automated Retrieval System (TEKTRAN)

Osteoporosis and obesity are interrelated health disorders. Osteoblasts and adipocytes are derived from common mesenchymal stem cells and age-related osteoporosis is associated with increased bone marrow adipogenesis. To determine whether bone mass and osteoblast number and activity are affected by ...

249

Lamellar Self-Assembly Nanostructured Magnetic Materials  

Microsoft Academic Search

Synthesis of lamellar self-assemblies symmetric polystyrene–polybutylmethacrylate (PS–PBMA) copolymers, doped by magnetic nanoparticles was described. Self-assembly is a spontaneous process by which molecules and nanophase entities may materialize into organized aggregates or networks. As soon as particles are coated by a grafted PS layer, they can be confined in the PS layer of the polymeric smectic. The lamellar order was maintained

B. Hamdoun

2004-01-01

250

Heat and Radiofrequency Plasma Glow Discharge Pretreatment of a Titanium Alloy Promote Bone Formation and Osseointegration  

PubMed Central

Orthopedic and dental implants manifest increased failure rates when inserted into low density bone. We determined whether chemical pretreatments of a titanium alloy implant material stimulated new bone formation to increase osseointegration in vivo in trabecular bone using a rat model. Titanium alloy rods were untreated or pretreated with heat (600°C) or radiofrequency plasma glow discharge (RFGD). The rods were then coated with the extracellular matrix protein fibronectin (1 nM) or left uncoated and surgically implanted into the rat femoral medullary cavity. Animals were euthanized 3 or 6 weeks later, and femurs were removed for analysis. The number of trabeculae in contact with the implant surface, surface contact between trabeculae and the implant, and the length and area of bone attached to the implant were measured by histomorphometry. Implant shear strength was measured by a pull-out test. Both pretreatments and fibronectin enhanced the number of trabeculae bonding with the implant and trabeculae-to-implant surface contact, with greater effects of fibronectin observed with pretreated compared to untreated implants. RFGD pretreatment modestly increased implant shear strength, which was highly correlated (r2 = 0.87 – 0.99) with measures of trabecular bonding for untreated and RFGD-pretreated implants. In contrast, heat pretreatment increased shear strength 3 to 5-fold for both uncoated and fibronectin-coated implants at 3 and 6 weeks, suggesting a more rapid increase in implant-femur bonding compared to the other groups. In summary, our findings suggest that the heat and RFGD pretreatments can promote the osseointegration of a titanium alloy implant material. PMID:23649564

MacDonald, Daniel E.; Rapuano, Bruce E.; Vyas, Parth; Lane, Joseph M.; Meyers, Kathleen; Wright, Timothy

2013-01-01

251

Heat and radiofrequency plasma glow discharge pretreatment of a titanium alloy promote bone formation and osseointegration.  

PubMed

Orthopedic and dental implants manifest increased failure rates when inserted into low density bone. We determined whether chemical pretreatments of a titanium alloy implant material stimulated new bone formation to increase osseointegration in vivo in trabecular bone using a rat model. Titanium alloy rods were untreated or pretreated with heat (600°C) or radiofrequency plasma glow discharge (RFGD). The rods were then coated with the extracellular matrix protein fibronectin (1 nM) or left uncoated and surgically implanted into the rat femoral medullary cavity. Animals were euthanized 3 or 6 weeks later, and femurs were removed for analysis. The number of trabeculae in contact with the implant surface, surface contact between trabeculae and the implant, and the length and area of bone attached to the implant were measured by histomorphometry. Implant shear strength was measured by a pull-out test. Both pretreatments and fibronectin enhanced the number of trabeculae bonding with the implant and trabeculae-to-implant surface contact, with greater effects of fibronectin observed with pretreated compared to untreated implants. RFGD pretreatment modestly increased implant shear strength, which was highly correlated (r(2) = 0.87-0.99) with measures of trabecular bonding for untreated and RFGD-pretreated implants. In contrast, heat pretreatment increased shear strength 3-5-fold for both uncoated and fibronectin-coated implants at 3 and 6 weeks, suggesting a more rapid increase in implant-femur bonding compared to the other groups. In summary, our findings suggest that the heat and RFGD pretreatments can promote the osseointegration of a titanium alloy implant material. PMID:23649564

MacDonald, Daniel E; Rapuano, Bruce E; Vyas, Parth; Lane, Joseph M; Meyers, Kathleen; Wright, Timothy

2013-10-01

252

Epigenetic regulation of Tbx18 gene expression during endochondral bone formation.  

PubMed

Endochondral bone formation is tightly regulated by the spatial and sequential expression of a series of transcription factors. To disclose the roles of TBX18, a member of the T-box transcription factor family, during endochondral bone formation, its spatial and temporal expression patterns were characterized in the limb skeletal region of the developing mouse together with those of established osteochondrogenic markers Sox9, Col2a1, and Runx2. TBX18 expression first appeared in condensed mesenchymal cells (chondro-progenitors) in embryonic-day-10.5 (E10.5) limb bud and was co-localized with Sox9 expression, whereas at E11.5 and E12.5, it became undetectable in mesenchymal cells committed to the chondrocyte lineage. From E13.5 to E18.5, TBX18 expression reappeared in chondrocytes, correlating strongly with Col2a1 expression; furthermore, low level TBX18 expression was found in the Runx2-positive perichondral osteoblastic cell lineage. At the postnatal stage, TBX18 expression was observed in epiphyseal chondrocytes and osteocytes within the lacunae of mature trabecular bone. On the assumption that such characteristic Tbx18 gene expression is epigenetically regulated during mouse limb development, we examined the methylation status of the CpG-island in the mouse Tbx18 gene by methylation-specific polymerase chain reaction. Hypermethylation of the Tbx18 gene promoter became evident at an early embryonic stage in TBX18-negative cells and then disappeared at a late embryonic stage in TBX18-positive cells. Therefore, the temporal suppression of Tbx18 gene expression by the hypermethylation of its promoter seems to trigger the differentiation of mesenchymal cells into hypertrophic chondrocytes in the early stages of endochondral ossification. PMID:25380565

Haraguchi, Ryuma; Kitazawa, Riko; Kitazawa, Sohei

2014-11-01

253

The optimum zinc content in set calcium phosphate cement for promoting bone formation in vivo  

PubMed Central

The final aim of our study is to develop a novel calcium phosphate cement based on zinc-containing ?-tricalcium phosphate (?ZnTCP) and evaluate its potential as bonegraft material in vivo. In the present study, in vivo efficacy of zinc in hardened bodies of ?ZnTCP was explored. The hardened bodies prepared from ?ZnTCP with zinc content of 0.00, 0.04, 0.08, 0.11 and 0.19 wt % were prepared by mixing pure ?TCP or ?ZnTCP powder with 12 wt% sodium succinate solution at a solid-to-liquid ratio of 2.0. Due to the release of zinc ions into the physiological salt solution during curing, the zinc content in the hardened bodies was calculated to be 0.00, 0.03, 0.06, 0.10 and 0.18 wt%, respectively. The hardened bodies were implanted in the femora and tibia of white rabbits for 4 weeks. Histological and histomorphometric evaluation showed that the hardened body containing 0.03 wt% zinc, significantly promoted more new bone formation without evoking adverse tissue reactions than that without zinc. The hardened bodies containing 0.06 and 0.10 wt% zinc also resulted in the increase in numbers of active osteoblasts surrounding the new bone but caused inflammation at the implant sites. Results of this study indicate that the hardened body prepared with ?ZnTCP is superior to that prepared with ?TCP in promoting new bone formation due to the release of zinc ions. This study also indicates that the optimum amount of zinc in the hardened body is about 0.03 wt % to avoid inflammatory reaction. PMID:21461346

Li, Xia; Sogo, Yu; Ito, Atsuo; Mutsuzaki, Hirotaka; Ochiai, Naoyuki; Kobayashi, Takayuki; Nakamura, Satoshi; Yamashita, Kimihiro; LeGeros, Racquel Z.

2009-01-01

254

The p38? MAPK Function in Osteoprecursors Is Required for Bone Formation and Bone Homeostasis in Adult Mice  

PubMed Central

Background p38 MAPK activity plays an important role in several steps of the osteoblast lineage progression through activation of osteoblast-specific transcription factors and it is also essential for the acquisition of the osteoblast phenotype in early development. Although reports indicate p38 signalling plays a role in early skeletal development, its specific contributions to adult bone remodelling are still to be clarified. Methodology/Principal Findings We evaluated osteoblast-specific deletion of p38? to determine its significance in early skeletogenesis, as well as for bone homeostasis in adult skeleton. Early p38? deletion resulted in defective intramembranous and endochondral ossification in both calvaria and long bones. Mutant mice showed reduction of trabecular bone volume in distal femurs, associated with low trabecular thickness. In addition, knockout mice also displayed decreased femoral cortical bone volume and thickness. Deletion of p38? did not affect osteoclast function. Yet it impaired osteoblastogenesis and osteoblast maturation and activity through decreased expression of osteoblast-specific transcription factors and their targets. Furthermore, the inducible Cre system allowed us to control the onset of p38? disruption after birth by removal of doxycycline. Deletion of p38? at three or eight weeks postnatally led to significantly lower trabecular and cortical bone volume after 6 or 12 months. Conclusions Our data demonstrates that, in addition to early skeletogenesis, p38? is essential for osteoblasts to maintain their function in mineralized adult bone, as bone anabolism should be sustained throughout life. Moreover, our data also emphasizes that clinical development of p38 inhibitors should take into account their potential bone effects. PMID:25007355

Rodríguez-Carballo, Edgardo; Gámez, Beatriz; Sedó-Cabezón, Lara; Sánchez-Feutrie, Manuela; Zorzano, Antonio; Manzanares-Céspedes, Cristina; Rosa, José Luis; Ventura, Francesc

2014-01-01

255

Evaluation of bone formation guided by DNA/protamine complex with FGF-2 in an adult rat calvarial defect model.  

PubMed

DNA/protamine complex paste (D/P) and D/P complex paste with Fibroblast Growth Factor-2 (FGF-2) (D/P-FGF) were prepared to investigate their new bone formation abilities using an ?40-week-old rat calvarial defect model. It was found that D/P could release FGF-2 proportionally in an in vitro experiment with an enzyme-linked immunosorbent assay. It was also found that aging adversely affected self-bone healing of rats by comparison with the results in a previous study using 10-week-old rats. Microcomputed tomography and histopathological examinations showed that new bone formation abilities of D/P and D/P-FGF were superior to that of the control (sham operation). Control, D/P and D/P-FGF showed newly formed bone areas of 6.7, 58.3, and 67.0%, respectively, 3 months after the operation. Moreover, it was found that FGF-2 could support the osteoanagenesis ability of D/P. It was considered that FGF-2 could play an important role in new bone formation at early stages because it induced the genes such as collagen I, CBFA, OSX, and OPN, which are initiated first in the process of osteogenesis. Therefore, D/P-FGF will be a useful injectable biomaterial with biodegradable properties for the repair of bone defects in the elderly. PMID:24664968

Shinozaki, Yosuke; Toda, Masako; Ohno, Jun; Kawaguchi, Minoru; Kido, Hirofumi; Fukushima, Tadao

2014-11-01

256

Bone morphogenetic proteins, eye patterning, and retinocollicular map formation in the mouse  

PubMed Central

Patterning events during early eye formation determine retinal cell fate and can dictate the behavior of retinal ganglion cell (RGC) axons as they navigate toward central brain targets. The temporally and spatially regulated expression of bone morphogenetic proteins (BMPs) and their receptors in the retina are thought to play a key role in this process, initiating gene expression cascades that distinguish different regions of the retina, particularly along the dorsoventral axis. Here, we examine the role of BMP and a potential downstream effector, EphB, in retinotopic map formation in the lateral geniculate nucleus (LGN) and superior colliculus (SC). RGC axon behaviors during retinotopic map formation in wild type mice are compared with those in several strains of mice with engineered defects of BMP and EphB signaling. Normal RGC axon sorting produces axon order in the optic tract that reflects the dorsoventral position of the parent RGCs in the eye. A dramatic consequence of disrupting BMP signaling is a missorting of RGC axons as they exit the optic chiasm. This sorting is not dependent on EphB. When BMP signaling in the developing eye is genetically modified, RGC order in the optic tract and targeting in the LGN and SC are correspondingly disrupted. These experiments show that BMP signaling regulates dorsoventral RGC cell fate, RGC axon behavior in the ascending optic tract and retinotopic map formation in the LGN and SC through mechanisms that are in part distinct from EphB signaling in the LGN and SC. PMID:18614674

Plas, Daniel T.; Dhande, Onkar; Lopez, Joshua E.; Murali, Deepa; Thaller, Christina; Henkemeyer, Mark; Furuta, Yasuhide; Overbeek, Paul; Crair, Michael C.

2009-01-01

257

Bone formation rather than inflammation reflects Ankylosing Spondylitis activity on PET-CT: a pilot study  

PubMed Central

Introduction Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [18F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference. Methods In a stepwise approach different PET tracers were investigated. First, whole body [18F]FDG and [11C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [18F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data. Results No increased [18F]FDG and [11C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [18F]Fluoride PET-CT, [18F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [18F]FDG depicted only three lesions, with an uptake of five times lower compared to [18F]Fluoride, and again no [11C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [18F]Fluoride uptake. Conventional radiographs showed structural bony changes in 11 out of 17 [18F]Fluoride PET positive lesions. Conclusions Our PET-CT data suggest that AS activity is reflected by bone activity (formation) rather than inflammation. The results also show the potential value of PET-CT for imaging AS activity using the bone tracer [18F]Fluoride. In contrast to active RA, inflammation tracers [18F]FDG and [11C](R)PK11195 appeared to be less useful for AS imaging. PMID:22471910

2012-01-01

258

Optimisation of the differing conditions required for bone formation in vitro by primary osteoblasts from mice and rats  

PubMed Central

The in vitro culture of calvarial osteoblasts from neonatal rodents remains an important method for studying the regulation of bone formation. The widespread use of transgenic mice has created a particular need for a reliable, simple method that allows the differentiation and bone-forming activity of murine osteoblasts to be studied. In the present study, we established such a method and identified key differences in optimal culture conditions between mouse and rat osteoblasts. Cells isolated from neonatal rodent calvariae by collagenase digestion were cultured for 14–28 days before staining for tissue non-specific alkaline phosphatase (TNAP) and bone mineralisation (alizarin red). The reliable differentiation of mouse osteoblasts, resulting in abundant TNAP expression and the formation of mineralised ‘trabecular-shaped’ bone nodules, occurred only following culture in ? minimum essential medium (?MEM) and took 21–28 days. Dexamethasone (10 nM) inhibited bone mineralisation in the mouse osteoblasts. By contrast, TNAP expression and bone formation by rat osteoblasts were observed following culture in both ?MEM and Dulbecco’s modified Eagle’s medium (DMEM) after approximately 14 days (although ~3-fold more effectively in ?MEM) and was strongly dependent on dexamethasone. Both the mouse and rat osteoblasts required ascorbate (50 ?g/ml) for osteogenic differentiation and ?-glycerophosphate (2 mM) for mineralisation. The rat and mouse osteoblasts showed similar sensitivity to the well-established inhibitors of mineralisation, inorganic pyrophosphate (PPi) and adenosine triphosphate (ATP; 1–100 ?M). The high efficiency of osteogenic differentiation observed following culture in ?MEM, compared with culture in DMEM possibly reflects the richer formulation of the former. These findings offer a reliable technique for inducing mouse osteoblasts to form bone in vitro and a more effective method for culturing bone-forming rat osteoblasts. PMID:25200658

ORRISS, ISABEL R.; HAJJAWI, MARK O.R.; HUESA, CARMEN; MACRAE, VICKY E.; ARNETT, TIMOTHY R.

2014-01-01

259

Bio-activated titanium surface utilizable for mimetic bone implantation in dentistry—Part III: Surface characteristics and bone implant contact formation  

NASA Astrophysics Data System (ADS)

This study was carried out to quantify the effect of an alkali-modified surface on the bone implant interface formation during healing using an animal model. A total of 24 screw-shaped, self-tapping, (c.p.) titanium dental implants, divided into test group B—implants with alkali-modified surface (Bio surface) and control group M—implants with turned, machined surface, were inserted without pre-tapping in the tibiae of three beagle dogs. The animals were sacrificed after 2, 5 and 12 weeks and the bone implant contact (BIC%) was evaluated histometrically. The surface characteristics that differed between the implant surfaces, i.e. specific surface area, contact angle, may represent factors that influence the rate of osseointegration and the secondary implant stability. The alkali-treated surface enhances the BIC formation during the first 2 5 weeks of healing compared to the turned, machined surface.

Strnad, Jakub; Strnad, Zden?k; Šesták, Jaroslav; Urban, Karel; Povýšil, Ctibor

2007-05-01

260

Evidence for estrogen receptor expression during medullary bone formation and resorption in estrogen-treated male Japanese quails (Coturnix coturnix japonica).  

PubMed

The temporal expression of estrogen receptor (ER)-? and ER-? mRNA was examined in male Japanese quails. Femurs of quails receiving 17?-estradiol underwent RT-PCR and histochemical analysis 1 to 15 days after treatment. Untreated quails were used as controls (day 0). Between days 0 and 5, cells lining the bone endosteal surface differentiated into osteoblasts, which in turn formed medullary bone. Expression of ER-? was already observed on day 0 and increased slightly during bone formation whereas ER-? was hardly detected throughout this process. After osteoclasts appeared on the medullary bone surface, this type of bone disappeared from the bone marrow cavity (days 7˜15). ER-? expression simultaneously decreased slightly and ER-? levels remained very low. These results suggest that estrogen activity mediated by ER-? not only affects medullary bone formation but also bone resorption. PMID:23000578

Hiyama, Shinji; Sugiyama, Toshie; Kusuhara, Seiji; Uchida, Takashi

2012-09-01

261

Evidence for estrogen receptor expression during medullary bone formation and resorption in estrogen-treated male Japanese quails (Coturnix coturnix japonica)  

PubMed Central

The temporal expression of estrogen receptor (ER)-? and ER-? mRNA was examined in male Japanese quails. Femurs of quails receiving 17?-estradiol underwent RTPCR and histochemical analysis 1 to 15 days after treatment. Untreated quails were used as controls (day 0). Between days 0 and 5, cells lining the bone endosteal surface differentiated into osteoblasts, which in turn formed medullary bone. Expression of ER-? was already observed on day 0 and increased slightly during bone formation whereas ER-? was hardly detected throughout this process. After osteoclasts appeared on the medullary bone surface, this type of bone disappeared from the bone marrow cavity (days 7~15). ER-? expression simultaneously decreased slightly and ER-? levels remained very low. These results suggest that estrogen activity mediated by ER-? not only affects medullary bone formation but also bone resorption. PMID:23000578

Sugiyama, Toshie; Kusuhara, Seiji; Uchida, Takashi

2012-01-01

262

Evaluation of circulating levels of inflammatory and bone formation markers in axial spondyloarthritis.  

PubMed

Studies have demonstrated the important role of bone remodelling and osteoimmunology in the progression of inflammatory lesions in axial spondyloarthritis (SpA) disease. This study was conducted to evaluate the inflammatory response by analysis of the serum levels of pro-inflammatory and new bone formation markers in patients with axial SpA who were treated or not treated with anti-tumour necrosis factor-? (anti-TNF-?) or non-steroidal drugs (NSAIDs) and to identify whether these drugs modify the activity and severity of the disease. The serum levels of myeloperoxidase (MPO), adenosine deaminase (ADA), nitric oxide metabolites (NOx), bone alkaline phosphatase (BAP), Dickkopf-1 (DKK-1), and osteoprotegerin (OP) were measured in 52 SpA patients who were treated or not with anti-TNF-? or NSAIDs and in 26 healthy controls using colourimetric and enzyme immunoassay tests. The activity and the severity of illness in patients with SpA were assessed using questionnaires (Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)). A significant difference between the controls and the patients without medication was observed in relation to NOx, BAP, and OP (p<0.01). When the patients were compared with regard to their treatment, there were no clinically significant differences between the groups (p>0.05). In conclusion, The NOx, BAP, and OP are emerging as important inflammatory pathways in axial SpA. Also the anti-TNF-? or non-steroidal drugs reduce the inflammation and destructions, however these treatments do not modify the serum levels of these biomarkers. PMID:24925756

de Andrade, Kenia Rodrigues; de Castro, Gláucio Ricardo Werner; Vicente, Geison; da Rosa, Julia Salvan; Nader, Marina; Pereira, Ivanio Alves; Fröde, Tânia Silvia

2014-08-01

263

Staphylococcal biofilm formation on the surface of three different calcium phosphate bone grafts: a qualitative and quantitative in vivo analysis.  

PubMed

Differences in physico-chemical characteristics of bone grafts to fill bone defects have been demonstrated to influence in vitro bacterial biofilm formation. Aim of the study was to investigate in vivo staphylococcal biofilm formation on different calcium phosphate bone substitutes. A foreign-body guinea-pig infection model was used. Teflon cages prefilled with ?-tricalcium phosphate, calcium-deficient hydroxyapatite, or dicalcium phosphate (DCP) scaffold were implanted subcutaneously. Scaffolds were infected with 2 × 10(3) colony-forming unit of Staphylococcus aureus (two strains) or S. epidermidis and explanted after 3, 24 or 72 h of biofilm formation. Quantitative and qualitative biofilm analysis was performed by sonication followed by viable counts, and microcalorimetry, respectively. Independently of the material, S. aureus formed increasing amounts of biofilm on the surface of all scaffolds over time as determined by both methods. For S. epidermidis, the biofilm amount decreased over time, and no biofilm was detected by microcalorimetry on the DCP scaffolds after 72 h of infection. However, when using a higher S. epidermidis inoculum, increasing amounts of biofilm were formed on all scaffolds as determined by microcalorimetry. No significant variation in staphylococcal in vivo biofilm formation was observed between the different materials tested. This study highlights the importance of in vivo studies, in addition to in vitro studies, when investigating biofilm formation of bone grafts. PMID:25693675

Furustrand Tafin, Ulrika; Betrisey, Bertrand; Bohner, Marc; Ilchmann, Thomas; Trampuz, Andrej; Clauss, Martin

2015-03-01

264

Diabetes interferes with the bone formation by affecting the expression of transcription factors that regulate osteoblast differentiation.  

PubMed

Type 1 diabetes in humans has as one of its complications inadequate bone formation, resulting in osteopenia and delayed fracture healing. To investigate the mechanisms by which diabetes affects bone formation, experiments were performed in a marrow ablation model. Mice were made diabetic by multiple low-dose streptozotocin treatment, and controls were treated with vehicle alone. Killing occurred 0, 2, 4, 6, 10, and 16 d following marrow ablation. Histologic analysis demonstrated that the amount of immature mesenchymal tissue was equivalent in both the experimental and control groups on d 4. On d 6 a burst of bone formation occurred in the control group that was significantly reduced in the diabetic group. This deficit was evident at the molecular level as shown by diminished expression of osteocalcin, collagen types I. When transcription factors were examined, core-binding factor alpha1 (Cbfa1)/runt domain factor-2 (Runx-2) and human homolog of the drosophila distal-less gene (Dlx5) expression were substantially reduced in the diabetic, compared with control, groups on d 4 and 6. C-fos but not c-jun expression was also suppressed in the diabetic group but not closely linked to bone formation. Insulin treatment substantially reversed the effect of diabetes on the expression of bone matrix osteocalcin and collagen type I and transcription factors Cbfa1/Runx2 and Dlx5. These results indicate that diabetic animals produce sufficient amounts of immature mesenchymal tissue but fail to adequately express genes that regulate osteoblast differentiation, Cbfa1/Runx-2 and Dlx5, which in turn, leads to decreased bone formation. PMID:12488363

Lu, Huafei; Kraut, Douglas; Gerstenfeld, Louis C; Graves, Dana T

2003-01-01

265

Growth hormone and mild exercise in combination markedly enhance cortical bone formation and strength in old rats.  

PubMed

The effects of a combination of mild exercise and GH injections on bone were studied in old female rats. Biosynthetic human GH, 2.7 mg/kg/day, was injected s.c. for 73 days. Exercised rats ran 8 m/min on a treadmill for 1 h/day. All rats (age 21 months old) were labeled with a tetracycline injection 56 days and a calcein injection 11 days before killing. The GH injections resulted in an 11-fold increase in femoral middiaphyseal bone formation rate and a 12% increase in cross-sectional area compared with the saline-injected group. The mild exercise doubled the mineralizing surface but did not influence the bone formation rate significantly. The combination of GH injections plus exercise, however, resulted in a further increase of 39% in bone formation rate, primarily at the anterolateral aspects, and an increase of 5% in cross-sectional area compared with the group injected with GH only. The femur ultimate breaking load was increased by 37% and the stiffness by 42% in the group injected with GH compared with the saline-injected group. Exercise alone did not influence the femur mechanical properties. The combination of GH injections plus exercise induced a 4% further increase in ultimate breaking load and 7% further increase in stiffness compared with the group injected with GH alone. The GH injections induced a 117% increase in serum insulin-like growth factor I. The GH-insulin-like growth factor I axis stimulates recruitment of osteoblast precursor cells, resulting in increased bone formation at the periosteal surface. GH injections and mild excercise in combination modulate and increase further the formation and strength of cortical bone in old female rats. PMID:9528976

Oxlund, H; Andersen, N B; Ortoft, G; Orskov, H; Andreassen, T T

1998-04-01

266

Spectroscopic investigation on formation and growth of mineralized nanohydroxyapatite for bone tissue engineering applications.  

PubMed

Synthetic calcium hydroxyapatite (HAP,Ca(10)(PO(4))(6)(OH)(2)) is a well-known bioceramic material used in orthopaedic and dental applications because of its excellent biocompatibility and bone-bonding ability. Substitution of trace elements, such as Sr, Mg and Zn ions into the structure of calcium phosphates is the subject of widespread investigation. In this paper, we have reported the synthesis of Sr, Mg and Zn co-substituted nanohydroxyapatite by soft solution freezing method. The effect of pH on the morphology of bioceramic nanomaterial was also discussed. The in vitro bioactivity of the as-synthesized bioceramic nanomaterial was determined by soaking it in SBF for various days. The as-synthesized bioceramic nanomaterial was characterized by Fourier transform infrared spectroscopy, X- ray diffraction analysis, Scanning electron microscopy and Energy dispersive X-ray analysis and Transmission electron microscopic techniques respectively. The results obtained in our study have revealed that pH 10 was identified to induce the formation of mineralized nanohydroxyapatite. It is observed that the synthesis of bioceramic nanomaterial not only support the growth of apatite layer on its surface but also accelerate the growth which is evident from the in vitro studies. Therefore, mineralized nanohydroxyapatite is a potential candidate in bone tissue engineering. PMID:22446767

Gopi, D; Nithiya, S; Shinyjoy, E; Kavitha, L

2012-06-15

267

Spectroscopic investigation on formation and growth of mineralized nanohydroxyapatite for bone tissue engineering applications  

NASA Astrophysics Data System (ADS)

Synthetic calcium hydroxyapatite (HAP,Ca10(PO4)6(OH)2) is a well-known bioceramic material used in orthopaedic and dental applications because of its excellent biocompatibility and bone-bonding ability. Substitution of trace elements, such as Sr, Mg and Zn ions into the structure of calcium phosphates is the subject of widespread investigation. In this paper, we have reported the synthesis of Sr, Mg and Zn co-substituted nanohydroxyapatite by soft solution freezing method. The effect of pH on the morphology of bioceramic nanomaterial was also discussed. The in vitro bioactivity of the as-synthesized bioceramic nanomaterial was determined by soaking it in SBF for various days. The as-synthesized bioceramic nanomaterial was characterized by Fourier transform infrared spectroscopy, X- ray diffraction analysis, Scanning electron microscopy and Energy dispersive X-ray analysis and Transmission electron microscopic techniques respectively. The results obtained in our study have revealed that pH 10 was identified to induce the formation of mineralized nanohydroxyapatite. It is observed that the synthesis of bioceramic nanomaterial not only support the growth of apatite layer on its surface but also accelerate the growth which is evident from the in vitro studies. Therefore, mineralized nanohydroxyapatite is a potential candidate in bone tissue engineering.

Gopi, D.; Nithiya, S.; Shinyjoy, E.; Kavitha, L.

268

Anabolic Bone Formation Via a Site Specific Bone Targeting Delivery System by Interfering with Semaphorin 4D Expression.  

PubMed

Recently semaphorins have been targeted as new molecules directly implicated in the cell-cell communication that occurs between osteoclasts and osteoblasts. Over-expression of certain semaphorins such as semaphorin4D (sema4D) is found in an osteoporotic phenotype and plays a key role in osteoclast activity by suppressing osteoblast maturation, thus significantly altering the bone modelling cycle. In the present study, we fabricate a site-specific bone-targeting drug delivery system from polymeric nanoparticles with the incorporation of siRNA interference molecule for sema4D and demonstrate their cellular uptake and intracellular trafficking within osteoclasts, thus preventing the suppression of osteoblast activity. We then demonstrate in an osteoporotic animal model induced by ovariectomy that weekly intravenous injections led to a significantly greater number of active osteoblasts at the bone surface resulting in higher bone volume in compromised animals. The findings from the present study demonstrate a novel and promising site-specific therapeutic option for the treatment of osteoporosis via interference of the sema4D-plexin cell communication pathway between osteoclasts and osteoblasts. © 2014 American Society for Bone and Mineral Research. PMID:25088728

Zhang, Yufeng; Wei, Lingfei; Miron, Richard J; Shi, Bin; Bian, Zhuan

2014-08-01

269

Platelet lysate coating on scaffolds directly and indirectly enhances cell migration, improving bone and blood vessel formation.  

PubMed

Suitable colonization and vascularization of tissue-engineered constructs after transplantation represent critical steps for the success of bone repair. Human platelet lysate (hPL) is composed of numerous growth factors known for their proliferative, differentiative and chemo-attractant effects on various cells involved in wound healing and bone growth. The aim of this study was to determine whether the delivery of human mesenchymal stromal cells (hMSC) seeded on hPL-coated hydroxyapatite/?-tricalcium phosphate (HA/?-TCP) scaffolds could enhance vascularization and bone formation, as well as to investigate the mechanisms by which hMSC participate in tissue regeneration. Our study demonstrates that hPL can be coated on HA/?-TCP scaffolds, which play direct and indirect effects on implanted and/or resident stem cells. Effectively, we show that hPL coating directly increases chemo-attraction to and adhesion of hMSC and endothelial cells on the scaffold. Moreover, we show that hPL coating induces hMSC to produce and secrete pro-angiogenic proteins (placental growth factor and vascular endothelial growth factor) which allow the proliferation and specific chemo-attraction of endothelial cells in vitro, thus improving in vivo neovascularization and new bone formation. This study highlights the potential of functionalizing biomaterials with hPL and shows that this growth factor combination can have synergistic effects leading to enhanced bone and blood vessel formation. PMID:23403167

Leotot, Julie; Coquelin, Laura; Bodivit, Gwellaouen; Bierling, Philippe; Hernigou, Philippe; Rouard, Helene; Chevallier, Nathalie

2013-05-01

270

Inhibitory effects of osteoblasts and increased bone formation on myeloma in novel culture systems and a myelomatous mouse model  

PubMed Central

Background and Objectives Multiple myeloma (MM) growth in the bone marrow is associated with increased osteoclast activity and a reduced number of osteoblasts. Experimental studies suggest that bone disease drives the progression of MM. Whereas those studies focused on the critical role of myeloma-induced osteoclastogenesis in disease progression, little is known about the impact of osteoblasts and increased bone formation on MM. Design and Methods We investigated the effect of isolated osteoblasts and osteoclasts on survival and proliferation of primary MM plasma cells (PC) in co-cultures and triple-cultures, and tested the effect of mesenchymal stem cells (MSC) on bone mineral density and MM growth in myelomatous human bones of SCID-hu mice. Results Whereas osteoclasts promoted survival and proliferation of MM PC, osteoblasts supported or inhibited MM PC, depending on the source of the MM cells. In triple-cultures osteoblasts attenuated the effect of osteoclasts on MM PC in 18 of 24 experiments. The anti-MM response to osteoblasts correlated with advanced clinical stage. Injection of MSC into myelomatous bones resulted in marked inhibition of tumor growth in three of nine experiments and stabilization of disease in two additional experiments. The anti-MM response of MSC was associated with increased human bone mineral density. Immunohistochemical analysis indicated that the MSC were well engrafted and, in responding mice, differentiated into osteogenic cells. Interpretation and Conclusions MM PC from the majority of patients are susceptible to growth inhibition by osteoblasts; however, growth of MM PC from certain patients is accelerated by osteoblasts. In vivo, increased bone formation is associated with reduced myeloma burden. PMID:16461303

Yaccoby, Shmuel; Wezeman, Michele J.; Zangari, Maurizio; Walker, Ronald; Cottler-Fox, Michele; Gaddy, Danna; Ling, Wen; Saha, Rinku; Barlogie, Bart; Tricot, Guido; Epstein, Joshua

2006-01-01

271

MRI evaluation of tibial tunnel wall cortical bone formation after platelet-rich plasma applied during anterior cruciate ligament reconstruction  

PubMed Central

Background After anterior cruciate ligament (ACL) reconstruction, formation of cortical sclerotic bone encircling the femoral and tibial tunnel is a part of intratunnel graft healing. During the physiological cascades of soft tissue healing and bone growth, cellular and hormonal factors play an important role. The purpose of this study was to non-invasively but quantitatively assess the effect of intraoperatively applied platelet-rich plasma (PRP) on the formation of cortical bone encircling the tibial tunnel. Patients and methods In fifty patients, standard arthroscopic ACL reconstructions were performed. The PRP group (n = 25) received a local application of PRP while the control group (n = 25) did not receive PRP. The proximal tibial tunnel was examined by MRI in the paraxial plane where the portion of the tibial tunnel wall circumference consisting of sclerotic cortical bone was assessed with testing occurring at one, two and a half and six months after surgery. Results At one month after surgery, differences between the groups in the amount of cortical sclerotic bone encircling the tunnel were not significant (p = 0.928). At two and a half months, the sclerotic portion of the tunnel wall in the PRP group (36.2%) was significantly larger than in the control (22.5%) group (p = 0.004). At six months, the portion of sclerotic bone in the PRP group (67.1%) was also significantly larger than in the control (53.5%) group (p = 0.003). Conclusions Enhanced cortical bone formation encircling the tibial tunnel at 2.5 and 6 months after ACL graft reconstruction results from locally applied platelet-rich plasma. PMID:23801907

Rupreht, Mitja; Vogrin, Matjaž; Hussein, Mohsen

2013-01-01

272

Identification of enoxacin as an inhibitor of osteoclast formation and bone resorption by structure-based virtual screening.  

PubMed

An interaction between the B2 subunit of vacuolar H(+)-ATPase (V-ATPase) and microfilaments is required for osteoclast bone resorption. An atomic homology model of the actin binding site on B2 was generated and molecular docking simulations were performed. Enoxacin, a fluoroquinolone antibiotic, was identified and in vitro testing demonstrated that enoxacin blocked binding between purified B2 and microfilaments. Enoxacin dose dependently reduced the number of osteoclasts differentiating in mouse marrow cultures stimulated with 1,25-dihydroxyvitamin D(3), as well as markers of osteoclast activity, and the number of resorption lacunae formed on bone slices. Enoxacin inhibited osteoclast formation at concentrations where osteoblast formation was not altered. In summary, enoxacin is a novel small molecule inhibitor of osteoclast bone resorption that acts by an unique mechanism and is therefore an attractive lead molecule for the development of a new class of antiosteoclastic agents. PMID:19630402

Ostrov, David A; Magis, Andrew T; Wronski, Thomas J; Chan, Edward K L; Toro, Edgardo J; Donatelli, Richard E; Sajek, Kristen; Haroun, Ireni N; Nagib, Michael I; Piedrahita, Ana; Harris, Ashley; Holliday, L Shannon

2009-08-27

273

Long-Term Symptoms Onset and Heterotopic Bone Formation around a Total Temporomandibular Joint Prosthesis: a Case Report  

PubMed Central

ABSTRACT Background The literature on total alloplastic temporomandibular joint (TMJ) reconstructions is encouraging, and studies on total alloplastic TMJ replacements outcomes showed acceptable improvements in terms of both pain levels and jaw function. Nevertheless, some adverse events, such as heterotopic bone formation around the implanted prosthesis, may occur. In consideration of that, the present manuscript describes a case of heterotopic bone formation around a total temporomandibular joint prosthesis, which occurred several years after the implant. Methods The present manuscript describes a case of heterotopic bone formation around a total TMJ prosthesis, which occurred several years after the implant in patients, who previously underwent multiple failed TMJ surgeries. Results Ten years after the surgical TMJ replacement to solve an ankylotic bone block, the patient came to our attention again referring a progressive limitation in mouth opening. A computerized tomography showed evidence of marked heterotopic bone formation in the medial aspects of the joint, where a new-born ankylotic block occupied most part of the gap created by resecting the coronoid process at the time of the TMJ prosthesis insertion. Conclusions Despite this adverse event has been sometimes described in the literature, this is the first case in which its occurrence happened several years after the temporomandibular joint replacement. It can be suggested that an accurate assessment of pre-operative risk factors for re-ankylosis (e.g., patients with multiple failed temporomandibular joint surgeries) and within-intervention prevention (e.g., strategies to keep the bone interfaces around the implant separated) should be better standardized and define in future studies. PMID:24800055

Guarda-Nardini, Luca; Manfredini, Daniele; Ferronato, Giuseppe

2014-01-01

274

Bone marrow cells recruited through the neuropilin-1 receptor promote arterial formation at the sites of adult neoangiogenesis in mice  

PubMed Central

Experimental and clinical evidence indicate that bone marrow cells participate in the process of new blood vessel formation. However, the molecular mechanisms underlying their recruitment and their exact role are still elusive. Here, we show that bone marrow cells are recruited to the sites of neoangiogenesis through the neuropilin-1 (NP-1) receptor and that they are essential for the maturation of the activated endothelium and the formation of arteries in mice. By exploiting adeno-associated virus vector–mediated, long-term in vivo gene expression, we show that the 165-aa isoform of VEGF, which both activates the endothelium and recruits NP-1+ myeloid cells, is a powerful arteriogenic agent. In contrast, neither the shortest VEGF121 isoform, which does not bind NP-1 and thus does not recruit bone marrow cells, nor semaphorin 3A, which attracts cells but inhibits endothelial activation, are capable of sustaining arterial formation. Bone marrow myeloid cells are not arteriogenic per se nor are they directly incorporated in the newly formed vasculature, but they contribute to arterial formation through a paracrine effect ensuing in the activation and proliferation of tissue-resident smooth muscle cells. PMID:18483621

Zacchigna, Serena; Pattarini, Lucia; Zentilin, Lorena; Moimas, Silvia; Carrer, Alessandro; Sinigaglia, Milena; Arsic, Nikola; Tafuro, Sabrina; Sinagra, Gianfranco; Giacca, Mauro

2008-01-01

275

Expanding the scope of lamellar keratoplasty.  

PubMed Central

PURPOSE: To investigate whether applications of current technology, such as cryolathe and excimer laser, might improve outcomes and increase use of lamellar keratoplasty. METHODS: Six studies were performed, beginning with animals and progressing to human subjects. The first study compared cryolathed with hand-dissected rabbit corneas to ascertain which created a smoother donor interface. The second animal pilot study was done to determine whether thickness of donor cornea resection could be accurately predicted with the cryolathe. A prospective animal trial was then undertaken to compare lamellar keratoplasty outcomes using cryolathed versus hand-dissected tissue. The fourth work extrapolated previous animal findings to lamellar keratoplasty in human disease. Finally, two ongoing studies are described. The first explores the possibility of sutureless lamellar keratoplasty. The second utilizes the excimer laser to dissect the recipient stromal bed. RESULTS: The initial animal pilot study demonstrated a clearer stromal surface in cryolathed versus hand-dissected corneal tissue. The second pilot showed that plano-powered donor tissue could be generated to predetermined thickness. The prospective animal trial revealed that clear grafts of intended thickness could be obtained with cryolathing. Human studies suggested that lamellar keratoplasty using cryolathe-prepared donor tissue may offer superior results to free-hand dissection. Finally, one ongoing study indicates that sutureless lamellar keratoplasty is untenable, and the other shows that clear grafts can be obtained by combining cryolathed donor tissue with recipient photoablation. CONCLUSION: This body of work demonstrates that use of new lamellar keratoplasty technology may offer expanded scope and better outcomes than traditional lamellar keratoplasty techniques. Images FIGURE 1 FIGURE 3 FIGURE 4A FIGURE 4B FIGURE 8A FIGURE 8B FIGURE 9 FIGURE 10 FIGURE 10B FIGURE 11A FIGURE 11B FIGURE 12A FIGURE 12B FIGURE 13 FIGURE 14A FIGURE 14B FIGURE 15A FIGURE 15B FIGURE 15C FIGURE 16A FIGURE 16B FIGURE 18A FIGURE 18B FIGURE 19 FIGURE 20 FIGURE 21 PMID:10703145

Rich, L F

1999-01-01

276

Secreted Phosphoprotein 24 kD (Spp24) and Spp14 Affect TGF-? Induced Bone Formation Differently  

PubMed Central

Transforming growth factor-? (TGF-?) and bone morphogenetic proteins (BMPs) have opposing but complementary functions in directing bone growth, repair, and turnover. Both are found in the bone matrix. Proteins that bind to and affect the activity of these growth factors will determine the relative abundance of the growth factors and, therefore, regulate bone formation. Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that has been demonstrated to bind to and affect the activity of BMPs. The arginine-rich carboxy terminus of Spp24 is proteolytically processed to produce three other predictable truncation products (Spp18.1, Spp16.0, and Spp14.5). In this work, we report that kinetic data obtained by surface plasmon resonance demonstrate that Spp24 and the three C-terminal truncation products all bind to TGF-?1 and TGF-?2 with a similar but somewhat less affinity than they bind BMP-2; that, as in the case of BMP-2, the full-length (FL) form of Spp24 binds TGF-? with greater affinity than do the truncation products; that FL-Spp24 inhibits TGF-?2 induced bone formation in vivo, but Spp14.5 does not; and that co-administration of FL-Spp24 or Spp14.5 with TGF-?2 in vivo is associated with a reduction in the amount of cartilage, relative to new bone, present at the site of injection. This finding is consistent with the observation that low-dose TGF-? administration in vivo is associated with greater bone formation than high-dose TGF-? administration, and suggests that one function of Spp24 and its truncation products is to down-regulate local TGF-? activity or availability during bone growth and development. The similarities and differences of the interactions between Spp24 proteins and TGF-? compared to the interaction of the Spp24 proteins and BMPs have significant implications with respect to the regulation of bone metabolism and with respect to engineering therapeutic proteins for skeletal disorders. PMID:23991133

Tian, Haijun; Bi, Xiaoda; Li, Chen-Shuang; Zhao, Ke-Wei; Brochmann, Elsa J.; Montgomery, Scott R.; Aghdasi, Bayan; Chen, Deyu; Daubs, Michael D.; Wang, Jeffrey C.; Murray, Samuel S.

2013-01-01

277

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects  

PubMed Central

There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling. PMID:23941405

Dumas, Jerald E.; Prieto, Edna M.; Zienkiewicz, Katarzyna J.; Guda, Teja; Wenke, Joseph C.; Bible, Jesse; Holt, Ginger E.

2014-01-01

278

Balancing the rates of new bone formation and polymer degradation enhances healing of weight-bearing allograft/polyurethane composites in rabbit femoral defects.  

PubMed

There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling. PMID:23941405

Dumas, Jerald E; Prieto, Edna M; Zienkiewicz, Katarzyna J; Guda, Teja; Wenke, Joseph C; Bible, Jesse; Holt, Ginger E; Guelcher, Scott A

2014-01-01

279

The effect of dosage on the efficiency of LLLT in new bone formation at the expanded suture in rats.  

PubMed

The aim of this study was to investigate the effect that dosage has on the efficiency of low-level laser therapy (LLLT) in bone formation in a rat study model. Twenty-eight rats were divided into four groups as only expansion (OE), expansion?+?low dose (0.15 J) (LD), expansion?+?medium dose (0.65 J) (MD), and expansion?+?high dose (198 J) (HD) laser therapy groups. The midpalatal suture was expanded during 5 days. Afterwards, irradiations were started and performed with an 820 nm, continuous wave, Ga-Al-As diode laser (Doris, CTL-1106MX, Warsaw, Poland). At the end of experiment, the premaxillae of the animals were dissected. The sections were transferred into PC environment and analyzed by using Image Analysis program. Number of osteoblasts, osteoclasts, fibroblasts, vessels, transforming growth factor beta (TGF-?) expression, and new bone formation were evaluated with this program. Amount of expansion did not show any difference among the groups. All parameters except the number of osteoclasts were increased in all lased groups while that parameter was significantly decreased. Vessels, TGF-? expression, and new bone formation were mostly increased in LD group followed by HD group. Among the lased groups, a significant difference was observed only for the amount of new bone formation, which was between the LD and the MD groups. On the other hand, the difference in this parameter was insignificant between OE and MD groups. Low-level laser therapy with both 5 and 6,300 J/cm(2) doses was found to be significantly effective, while the 20 J/cm(2) dose did not show a significant effect in increasing new bone formation. This finding reveals that the efficiency of the therapy is affected by the dosage. PMID:25228094

Altan, Ayse Burcu; Bicakci, Ali Altug; Avunduk, Mustafa Cihat; Esen, Hasan

2015-01-01

280

Bone formation in vivo induced by Cbfa1-carrying adenoviral vectors released from a biodegradable porous ?-tricalcium phosphate (?-TCP) material  

NASA Astrophysics Data System (ADS)

Overexpression of Cbfa1 (a transcription factor indispensable for osteoblastic differentiation) is expected to induce the formation of bone directly and indirectly in vivo by accelerating osteoblastic differentiation. Adenoviral vectors carrying the cDNA of Cbfa1/til-1(Adv-Cbf1) were allowed to be adsorbed onto porous blocks of ?-tricalcium phosphate (?-TCP), a biodegradable ceramic, which were then implanted subcutaneously and orthotopically into bone defects. The adenoviral vectors were released sustainingly by biodegradation, providing long-term expression of the genes. Results of the subcutaneous implantation of Adv-Cbfa1-adsorbed ?-TCP/osteoprogenitor cells suggest that a larger amount of bone formed in the pores of the implant than in the control material. Regarding orthotopic implantation into bone defects, the released Adv-Cbfa1 accelerated regeneration in the cortical bone, whereas it induced bone resorption in the marrow cavity. A safer gene transfer using a smaller amount of the vector was achieved using biodegradable porous ?-TCP as a carrier.

Uemura, Toshimasa; Kojima, Hiroko

2011-06-01

281

Bone substitutes: new concepts  

Microsoft Academic Search

The filling of bone defects resulting from trauma or surgical resections of tumors requires bone grafts or bone substitutes. Bone substitute must be biocompatible, osteoconductive, and must present good mechanical properties. Among biomaterials classicaly used, calcium phosphate ceramic appear to be suitable alternatives to bone grafts. Calcium phosphate are known able to promote new bone formation on contact and have

D. Heymann; N. Passuti

1999-01-01

282

Bone formation by three-dimensional stromal osteoblast culture in biodegradable polymer scaffolds  

NASA Technical Reports Server (NTRS)

Bone formation was investigated in vitro by culturing stromal osteoblasts in three-dimensional (3-D), biodegradable poly(DL-lactic-co-glycolic acid) foams. Three polymer foam pore sizes, ranging from 150-300, 300-500, and 500-710 microns, and two different cell seeding densities, 6.83 x 10(5) cells/cm2 and 22.1 x 10(5) cells/cm2, were examined over a 56-day culture period. The polymer foams supported the proliferation of seeded osteoblasts as well as their differentiated function, as demonstrated by high alkaline phosphatase activity and deposition of a mineralized matrix by the cells. Cell number, alkaline phosphatase activity, and mineral deposition increased significantly over time for all the polymer foams. Osteoblast foam constructs created by seeding 6.83 x 10(5) cells/cm2 on foams with 300-500 microns pores resulted in a cell density of 4.63 x 10(5) cells/cm2 after 1 day in culture; they had alkaline phosphatase activities of 4.28 x 10(-7) and 2.91 x 10(-6) mumol/cell/min on Days 7 and 28, respectively; and they had a cell density that increased to 18.7 x 10(5) cells/cm2 by Day 56. For the same constructs, the mineralized matrix reached a maximum penetration depth of 240 microns from the top surface of the foam and a value of 0.083 mm for mineralized tissue volume per unit of cross sectional area. Seeding density was an important parameter for the constructs, but pore size over the range tested did not affect cell proliferation or function. This study suggests the feasibility of using poly(alpha-hydroxy ester) foams as scaffolding materials for the transplantation of autogenous osteoblasts to regenerate bone tissue.

Ishaug, S. L.; Crane, G. M.; Miller, M. J.; Yasko, A. W.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

1997-01-01

283

Bioglass ®45S5 Stimulates Osteoblast Turnover and Enhances Bone Formation In Vitro: Implications and Applications for Bone Tissue Engineering  

Microsoft Academic Search

.   We investigated the concept of using bioactive substrates as templates for in vitro synthesis of bone tissue for transplantation by assessing the osteogenic potential of a melt-derived bioactive glass ceramic\\u000a (Bioglass® 45S5) in vitro. Bioactive glass ceramic and bioinert (plastic) substrates were seeded with human primary osteoblasts and evaluated after\\u000a 2, 6, and 12 days. Flow cytometric analysis of

I. D. Xynos; M. V. J. Hukkanen; J. J. Batten; L. D. Buttery; L. L. Hench; J. M. Polak

2000-01-01

284

LAMELLAR MAGNETISM ASSOCIATED WITH NANOSCALE EXSOLUTION  

E-print Network

LAMELLAR MAGNETISM ASSOCIATED WITH NANOSCALE EXSOLUTION IN THE ILMENITE-HEMATITE SOLID SOLUTION-hematite (FeTiO3-Fe2O3) solid solution is one of the most important magnetic phases in nature. Unusual magnetic, magnetic ordering, and exsolution. This presentation describes how this interaction leads to the phenomenon

Dunin-Borkowski, Rafal E.

285

Lamellar macular hole after intravitreal ocriplasmin injection.  

PubMed

Intravitreal ocriplasmin was recently approved by the Food and Drug Administration to achieve medical vitreolysis in the setting of vitreomacular adhesion (VMA). We report a case of a 76-year-old woman who developed a lamellar macular hole following treatment with intravitreal ocriplasmin injection for VMA. A pathophysiological mechanism to explain this previously unreported complication of ocriplasmin injection is proposed. PMID:25576512

Chod, Ross Bronson; Goodrich, Clifford; Saxena, Sandeep; Akduman, Levent

2015-01-01

286

A new in vivo screening model for posterior spinal bone formation: comparison of ten calcium phosphate ceramic material treatments.  

PubMed

This study presents a new screening model for evaluating the influence of multiple conditions on the initial process of bone formation in the posterior lumbar spine of a large animal. This model uses cages designed for placement on the decorticated transverse process of the goat lumbar spine. Five conduction channels per cage, each be defined by a different material treatment, are open to both the underlying bone and overlying soft tissue. The model was validated in ten adult Dutch milk goats, with each animal implanted with two cages containing a total of ten calcium phosphate material treatments according to a randomized complete block design. The ten calcium phosphate ceramic materials were created through a combination of material chemistry (BCP, TCP, HA), sintering temperature (low, medium, high), calcination and surface roughness treatments. To monitor the bone formation over time, fluorochrome markers were administered at 3, 5 and 7 weeks and the animals were sacrificed at 9 weeks after implantation. Bone formation in the conduction channels was investigated by histology and histomorphometry of non-decalcified sections using traditional light and epifluorescent microscopy. According to both observed and measured bone formation parameters, materials were ranked in order of increasing magnitude as follows: low sintering temperature BCP (rough and smooth) approximately medium sintering temperature BCP approximately = TCP > calcined low sintering temperature HA > non-calcined low sintering temperature HA > high sintering temperature BCP (rough and smooth) > high sintering temperature HA (calcined and non-calcined). These results agree closely with those obtained in previous studies of osteoconduction and bioactivity of ceramics thereby validating the screening model presented in this study. PMID:16111745

Wilson, Clayton E; Kruyt, Moyo C; de Bruijn, Joost D; van Blitterswijk, Clemens A; Oner, F Cumhur; Verbout, Abraham J; Dhert, Wouter J A

2006-01-01

287

Emerging strategies and therapies for treatment of Paget's disease of bone.  

PubMed

Paget's disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone disorder after osteoporosis, affecting up to 3% of adults over 55 years of age. One of the most striking and intriguing clinical features is the focal nature of the disorder, in that once the disease is established within a bone, there is only local spread within that bone and no systemic dissemination. Despite many years of intense research, the etiology of PDB has still to be conclusively determined. Based on a detailed review of genetic and viral factors incriminated in PDB, we propose a unifying hypothesis from which we can suggest emerging strategies and therapies. PDB results in weakened bone strength and abnormal bone architecture, leading to pain, deformity or, depending on the bone involved, fracture in the affected bone. The diagnostic assessment includes serum total alkaline phosphatase, total body bone scintigraphy, skull and enlarged view pelvis x-rays, and if needed, additional x-rays. The ideal therapeutic option would eliminate bone pain, normalize serum total alkaline phosphatase with prolonged remission, heal radiographic osteolytic lesions, restore normal lamellar bone, and prevent recurrence and complications. With the development of increasingly potent bisphosphonates, culminating in the introduction of a single intravenous infusion of zoledronic acid 5 mg, these goals of treatment are close to being achieved, together with long-term remission in almost all patients. Based on the recent pathophysiological findings, emerging strategies and therapies are reviewed: ie, pulse treatment with zoledronic acid; denosumab, a fully human monoclonal antibody directed against RANK ligand; tocilizumab, an interleukin-6 receptor inhibitor; odanacatib, a cathepsin K inhibitor; and proteasome and Dickkopf-1 inhibitors. PMID:21607019

Michou, Laëtitia; Brown, Jacques P

2011-01-01

288

Effect of acemannan, an extracted polysaccharide from Aloe vera, on BMSCs proliferation, differentiation, extracellular matrix synthesis, mineralization, and bone formation in a tooth extraction model.  

PubMed

Aloe vera is a traditional wound healing medicine. We hypothesized acemannan, a polysaccharide extracted from Aloe vera gel, could affect bone formation. Primary rat bone marrow stromal cells (BMSCs) were treated with various concentrations of acemannan. New DNA synthesis, VEGF, BMP-2, alkaline phosphatase activity, bone sialoprotein, osteopontin expression, and mineralization were determined by [(3)H] thymidine incorporation assay, ELISA, biochemical assay, western blotting, and Alizarin Red staining, respectively. In an animal study, mandibular right incisors of male Sprague-Dawley rats were extracted and an acemannan treated sponge was placed in the socket. After 1, 2, and 4 weeks, the mandibles were dissected. Bone formation was evaluated by dual-energy X-ray absorptiometry and histopathological examination. The in vitro results revealed acemannan significantly increased BMSC proliferation, VEGF, BMP-2, alkaline phosphatase activity, bone sialoprotein and osteopontin expression, and mineralization. In-vivo results showed acemannan-treated groups had higher bone mineral density and faster bone healing compared with untreated controls. A substantial ingrowth of bone trabeculae was observed in acemannan-treated groups. These data suggest acemannan could function as a bioactive molecule inducing bone formation by stimulating BMSCs proliferation, differentiation into osteoblasts, and extracellular matrix synthesis. Acemannan could be a candidate natural biomaterial for bone regeneration. PMID:23315202

Boonyagul, Sani; Banlunara, Wijit; Sangvanich, Polkit; Thunyakitpisal, Pasutha

2014-07-01

289

[The mineralization of the regenerate and the hormonal regulation of bone formation during the treatment of a malunited diaphyseal fracture of the shin bones].  

PubMed

In 68 patients with imperfectly united fracture of the crural bones who underwent treatment with the use of the Ilizarov's method, the processes of mineralization of the osseous regenerate being formed were studied. The most rapid deposition of the mineral substances was noted in gradual elimination of a deformity. In shortening of an extremity, the rate of mineralization depended on a size of the elongation performed. Increase in content of the osteotropic hormones and cyclic. nucleotides was indicative of the presence of favourable conditions for formation of osseous regenerate in correction of angular deformity by means of the Ilizarov's method. PMID:7637292

Shevtsov, V I; Sveshnikov, A A; Boroda?kevich, R D; Ofitserova, N V; Obanina, N F

1994-01-01

290

Modulation of crystal formation by bone phosphoproteins: role of glutamic acid-rich sequences in the nucleation of hydroxyapatite by bone sialoprotein.  

PubMed Central

Bone sialoprotein (BSP) is a bone-specific glycoprotein containing phosphoserine and sulphotyrosine residues and regions of contiguous glutamic acid residues. Recent studies in this laboratory have shown that BSP is capable of nucleating the bone mineral hydroxyapatite in a steady-state agarose gel system. We show here that chemical modification of carboxylate groups abolishes the nucleation activity of BSP, but enzymic dephosphorylation has no effect. Formation of hydroxyapatite is also induced by poly(L-glutamic acid) and poly(D-glutamic acid), but not by poly(L-aspartic acid) or poly(L-lysine). Calreticulin, a muscle protein with short sequences of contiguous glutamic acid residues, also lacks nucleation activity. These findings suggest that the nucleation of hydroxyapatite by BSP involves one or both of the glutamic acid-rich sequences. Based on these findings and others, we propose that polycarboxylate sequences represent a general site for growth-modulating interactions between proteins and biological crystals. Images Figure 3 PMID:7915111

Hunter, G K; Goldberg, H A

1994-01-01

291

Ectopic bone formation cannot occur by hydroxyapatite/?-tricalcium phosphate bioceramics in green fluorescent protein chimeric mice  

NASA Astrophysics Data System (ADS)

Many studies have shown that calcium phosphate ceramics (CP) have osteoconductive and osteoinductive properties; however, the exact mechanism of bone induction has not yet been reported. This study was performed to investigate if destroying immunological function will influence osteogenesis, to explain the mechanism which is unclear. In this study, twenty C57BL/6 mice were divided into two groups (n = 10), in group 1, a hydroxyapatite/?-tricalcium phosphate (HA/?-TCP) ceramic was implanted into both the left and right leg muscles of each mouse; in group 2, ten mice experienced lethal irradiation, then were injected bone marrow (BM) cells from green fluorescent protein (GFP) transgenic mice by tail veil, after bone marrow transplantation (BMT), heart, liver, spleen, lung, kidney, and muscle were harvested for biological analysis, after the GFP chimera model was established successfully, the same HA/?-TCP ceramic was implanted into both leg muscles of each mouse immediately after irradiation. 45 and 90 days after implantation, the ceramics of the two groups were harvested to perform with hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining; the results showed that there was no bone formation in group 2, while new bone tissues were detected in group 1. Our findings suggest that the BM cell from GFP transgenic mice is a good biomarker and it could set a good platform for chimera model; it also shows that BM cell is one of cell resources of bone induction, and destruction of immune function will impede osteoinduction by CP. Overall, our results may shed light on clear mechanism study of bone induction in the future.

Cheng, Lijia; Duan, Xin; Xiang, Zhou; Shi, Yujun; Lu, Xiaofeng; Ye, Feng; Bu, Hong

2012-12-01

292

Divergent Resorbability and Effects on Osteoclast Formation of Commonly Used Bone Substitutes in a Human In Vitro-Assay  

PubMed Central

Bioactive bone substitute materials are a valuable alternative to autologous bone transplantations in the repair of skeletal defects. However, clinical studies have reported varying success rates for many commonly used biomaterials. While osteoblasts have traditionally been regarded as key players mediating osseointegration, increasing evidence suggests that bone-resorbing osteoclasts are of crucial importance for the longevity of applied biomaterials. As no standardized data on the resorbability of biomaterials exists, we applied an in vitro-assay to compare ten commonly used bone substitutes. Human peripheral blood mononuclear cells (PBMCs) were differentiated into osteoclasts in the co-presence of dentin chips and biomaterials or dentin alone (control) for a period of 28 days. Osteoclast maturation was monitored on day 0 and 14 by light microscopy, and material-dependent changes in extracellular pH were assessed twice weekly. Mature osteoclasts were quantified using TRAP stainings on day 28 and their resorptive activity was determined on dentin (toluidin blue staining) and biomaterials (scanning electron microscopy, SEM). The analyzed biomaterials caused specific changes in the pH, which were correlated with osteoclast multinuclearity (r?=?0.942; p?=?0.034) and activity on biomaterials (r?=?0.594; p?=?0.041). Perossal led to a significant reduction of pH, nuclei per osteoclast and dentin resorption, whereas Tutogen bovine and Tutobone human strikingly increased all three parameters. Furthermore, natural biomaterials were resorbed more rapidly than synthetic biomaterials leading to differential relative resorption coefficients, which indicate whether bone substitutes lead to a balanced resorption or preferential resorption of either the biomaterial or the surrounding bone. Taken together, this study for the first time compares the effects of widely used biomaterials on osteoclast formation and resorbability in an unbiased approach that may now aid in improving the preclinical evaluation of bone substitute materials. PMID:23071629

Busse, Björn; Schilling, Arndt F.; Schinke, Thorsten; Amling, Michael; Lange, Tobias

2012-01-01

293

Total extract of Korean red ginseng facilitates human bone marrow hematopoietic colony formation in vitro  

PubMed Central

Background The number of CD34+ cells in a peripheral blood stem cell collection is the key factor in predicting successful treatment of hematologic malignancies. Korean Red Ginseng (KRG) (Panax ginseng C.A. Meyer) is the most popular medicinal herb in Korea. The objective of this study was to determine the effect of KRG on hematopoietic colony formation. Methods Bone marrow (BM) samples were obtained from 8 human donors after acquiring informed consent. BM mononuclear cells (MNCs) were isolated, and CD34+ cells were sorted using magnetic beads. The sorted CD34+ cells were incubated with or without total extract of KRG (50 µg/mL, 100 µg/mL) or Ginsenoside Rg1 (100 µg/mL), and the hematopoietic colony assay was performed using methylcellulose semisolid medium. The CD34+ cell counts were measured by a single platform assay using flow cytometry. Results The numbers of human BM-MNCs and CD34+ cells obtained after purification were variable among donors (5.6×107 and 1.3-48×107 and 8.9×104 and 1.8-80×104, respectively). The cells expanded 1,944 times after incubation for 12 d. Total extract of KRG added to the hematopoietic stem cell (HSC)-specific medium increased CD34+ cell counts 3.6 times compared to 2.6 times when using HSC medium alone. Total numbers of hematopoietic colonies in KRG medium were more than those observed in conventional medium, especially that of erythroid colonies such as burst forming unit-erythroid. Conclusion Total extract of KRG facilitated CD34+ cell expansion and hematopoietic colony formation, especially of the erythroid lineage. PMID:25325037

Kim, Sang-Gyung; Bae, Sung Hwa; Kim, Seong-Mo; Lee, Ji-Hye; Kim, Min Ji; Jang, Hae-Bong

2014-01-01

294

Bone Mesenchymal Stem Cells Contributed to the Neointimal Formation after Arterial Injury  

PubMed Central

Objectives Recent findings suggest that in response to repair-to-injury bone marrow mesenchymal stem cells (BMSCs) participate in the process of angiogenesis. It is unclear what role BMSCs play in the structure of the vessel wall. In present study, we aimed to determine whether BMSCs had the capacity of endothelial cells (ECs). Methods BMSCs were separated and cultured. FACS and RT-PCR analysis confirmed the gene expression phenotype. The capacity of migration and adhesion and the ultrastructure of BMSCs were examined. The effect of BMSCs transplantation on the vascular repair was investigated in a murine carotid artery-injured model. Results BMSCs could express some markers and form the tube-like structure. The migration and adhesion capacity of BMSCs increased significantly after stimulated. In addition, BMSCs had the intact cell junction. In vivo the local transfer of BMSCs differentiated into neo-endothelial cells in the injury model for carotid artery and contributed to the vascular remodeling. Conclusion These results showed that BMSCs could contribute to neointimal formation for vascular lesion and might be associated with the differentiation into ECs, which indicated the important therapeutic implications for vascular diseases. PMID:24349351

Li, Mincai; Li, Suqin; Yu, Liangzhu; Wu, Jiliang; She, Tonghui; Gan, Yaping; Hu, Zhenwu; Liao, Wenli; Xia, Hongli

2013-01-01

295

Ascorbic acid insufficiency induces the severe defect on bone formation via the down-regulation of osteocalcin production  

PubMed Central

The L-gulono-?-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo-/- mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo-/- mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo-/- mice, 3-week ascorbic acid-insufficient Gulo-/- mice, and 4-week ascorbic acid-insufficient Gulo-/- mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo-/- mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo-/- mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo-/- mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo-/-. In summary, ascorbic acid insufficiency in Gulo-/- mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels. PMID:24386598

Kim, Won; Bae, Seyeon; Kim, Hyemin; Kim, Yejin; Choi, Jiwon; Lim, Sun Young; Lee, Hei Jin; Lee, Jihyuk; Choi, Jiyea; Jang, Mirim; Lee, Kyoung Eun; Chung, Sun G.; Hwang, Young-il

2013-01-01

296

Incorporation of raloxifene-impregnated allograft around orthopedic titanium implants impairs early fixation but improves new bone formation.  

PubMed

Background - The anti-osteoporotic drug raloxifene reduces the risk of vertebral fractures by increasing bone mass density. We investigated whether raloxifene offers any benefits in augmenting early fixation of orthopedic implants in the setting of impaction bone grafting. Methods - 24 non-weight-bearing grafted gap implants were inserted bilaterally into the tibia of 12 dogs. The 2.5-mm peri-implant gap was filled with either raloxifene-impregnated or untreated bone allograft. Implants were harvested after 28 days. Implant fixation was assessed by mechanical testing and histomorphometric evaluation. Results - Raloxifene-treated allograft reduced early implant fixation compared to untreated allograft, as measured by inferior maximum shear strength (p < 0.001) and apparent shear stiffness (p = 0.001). We found that the raloxifene group had more newly formed bone in the gap around the implant (p = 0.02), but also less allograft (p = 0.03). Interpretation - The accelerated allograft resorption in the raloxifene group explained the impaired early fixation, despite its stimulation of new bone formation. Our results with local and possible high-dose treatment are not consistent with current theory regarding the mechanism of how systemic raloxifene administration counteracts the decrease in BMD in postmenopausal women. Instead of being solely anti-resorptive as generally held, our results indicate a possible anabolic side of raloxifene. PMID:25175661

Hermansen, Lars L; Sørensen, Mette; Barckman, Jeppe; Bechtold, Joan E; Søballe, Kjeld; Baas, Jørgen

2015-02-01

297

Total body irradiation is permissive for mesenchymal stem cell-mediated new bone formation following local transplantation.  

PubMed

Skeletal injury is a major clinical challenge accentuated by the decrease of bone marrow-derived mesenchymal stem/stromal cells (BMSCs) with age or disease. Numerous experimental and clinical studies have revealed that BMSCs hold great promise for regenerative therapies due to their direct osteogenic potential and indirect trophic/paracrine actions. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in modulating the host response to the injury. Common problems with BMSC therapy include poor cell engraftment, which can be addressed by total body irradiation (TBI) prior to transplantation. In this study, we tested the hypothesis that direct tibial transplantation of BMSCs drives endogenous bone formation in a dose-dependent manner, which is enhanced by TBI, and investigated the potential role of SDF-1 in facilitating these events. We found that TBI is permissive for transplanted BMSCs to engraft and contribute to new bone formation. Bone marrow (BM) interstitial fluid analysis revealed no differences of SDF-1 splice variants in irradiated animals compared to controls, despite the increased mRNA and protein levels expressed in whole BM cells. This correlated with increased dipeptidyl peptidase IV activity and the failure to induce chemotaxis of BMSCs in vitro. We found increased mRNA expression levels of the major SDF-1-cleaving proteases in whole BM cells from irradiated animals suggesting distinct spatial differences within the BM in which SDF-1 may play different autocrine and paracrine signaling roles beyond the immediate cell surface microenvironment. PMID:24914464

Herberg, Samuel; Kondrikova, Galina; Hussein, Khaled A; Periyasamy-Thandavan, Sudharsan; Johnson, Maribeth H; Elsalanty, Mohammed E; Shi, Xingming; Hamrick, Mark W; Isales, Carlos M; Hill, William D

2014-12-01

298

Self-assembly of lamellar- and cylinder-forming diblock copolymers in planar slits: insight from dissipative particle dynamics simulations.  

PubMed

We present a dissipative particle dynamics simulation study on nanostructure formation of symmetric and asymmetric diblock copolymers confined between planar surfaces. We consider symmetric and slightly asymmetric diblock copolymers that form lamellar nanostructures in the bulk, and highly asymmetric diblock copolymers that form cylindrical nanostructures in the bulk. The formation of the diblock copolymer nanostructures confined between the planar surfaces is investigated and characterized by varying the separation width and the strength of the interaction between the surfaces and the diblock copolymers. Both the slit width and the surface interaction strongly influence the phase diagram, especially for the asymmetric systems. For the symmetric and slightly asymmetric diblock copolymer systems, the confinement primarily affects the orientation of the lamellar domains and only marginally influences the domain morphologies. These systems form parallel lamellar phases with different number of lamellae, and perpendicular and mixed lamellar phases. In a narrow portion of the phase diagram, these systems exhibit a parallel perforated lamellar phase, where further insight into the appearance of this phase is provided through free-energy calculations. The confined highly asymmetric diblock copolymer system shows, in addition to nanostructures with parallel and perpendicular cylinders, noncylindrical structures such as parallel lamellae and parallel perforated lamellae. The formation of the various confined nanostructures is further analyzed by calculating structural characteristics such as the mean square end-to-end distance of the diblock copolymers and the nematic order parameter. PMID:20795714

Petrus, Pavel; Lísal, Martin; Brennan, John K

2010-09-21

299

Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery  

NASA Technical Reports Server (NTRS)

Porous biodegradable poly(DL-lactic-co-glycolic acid) foams were seeded with rat marrow stromal cells and implanted into the rat mesentery to investigate in vivo bone formation at an ectopic site. Cells were seeded at a density of 6.83 x 10(5) cells/cm2 onto polymer foams having pore sizes ranging from either 150 to 300 to 710 microns and cultured for 7 days in vitro prior to implantation. The polymer/cell constructs were harvested after 1, 7, 28, or 49 days in vivo and processed for histology and gel permeation chromatography. Visual observation of hematoxylin and eosin-stained sections and von Kossa-stained sections revealed the formation of mineralized bonelike tissue in the constructs within 7 days postimplantation. Ingrowth of vascular tissue was also found adjacent to the islands of bone, supplying the necessary metabolic requirements to the newly formed tissue. Mineralization and bone tissue formation were investigated by histomorphometry. The average penetration depth of mineralized tissue in the construct ranged from 190 +/- 50 microns for foams with 500-710-microns pores to 370 +/- 160 microns for foams with 150-300-microns pores after 49 days in vivo. The mineralized bone volume per surface area and total bone volume per surface area had maximal values of 0.28 +/- 0.21 mm (500-710-microns pore size, day 28) and 0.038 +/- 0.024 mm (150-300-microns, day 28), respectively. As much as 11% of the foam volume penetrated by bone tissue was filled with mineralized tissue. No significant trends over time were observed for any of the measured values (penetration depth, bone volume/surface area, or percent mineralized bone volume). These results suggest the feasibility of bone formation by osteoblast transplantation in an orthotopic site where not only bone formation from transplanted cells but also ingrowth from adjacent bone may occur.

Ishaug-Riley, S. L.; Crane, G. M.; Gurlek, A.; Miller, M. J.; Yasko, A. W.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

1997-01-01

300

Gap junction proteins exhibit early and specific expression during intramembranous bone formation in the developing chick mandible  

Microsoft Academic Search

The spatial and temporal expression of three closely related members of the connexin family of gap junction proteins (connexin42, Cx42; connexin43, Cx43; and connexin45, Cx45) was evaluated during bone formation in the mandibular process of the chick embryo. Mandibles of chick embryos from Hamburger and Hamilton stage 25 (approximately 5 days) through 19 days of development were dissected, serially sectioned

R. Minkoff; V. R. Rundus; S. B. Parker; E. L. Hertzberg; J. G. Laing; E. C. Beyer

1994-01-01

301

Freezing and melting water in lamellar structures.  

PubMed Central

The manner in which ice forms in lamellar suspensions of dielaidoylphosphatidylethanolamine, dielaidoylphosphatidylcholine, and dioleoylphosphatidylcholine in water depends strongly on the water fraction. For weight fractions between 15 and 9%, the freezing and melting temperatures are significantly depressed below 0 degree C. The ice exhibits a continuous melting transition spanning as much as 20 degrees C. When the water weight fraction is below 9%, ice never forms at temperatures as low as -40 degrees C. We show that when water contained in a lamellar lipid suspension freezes, the ice is not found between the bilayers; it exists as pools of crystalline ice in equilibrium with the bound water associated with the polar lipid headgroups. We have used this effect, together with the known chemical potential of ice, to measure hydration forces between lipid bilayers. We find exponentially decaying hydration repulsion when the bilayers are less than about 7 A apart. For larger separations, we find significant deviations from single exponential decay. PMID:7948683

Gleeson, J T; Erramilli, S; Gruner, S M

1994-01-01

302

Optimal lamellar arrangement in fish gills  

PubMed Central

Fish respire through gills, which have evolved to extract aqueous oxygen. Fish gills consist of filaments with well-ordered lamellar structures, which play a role in maximizing oxygen diffusion. It is interesting that when we anatomically observe the gills of various fish species, gill interlamellar distances (d) vary little among them, despite large variations in body mass (Mb). Noting that the small channels formed by densely packed lamellae cause significant viscous resistance to water flow, we construct and test a model of oxygen transfer rate as a function of the lamellar dimensions and pumping pressure, which allows us to predict the optimal interlamellar distance that maximizes the oxygen transfer rate in the gill. Comparing our theory with biological data supports the hypothesis that fish gills have evolved to form the optimal interlamellar distances for maximizing oxygen transfer. This explains the weak scaling dependence of d on Mb: d ? Mb1/6. PMID:24847065

Park, Keunhwan; Kim, Wonjung; Kim, Ho-Young

2014-01-01

303

Castor oil polymer induces bone formation with high matrix metalloproteinase-2 expression.  

PubMed

The aim of this study was to evaluate the modulation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) expression in newly formed bone tissue at the interface between implants derived from castor oil (Ricinus communis) polymer and the tibia medullary canal. Forty-four rabbits were assigned to either Group 1 (n?=?12; control) or Group 2 (n?=?30), which had the tibial medullary canals reamed bilaterally and filled with polymer. CT scans showed no space between the material surface and the bone at the implant/bone marrow interface, and the density of the tissues at this interface was similar to the density measured of other regions of the bone. At 90 days postimplantation, the interface with the polymer presented a thick layer of newly formed bone tissue rich in osteocytes. This tissue exhibited ongoing maturation at 120 and 150 days postimplantation. Overall, bone remodeling process was accompanied by positive modulation of MMP-2 and low MMP-9 expression. Differently, in control group, the internal surface close to the medullary canal was lined by osteoblasts, followed by a bone tissue zone with few lacunae filled with osteocytes. Maturation of the tissue of the medullary internal surface occurred in the inner region, with the bone being nonlamellar. PMID:23670892

Saran, Wallace Rocha; Chierice, Gilberto Orivaldo; da Silva, Raquel Assed Bezerra; de Queiroz, Alexandra Mussolino; Paula-Silva, Francisco Wanderley Garcia; da Silva, Léa Assed Bezerra

2014-02-01

304

Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation  

Microsoft Academic Search

Cleft palate, including submucous cleft palate, is among the most common birth defects in humans. While overt cleft palate results from defects in growth or fusion of the developing palatal shelves, submucous cleft palate is characterized by defects in palatal bones. In this report, we show that the Bmpr1a gene, encoding a type I receptor for bone morphogenetic proteins (Bmp),

Jin-A. Baek; Yu Lan; Han Liu; Kathleen M. Maltby; Yuji Mishina; Rulang Jiang

2011-01-01

305

Gene delivery of c-myb increases bone formation surrounding oral implants.  

PubMed

Bone regeneration around titanium (Ti) implants is a relatively slow process. The c-myb transcription factor has been associated with high proliferation and differentiation rates in bone. This study analyzed whether c-myb can enhance new bone surrounding the implant. In vitro overexpressed chitosan-gold nanoparticles conjugated with plasmid DNA/c-myb (Ch-GNPs/c-myb)-coated Ti surfaces were associated with enhanced expression of the osteogenic molecules osteopontin (OPN), runt-related transcription factor 2 (RUNX-2), and bone morphogenetic proteins (BMP2/7) in MC-3T3E1 osteoblast cells. Further, to determine its in vivo effect, we inserted Ch-GNPs/c-myb-coated Ti implants into rat mandibles. One and 4 wks post-implantation, mandibles were examined by microcomputed tomography, immunohistochemistry, and hematoxylin & eosin staining. The microcomputed tomography analysis demonstrated that c-myb overexpression increased the density and volume of newly formed bone surrounding the implants, compared with those in controls (p < .05). Further, c-myb increased the number of cells expressing BMP2/7 and aided in the increase of new bone (p < .05). These results support the view that c-myb overexpression accelerates new bone surrounding implants and can serve as a potent molecule in promoting tissue regeneration around dental implants. The recipient rat used in this system provides an excellent in vivo model for studies of bone regeneration. PMID:23838059

Bhattarai, G; Lee, Y H; Lee, M H; Yi, H K

2013-09-01

306

Effects of JSOG-6 on protection against bone loss in ovariectomized mice through regulation of osteoblast differentiation and osteoclast formation  

PubMed Central

Background JSOG-6 is used as a traditional medicine to relieve the symptoms associated with inflammation, rheumatism, and osteoporosis in Korea. In the present study, we investigated the effects of JSOG-6 on bone loss prevention both in in vitro and in vivo as well as its underlying mechanism of action. Methods Protection against bone loss was assessed in an ovariectomized (OVX) mouse model. Bone microarchitecture was measured using a micro-computed tomography to detect the parameters of three-dimensional structure of a trabecular bone. Serum biomarkers were also evaluated in an OVX-induced model. Osteoclasts derived from mouse bone marrow cells (BMCs) and osteoblastic MC3T3-E1 cells were also employed to investigate the mechanism of action. Results Oral administration of JSOG-6 significantly increased the bone mineral density (BMD) of the femur in OVX mice in vivo. Especially, the reduced Tb.No (trabecular bone number) in the OVX group was significantly recovered by JSOG-6 treatment. The serum levels of alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase, biomarkers of bone resorption, were significantly elevated in OVX mice, but JSOG-6 effectively inhibited the increase in OVX mice. JSOG-6 was also found to enhance the osteoblastic differentiation and maturation with the increase of the density and ALP activity, a marker of osteoblastic differentiation, as well as calcium deposition, a marker of osteoblastic maturation in MC3T3-E1 cells. The effects of JSOG-6 on osteoblastic differentiation were also associated in part with the increase of ALP and OPN mRNA expressions and the decrease of RANKL mRNA expression in MC3T3-E1 cells. Conclusions The findings demonstrate that JSOG-6 induced protection against bone loss in OVX mice, and its anti-osteoporotic property might be, in part, a function of the stimulation of osteoblast differentiation and the inhibition of osteoclast formation. These findings suggest that JSOG-6 might be an applicable therapeutic traditional medicine for the regulation of the osteoporotic response. PMID:24903150

2014-01-01

307

Culture medium of bone marrow-derived human mesenchymal stem cells effects lymphatic endothelial cells and tumor lymph vessel formation  

PubMed Central

Human bone marrow mesenchymal stem cells (hBM-MSCs) favor tumor growth and metastasis in vivo and in vitro. Neovascularization is involved in several pathological conditions, including tumor growth and metastasis. Previous studies have demonstrated that human bone marrow MSC-derived conditioned medium (hBM-MSC-CM) can promote tumor growth by inducing the expression of vascular epidermal growth factor (VEGF) in tumor cells. However, the effect of BM-MSCs on tumor lymph vessel formation has yet to be elucidated. In the present study, the effect of BM-MSCs on processes involved in lymph vessel formation, including tube formation, migration and proliferation, was investigated in human-derived lymphatic endothelial cells (HDLECs). It was identified that hBM-MSC-CM promoted the tube formation and migration of HDLECs. In addition, tumor cells were revealed to participate in lymph vessel formation. In the present study, the SGC-7901, HGC-27 and GFP-MCF-7 cell lines were treated with hBM-MSC-CM. The results demonstrated that the expression of the lymph-associated markers, prospero homeobox protein 1 and VEGF receptor-3, were increased in the SGC-7901 and HGC-27 cell lines, but not in the GFP-MCF-7 cells. The tube formation assay demonstrated that the HGC-27 cells treated with hBM-MSC-CM for 20 days underwent tube formation. These findings indicate that hBM-MSC-CM can promote tube formation in HDLECs and HGC-27 cells, which may be associated with lymph vessel formation during tumor growth and metastasis. PMID:25663886

ZHAN, JIE; LI, YAHONG; YU, JING; ZHAO, YUANYAUN; CAO, WENMING; MA, JIE; SUN, XIAOXIAN; SUN, LI; QIAN, HUI; ZHU, WEI; XU, WENRONG

2015-01-01

308

A New Piezoelectric Actuator Induces Bone Formation In Vivo: A Preliminary Study  

PubMed Central

This in vivo study presents the preliminary results of the use of a novel piezoelectric actuator for orthopedic application. The innovative use of the converse piezoelectric effect to mechanically stimulate bone was achieved with polyvinylidene fluoride actuators implanted in osteotomy cuts in sheep femur and tibia. The biological response around the osteotomies was assessed through histology and histomorphometry in nondecalcified sections and histochemistry and immunohistochemistry in decalcified sections, namely, through Masson's trichrome, and labeling of osteopontin, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. After one-month implantation, total bone area and new bone area were significantly higher around actuators when compared to static controls. Bone deposition rate was also significantly higher in the mechanically stimulated areas. In these areas, osteopontin increased expression was observed. The present in vivo study suggests that piezoelectric materials and the converse piezoelectric effect may be used to effectively stimulate bone growth. PMID:22701304

Reis, Joana; Frias, Clara; Canto e Castro, Carlos; Botelho, Maria Luísa; Marques, António Torres; Simões, José António Oliveira; Capela e Silva, Fernando; Potes, José

2012-01-01

309

A new piezoelectric actuator induces bone formation in vivo: a preliminary study.  

PubMed

This in vivo study presents the preliminary results of the use of a novel piezoelectric actuator for orthopedic application. The innovative use of the converse piezoelectric effect to mechanically stimulate bone was achieved with polyvinylidene fluoride actuators implanted in osteotomy cuts in sheep femur and tibia. The biological response around the osteotomies was assessed through histology and histomorphometry in nondecalcified sections and histochemistry and immunohistochemistry in decalcified sections, namely, through Masson's trichrome, and labeling of osteopontin, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. After one-month implantation, total bone area and new bone area were significantly higher around actuators when compared to static controls. Bone deposition rate was also significantly higher in the mechanically stimulated areas. In these areas, osteopontin increased expression was observed. The present in vivo study suggests that piezoelectric materials and the converse piezoelectric effect may be used to effectively stimulate bone growth. PMID:22701304

Reis, Joana; Frias, Clara; Canto e Castro, Carlos; Botelho, Maria Luísa; Marques, António Torres; Simões, José António Oliveira; Capela e Silva, Fernando; Potes, José

2012-01-01

310

Chemical functionalization of bone implants with nanoparticle-stabilized chitosan and methotrexate for inhibiting both osteoclastoma formation and bacterial infection.  

PubMed

A great challenge in orthopedic tumor operation faced by orthopedic implants is the high recurrence and metastasis of bone tumor as well as the bacterial infection associated with the implants. Thus ideal titanium (Ti)-based bone implants should be able to not only inhibit cancer cell adhesion and proliferation, promote cancer cell apoptosis, but also resist bacterial infections. Towards this end, we developed a new approach to modify the surface of Ti-based bone implants so that they can restrain functions of osteoclastoma (Giant cell tumor of bone) cancer cells (GCTs) and inhibit the adhesion of bacteria. First, the surface of pristine Ti substrates was functionalized with dopamine (DA) to form DA-Ti substrates. Then nanoparticles electrostatically assembled from poly-lysine (PLL) and heparin (Hep) were chemically immobilized onto the DA-Ti substrates to form PLL/Hep-Ti substrates. Chitosan (CH) and methotrexate (MTX) were then electrostatically immobilized onto the PLL/Hep-Ti substrates to generate CH-MTX-Ti substrates. The successful functionalization of the Ti substrates was confirmed by X-ray photoelectron spectroscopy. GCTs cultured on differently functionalized Ti substrates were investigated in terms of cell adhesion, cytoskeleton, proliferation, cytotoxicity and apoptosis. The growth of Staphylococcus aureus bacteria in the presence of different substrates was also assayed. Our results showed that CH-MTX-Ti substrates not only significantly inhibited the adhesion, proliferation and viability of GCTs, promoted the apoptosis of GCTs, but also prevented the adhesion of the bacteria and the subsequent formation of bacterial biofilms, when compared to other Ti substrates. Thus CH-MTX-Ti substrates are expected to be used as orthopedic prostheses in bone tumor surgery that can inhibit both osteoclastoma formation and bacterial infections. PMID:25177491

Li, Li-Hua; Li, Mei; Li, Dan; He, Peng; Xia, Hong; Zhang, Yu; Mao, Chuanbin

2014-09-28

311

Mesenchymal stem cell expression of stromal cell-derived factor-1? augments bone formation in a model of local regenerative therapy.  

PubMed

Bone has the potential for spontaneous healing. However, this process often fails in patients with co-morbidities requiring clinical intervention. Numerous studies have revealed that bone marrow-derived mesenchymal stem/stromal cells (BMSCs) hold great potential for regenerative therapies. Common problems include poor cell engraftment, which can be addressed by irradiation prior to transplantation. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in bone formation. However, osteogenic contributions of the beta splice variant of SDF-1 (SDF-1?), which is highly expressed in bone, remain unclear. Using the tetracycline (Tet)-regulatory system we have shown that SDF-1? enhances BMSC osteogenic differentiation in vitro. Here we test the hypothesis that SDF-1? augments bone formation in vivo in a model of local BMSC transplantation following irradiation. We found that SDF-1?, expressed at high levels in Tet-Off-SDF-1? BMSCs, augments the cell-mediated therapeutic effects resulting in enhanced bone formation, as evidenced by ex vivo ?CT and bone histomorphometry. The data demonstrate the specific contribution of SDF-1? to BMSC-mediated bone formation, and validate the feasibility of the Tet-Off technology to regulate SDF-1? expression in vivo. In conclusion, SDF-1? provides potent synergistic effects supporting BMSC-mediated bone formation and appears a suitable candidate for optimization of bone augmentation in translational protocols. Published 2014. This article has been contributed to by US Government employees and their work is in the public domain in the USA. J Orthop Res 33:174-184, 2015. PMID:25351363

Herberg, Samuel; Kondrikova, Galina; Hussein, Khaled A; Johnson, Maribeth H; Elsalanty, Mohammed E; Shi, Xingming; Hamrick, Mark W; Isales, Carlos M; Hill, William D

2015-02-01

312

Stimulation of Bone Formation in Cortical Bone of Mice Treated with a Receptor Activator of Nuclear Factor-?B Ligand (RANKL)-binding Peptide That Possesses Osteoclastogenesis Inhibitory Activity  

PubMed Central

To date, parathyroid hormone is the only clinically available bone anabolic drug. The major difficulty in the development of such drugs is the lack of clarification of the mechanisms regulating osteoblast differentiation and bone formation. Here, we report a peptide (W9) known to abrogate osteoclast differentiation in vivo via blocking receptor activator of nuclear factor-?B ligand (RANKL)-RANK signaling that we surprisingly found exhibits a bone anabolic effect in vivo. Subcutaneous administration of W9 three times/day for 5 days significantly augmented bone mineral density in mouse cortical bone. Histomorphometric analysis showed a decrease in osteoclastogenesis in the distal femoral metaphysis and a significant increase in bone formation in the femoral diaphysis. Our findings suggest that W9 exerts bone anabolic activity. To clarify the mechanisms involved in this activity, we investigated the effects of W9 on osteoblast differentiation/mineralization in MC3T3-E1 (E1) cells. W9 markedly increased alkaline phosphatase (a marker enzyme of osteoblasts) activity and mineralization as shown by alizarin red staining. Gene expression of several osteogenesis-related factors was increased in W9-treated E1 cells. Addition of W9 activated p38 MAPK and Smad1/5/8 in E1 cells, and W9 showed osteogenesis stimulatory activity synergistically with BMP-2 in vitro and ectopic bone formation. Knockdown of RANKL expression in E1 cells reduced the effect of W9. Furthermore, W9 showed a weak effect on RANKL-deficient osteoblasts in alkaline phosphatase assay. Taken together, our findings suggest that this peptide may be useful for the treatment of bone diseases, and W9 achieves its bone anabolic activity through RANKL on osteoblasts accompanied by production of several autocrine factors. PMID:23319583

Furuya, Yuriko; Inagaki, Atsushi; Khan, Masud; Mori, Kaoru; Penninger, Josef M.; Nakamura, Midori; Udagawa, Nobuyuki; Aoki, Kazuhiro; Ohya, Keiichi; Uchida, Kohji; Yasuda, Hisataka

2013-01-01

313

Etanercept Promotes Bone Formation via Suppression of Dickkopf-1 Expression in Rats with Collagen-Induced Arthritis  

PubMed Central

Background Various clinical reports suggest etanercept (ETN) has some efficacy in bone formation in rheumatoid arthritis (RA). To examine this effect, we investigated the gene expression of cytokines relevant to osteoblast/osteoclast differentiation, and evaluated histomorphometric findings in mature rats with collagen-induced arthritis (CIA). Methods Total RNA was extracted from knee joints with CIA after ETN or placebo administration. Subsequently, realtime-PCR was carried out to quantify the mRNAs encoding Wnt-1, Dickkopf-1 (DKK-1), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegelin (OPG) and TNF (tumor necrosis factor)-alpha. In histomorphometric analysis, the infiltrating pannus volume and pannus surface, and the following items in contact with pannus surface were measured: osteoclast number, osteoid surface, osteoid volume and labeling surface. These were evaluated in the distal femur with CIA with or without ETN administration. Results TNF-alpha, RANKL and OPG mRNA expressions, linked to osteoclastogenesis, were not significantly different with or without ETN administration. ETN administration significantly increased Wnt-1 mRNA expression, the osteoblast promoter, and decreased DKK-1 mRNA expression, the Wnt signal inhibitor. In histomorphometric analysis, pannus volume, pannus surface and osteoclast number, parameters of bone destruction, were not significantly different among groups. Osteoid volume, osteoid surface and labeling surface, parameters of bone formation, increased significantly with ETN administration. Conclusion Our results suggest that ETN suppresses DDK-1 expression, and, as a result, Wnt expression is promoted and osteoblastogenesis becomes more active, independent of the regulation of osteoclast activity. Marked bone formation is attributed to the fact that ETN directly promotes osteoblastogenesis, not as a result of suppressing osteoclastogenesis. PMID:24031147

Tanida, Atsushi; Kishimoto, Yuji; Okano, Toru; Hagino, Hiroshi

2013-01-01

314

Ectopic bone formation by 3D porous calcium phosphate-Ti6Al4V hybrids produced by perfusion electrodeposition.  

PubMed

Successful clinical repair of non-healing skeletal defects requires the use of bone substitutes with robust bone inductivity and excellent biomechanical stability. Thus, three-dimensionally functionalised porous calcium phosphate-Ti6Al4V (CaP-Ti) hybrids were produced by perfusion electrodeposition, and the in vitro and in vivo biological performances were evaluated using human periosteum derived cells (hPDCs). By applying various current densities at the optimised deposition conditions, CaP coatings with sub-micrometer to nano-scale porous crystalline structures and different ion dissolution kinetics were deposited on the porous Ti6Al4V scaffolds. These distinctive physicochemical properties caused a significant impact on in vitro proliferation, osteogenic differentiation, and matrix mineralisation of hPDCs. This includes a potential role of hPDCs in mediating osteoclastogenesis for the resorption of CaP coatings, as indicated by a significant down-regulation of osteoprotegerin (OPG) gene expression and by the histological observation of abundant multi-nucleated giant cells near to the coatings. By subcutaneous implantation, the produced hybrids induced ectopic bone formation, which was highly dependent on the physicochemical properties of the CaP coating (including the Ca(2+) dissolution kinetics and coating surface topography), in a cell density-dependent manner. This study provided further insight on stem cell-CaP biomaterial interactions, and the feasibility to produced bone reparative units that are predictively osteoinductive in vivo by perfusion electrodeposition technology. PMID:22381474

Chai, Yoke Chin; Kerckhofs, Greet; Roberts, Scott J; Van Bael, Simon; Schepers, Evert; Vleugels, Jozef; Luyten, Frank P; Schrooten, Jan

2012-06-01

315

Bone grafts in dentistry  

PubMed Central

Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation. PMID:23946565

Kumar, Prasanna; Vinitha, Belliappa; Fathima, Ghousia

2013-01-01

316

Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol.  

PubMed

Aryl hydrocarbon receptor (AhR) ligands are environmental contaminants found in cigarette smoke and other sources of air pollution. The prototypical compound is TCDD (2,3,7, 8-tetrachlorodibenzo-p-dioxin), also known as dioxin. There is an increasing body of knowledge linking cigarette smoking to osteoporosis and periodontal disease, but the direct effects of smoke-associated aryl hydrocarbons on bone are not well understood. Through the use of resveratrol (3,5,4'-trihydroxystilbene), a plant antifungal compound that we have recently demonstrated to be a pure AhR antagonist, we have investigated the effects of TCDD on osteogenesis. It was postulated that TCDD would inhibit osteogenesis in bone-forming cultures and that this inhibition would be antagonized by resveratrol. We employed the chicken periosteal osteogenesis (CPO) model, which has been shown to form bone in vitro in a pattern morphologically and biochemically similar to that seen in vivo, as well as a rat stromal cell bone nodule formation model. In the CPO model, alkaline phosphatase (AP) activity was reduced by up to 50% (P<0.01 vs control) in the presence of 10(-9) M TCDD and these effects were reversed by 10(-6) M resveratrol (P<0.05 vs TCDD alone). TCDD-mediated inhibition of osteogenesis was restricted primarily to the osteoblastic differentiation phase (days 0-2) as later addition did not appear to have any effects. Message levels for important bone-associated proteins (in the CPO model) such as collagen type I, osteopontin, bone sialoprotein and AP were inhibited by TCDD, an effect that was antagonized by resveratrol. Similar findings were obtained using the rat stromal bone cell line. TCDD (at concentrations as low as 10(-10)M) caused an approximately 33% reduction in AP activity, which was abrogated by 3. 5x10(-7) M resveratrol. TCDD also induced a marked reduction in mineralization ( approximately 75%) which was completely antagonized by resveratrol. These data suggest that AhR ligands inhibit osteogenesis probably through inhibition of osteodifferentiation and that this effect can be antagonized by resveratrol. Since high levels of AhR ligands are found in cigarette smoke, and further since smoking is an important risk factor in both osteoporosis and periodontal disease, it may be postulated that AhR ligands are the component of cigarette smoke linking smoking to osteoporosis and periodontal disease. If so, resveratrol could prove to be a promising preventive or therapeutic agent for smoking-related bone loss. PMID:11018766

Singh, S U; Casper, R F; Fritz, P C; Sukhu, B; Ganss, B; Girard, B; Savouret, J F; Tenenbaum, H C

2000-10-01

317

In vitro and in vivo studies of surface-structured implants for bone formation  

PubMed Central

Background and methods Micronanoscale topologies play an important role in implant osteointegration and determine the success of an implant. We investigated the effect of three different implant surface topologies on osteoblast response and bone regeneration. In this study, implants with nanotubes and micropores were used, and implants with flat surfaces were used as the control group. Results Our in vitro studies showed that the nanostructured topologies improved the proliferation, differentiation, and development of the osteoblastic phenotype. Histological analysis further revealed that the nanotopology increased cell aggregation at the implant-tissue interfaces and enhanced bone-forming ability. Pushout testing indicated that the nanostructured topology greatly increased the bone-implant interfacial strength within 4 weeks of implantation. Conclusion Nanotopography may improve regeneration of bone tissue and shows promise for dental implant applications. PMID:23028216

Xia, Lu; Feng, Bo; Wang, Peizhi; Ding, Siyang; Liu, Zhiyuan; Zhou, Jie; Yu, Rong

2012-01-01

318

Stability and Three-Dimensional Analysis of Bone Formation in Longitudinally Fluted Miniscrew Implants  

E-print Network

and potential failure of an orthodontic miniscrew. Conversely, a very high insertion placement torque places significant stresses on the surrounding bone leading to bone degradation or frictional necrosis.46 Another study places the validity of insertion... hardening by x-ray spectrum dispersion 2) photon starvation and poor signal to noise ratio 3) enhanced motion interference between the metal and adjacent structure caused by high contrast.60 Rebaudi et al in 2004 scanned a cylindrical biopsy...

Truong, An Van

2014-04-22

319

The effect of Lycii Radicis Cortex extract on bone formation in vitro and in vivo.  

PubMed

Osteoporosis is a common skeletal disease caused by decreased bone mass; it enhances the risk of bone fracture. This study aimed to discover novel herbal extract(s) for the treatment of osteoporosis. We screened 64 ethanol extracts of edible plants native to Korea for their ability to increase the cellular proliferation and differentiation of two osteoblastic cell lines: C3H10T1/2 and MC3T3-E1. We selected a Lycii Radicis Cortex (LRC), Lycium Chinese root bark as the primary candidate. Treatment with LRC extract showed enhanced alkaline phosphatase activity and increased expression of bone metabolic markers Alpl, Runx2, and Bglap genes in both osteoblastic cell lines. There was no effect on the osteoclastic differentiation of primary-cultured monocytes from the mouse bone marrows. Furthermore, the study examined the effect of LRC extract in vivo in ovariectomizd (OVX) mice for 8 weeks and 16 weeks, respectively. Bone mineral density (BMD) was significantly higher in LRC extract-administered group than in the non-LRC-administered OVX control group. The results indicated that LRC extract prevented the OVX-induced BMD loss in mice via promoting the differentiation of osteoblast linage cells. These results suggest that LRC extract may be a good natural herbal medicine candidate for the treatment of osteoporosis. PMID:25432011

Park, Eunkuk; Jin, Hyun-Seok; Cho, Doo-Yeoun; Kim, Jeonghyun; Kim, Mun-Chang; Choi, Chun Whan; Jin, Yilan; Lee, Ji-Won; Park, Jin-Hyok; Chung, Yoon-Sok; Huh, Dam; Jeong, Seon-Yong

2014-01-01

320

Bony defect repair in rabbit using hybrid rapid prototyping polylactic-co-glycolic acid/?-tricalciumphosphate collagen I/apatite scaffold and bone marrow mesenchymal stem cells  

PubMed Central

Background: In bone tissue engineering, extracellular matrix exerts critical influence on cellular interaction with porous biomaterial and the apatite playing an important role in the bonding process of biomaterial to bone tissue. The aim of this study was to observe the therapeutic effects of hybrid rapid prototyping (RP) scaffolds comprising polylactic-co-glycolic acid (PLGA), ?-tricalciumphosphate (?-TCP), collagen I and apatite (PLGA/?-TCP-collagen I/apatite) on segmental bone defects in conjunction with combination with bone marrow mesenchymal stem cells (BMSCs). Materials and Methods: BMSCs were seeded into the hybrid RP scaffolds to repair 15 mm defect in the radius of rabbits. Radiograph, microcomputed tomography and histology were used to evaluate new bone formation. Results: Radiographic analysis done from 12 to 36 weeks postoperative period demonstrated that new bone formed at the radial defect site and continues to increase until the medullary cavity is recanalized and remodelling is complete. The bone defect remained unconnected in the original RP scaffolds (PLGA/?-TCP) during the whole study. Histological observations conformed to the radiographic images. In hybrid RP scaffold group, woven bone united the radial defect at 12 weeks and consecutively remodeled into lamellar bone 24 weeks postoperation and finally matured into cortical bone with normal marrow cavity after another 12 weeks. No bone formation but connective tissue has been detected in RP scaffold at the same time. Conclusion: Collagen I/apatite sponge composite coating could improve new bone formation in vivo. The hybrid RP scaffold of PLGA/?-TCP skeleton with collagen I/apatite sponge composite coating is a promising candidate for bone tissue engineering. PMID:23960284

Pang, Long; Hao, Wei; Jiang, Ming; Huang, Jianguo; Yan, Yongnian; Hu, Yunyu

2013-01-01

321

Bone Sialoprotein  

Microsoft Academic Search

The search for a protein nucleator of hydroxyapatite crystal formation has been a focus for the isolation and characterization of the major non-collagenous proteins in bone. Of the proteins characterized to date, bone sialoprotein (BSP) has emerged as the only bona fide candidate for nucleation. BSP is a highly glycosylated and sulphated phosphoprotein that is found almost exclusively in mineralized

B. Ganss; R. H. Kim; J. Sodek

1999-01-01

322

Disorders of Bone Remodeling  

PubMed Central

The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skeleton must be maintained by constant bone modeling to carry out these crucial functions throughout life. Bone remodeling involves the removal of old or damaged bone by osteoclasts (bone resorption) and the subsequent replacement of new bone formed by osteoblasts (bone formation). Normal bone remodeling requires a tight coupling of bone resorption to bone formation to guarantee no alteration in bone mass or quality after each remodeling cycle. However, this important physiological process can be derailed by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and secondary diseases, which lead to the development of various bone disorders in both women and men. We review the major diseases of bone remodeling, emphasizing our current understanding of the underlying pathophysiological mechanisms. PMID:20936937

Feng, Xu; McDonald, Jay M.

2013-01-01

323

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)

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.

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

2002-01-01

324

Modulation of stromal cell-derived factor-1/CXC chemokine receptor 4 axis enhances rhBMP-2-induced ectopic bone formation.  

PubMed

Enhancement of in vivo mobilization and homing of endogenous mesenchymal stem cells (MSCs) to an injury site is an innovative strategy for improvement of bone tissue engineering and repair. The present study was designed to determine whether mobilization by AMD3100 and/or local homing by delivery of stromal cell-derived factor-1 (SDF-1) enhances recombinant human bone morphogenetic protein-2 (rhBMP-2) induced ectopic bone formation in an established rat model. Rats received an injection of either saline or AMD3100 treatment 1 h before harvesting of bone marrow for in vitro colony-forming unit-fibroblasts (CFU-F) culture or the in vivo subcutaneous implantation of absorbable collagen sponges (ACSs) loaded with saline, recombinant human bone morphogenetic protein-2 (rhBMP-2), SDF-1, or the combination of SDF-1 and rhBMP-2. AMD3100 treatment resulted in a significant decrease in CFU-F number, compared with saline, which confirmed that a single systemic AMD3100 treatment rapidly mobilized MSCs from the bone marrow. At 28 and 56 days, bone formation in the explanted ACS was assessed by microcomputed tomography (?CT) and histology. At 28 days, AMD3100 and/or SDF-1 had no statistically significant effect on bone volume (BV) or bone mineral content (BMC), but histology revealed more active bone formation with treatment of AMD3100, loading of SDF-1, or the combination of both AMD3100 and SDF-1, compared with saline-treated rhBMP-2 loaded ACS. At 56 days, the addition of AMD3100 treatment, loading of SDF-1, or the combination of both resulted in a statistically significant stimulatory effect on BV and BMC, compared with the saline-treated rhBMP-2 loaded ACS. Histology of the 56-day ACS were consistent with the ?CT analysis, exhibiting more mature and mineralized bone formation with AMD3100 treatment, SDF-1 loading, or the combination of both, compared with the saline-treated rhBMP-2 loaded ACS. The present study is the first that provides evidence of the efficacy of AMD3100 and SDF-1 treatment to stimulate trafficking of MSCs to an ectopic implant site, in order to ultimately enhance rhBMP-2 induced long-term bone formation. PMID:22035136

Wise, Joel K; Sumner, Dale Rick; Virdi, Amarjit S

2012-04-01

325

The effect of enamel matrix derivative (Emdogain) on bone formation: a systematic review  

Microsoft Academic Search

This systematic review focused on the question, if and to what extent enamel matrix derivative (Emdogain) [EMD]) promotes the regeneration of bone. The influence of combinations with other biomaterials was additionally evaluated. Twenty histomorphometric studies were included in this systematic review. Main results of the reviewed articles were (i) guide tissue regeneration (GTR) of infrabony defects seems to result in

Florian Rathe; Rüdiger Junker; Betsy M. Chesnutt; John A. Jansen

2009-01-01

326

Ectopic bone formation in severely combat-injured orthopedic patients -- a hematopoietic niche.  

PubMed

Combat-related heterotopic ossification (HO) has emerged as a common and problematic complication of modern wartime extremity injuries, contributing to substantial patient morbidity and loss of function. We have previously reported that HO-forming patients exhibit a more pronounced systemic and local inflammatory response very early in the wound healing process. Moreover, traumatized muscle-derived mesenchymal progenitor cells from these patients have a skewed differentiation potential toward bone. Here, we demonstrate that HO lesions excised from this patient population contain highly vascularized, mature, cancellous bone containing adipogenic marrow. Histologic analysis showed immature hematopoietic cells located within distinct foci in perivascular regions. The adipogenic marrow often contained low numbers of functional erythroid (BFU-E), myeloid (CFU-GM, CFU-M) and multilineage (CFU-GEMM) colony-forming hematopoietic progenitor cells (HPCs). Conversely, tissue from control muscle and non-HO traumatic wound granulation tissue showed no evidence of hematopoietic progenitor cell activity. In summary, our findings suggest that ectopic bone can provide an appropriate hematopoietic microenvironment for supporting the proliferation and differentiation of HPCs. This reactive and vibrant cell population may help maintain normal hematopoietic function, particularly in those with major extremity amputations who have sustained both massive blood loss, prompting systemic marrow stimulation, as well as loss of available native active marrow space. These findings begin to characterize the functional biology of ectopic bone and elucidate the interactions between HPC and non-hematopoietic cell types within the ectopic intramedullary hematopoietic microenvironmental niche identified. PMID:23727270

Davis, Thomas A; Lazdun, Yelena; Potter, Benjamin K; Forsberg, Jonathan A

2013-09-01

327

Talking among ourselves: paracrine control of bone formation within the osteoblast lineage.  

PubMed

While much research focuses on the range of signals detected by the osteoblast lineage that originate from endocrine influences, or from other cells within the body, there are also multiple interactions that occur within this family of cells. Osteoblasts exist as teams and form extensive communication networks both on, and within, the bone matrix. We provide four snapshots of communication pathways that exist within the osteoblast lineage between different stages of their differentiation, as follows: (1) PTHrP, a factor produced by early osteoblasts that stimulates the activity of more mature bone-forming cells and the most mature osteoblast embedded within the bone matrix, the osteocyte; (2) sclerostin, a secreted factor, released by osteocytes into their extensive communication network to restrict the activity of younger osteoblasts on the bone surface; (3) oncostatin M, a member of the IL-6/gp130 family of cytokines, expressed throughout osteoblast differentiation and acting to stimulate osteoblast activity that works on a different receptor in the mature osteocyte compared to the preosteoblast; and (4) Eph/ephrins, cell-contact-dependent kinases, and the osteoblast-lineage-specific interaction of EphB4 and ephrinB2, which provides a checkpoint for entry to the late stages of osteoblast differentiation and restricts RANKL expression. PMID:23695526

Tonna, Stephen; Sims, Natalie A

2014-01-01

328

Efficiency of High Molecular Weight Backbone Degradable HPMA Copolymer – Prostaglandin E1 Conjugate in Promotion of Bone Formation in Ovariectomized Rats  

PubMed Central

Multiblock, high molecular weight, linear, backbone degradable HPMA copolymer-prostaglandin E1 (PGE1) conjugate has been synthesized by RAFT polymerization mediated by a new bifunctional chain transfer agent (CTA), which contains an enzymatically degradable oligopeptide sequence flanked by two dithiobenzoate groups, followed by post-polymerization aminolysis and thiol-ene chain extension. The multiblock conjugate contains Asp8 as the bone-targeting moiety and enzymatically degradable bonds in the polymer backbone; in vivo degradation produces cleavage products that are below the renal threshold. Using an ovariectomized (OVX) rat model, the accumulation in bone and efficacy to promote bone formation was evaluated; low molecular weight conjugates served as control. The results indicated a higher accumulation in bone, greater enhancement of bone density, and higher plasma osteocalcin levels for the backbone degradable conjugate. PMID:23731780

Pan, Huaizhong; Sima, Monika; Miller, Scott C.; Kope?ková, Pavla; Yang, Jiyuan; Kope?ek, Jind?ich

2013-01-01

329

Glucosamine and chondroitin sulfate association increases tibial epiphyseal growth plate proliferation and bone formation in ovariectomized rats  

PubMed Central

OBJECTIVE: The growth plate consists of organized hyaline cartilage and serves as a scaffold for endochondral ossification, a process that mediates longitudinal bone growth. Based on evidence showing that the oral administration of glucosamine sulfate (GS) and/or chondroitin sulfate (CS) is clinically valuable for the treatment of compromised articular cartilage, the current study evaluated the effects of these molecules on the tibial epiphyseal growth plate in female rats. METHOD: The animals were divided into two control groups, including vehicle treatment for 45 days (GC45) and 60 days (GC60) and six ovariectomized (OVX) groups, including vehicle treatment for 45 days (GV45), GS for 45 days (GE45GS), GS+CS for 45 days (GE45GS+CS), vehicle for 60 days (GV60), GS for 60 days (GE60GS) and GS+CS for 60 days (GE60GS+CS). At the end of treatment, the tibias were dissected, decalcified and processed for paraffin embedding. Morphological and morphometric methods were employed for analyzing the distal tibial growth plates using picrosirius red staining and the samples were processed for histochemical hyaluronan detection. Morphometric analyses were performed using the 6.0ProPlus® Image system. RESULTS: Notably, after 60 days of treatment, the number of proliferative chondrocytes increased two-fold, the percentage of remaining cartilage increased four-fold and the percentage of trabecular bone increased three-fold in comparison to the control animals. CONCLUSION: GS and CS treatment drugs led to marked cellular proliferation of the growth plate and bone formation, showing that drug targeting of the tibial epiphyseal growth plate promoted longitudinal bone growth. PMID:25627998

Wolff, Roberta Bastos

2014-01-01

330

Parathyroid Hormone Stimulates TRANCE and Inhibits Osteoprotegerin Messenger Ribonucleic Acid Expression in Murine Bone Marrow Cultures: Correlation with Osteoclast-Like Cell Formation  

Microsoft Academic Search

We studied the effects of PTH on the expression of tumor necrosis factor-related activation-induced cytokine (TRANCE), osteoprote- gerin (OPG), and receptor activator of NF kB (RANK) messenger RNA (mRNA) in cultured murine bone marrow, calvaria, and osteoblasts. TRANCE, OPG, and RANK are recently identified regulators of os- teoclast formation. Bone marrow cells were cultured with or without PTH(1-34) for 6

SUN-KYEONG LEE; JOSEPH A. LORENZO

1999-01-01

331

Plumbagin attenuates cancer cell growth and osteoclast formation in the bone microenvironment of mice  

PubMed Central

Aim: To investigate the effects of plumbagin, a naphthoquinone derived from the medicinal plant Plumbago zeylanica, on human breast cancer cell growth and the cancer cell-induced osteolysis in the bone microenvironment of mice. Methods: Human breast cancer cell subline MDA-MB-231SA with the ability to spread and grow in the bone was tested. The cell proliferation was determined using the CCK-8 assay. Apoptosis was detected with Annexin V/PI double-labeled flow cytometry. Red fluorescent protein-labeled MDA-MB-231SArfp cells were injected into the right tibia of female BALB/c-nu/nu mice. Three days after the inoculation, the mice were injected with plumbagin (2, 4, or 6 mg/kg, ip) 5 times per week for 7 weeks. The growth of the tumor cells was monitored using an in vivo imaging system. After the mice were sacrificed, the hind limbs were removed for radiographic and histological analyses. Results: Plumbagin (2.5–20 ?mol/L) concentration-dependently inhibited the cell viability and induced apoptosis of MDA-MB-231SA cells in vitro (the IC50 value of inhibition of cell viability was 14.7 ?mol/L). Administration of plumbagin to breast cancer bearing mice delayed the tumor growth by 2–3 weeks and reduced the tumor volume by 44%–74%. The in vivo imaging study showed that plumbagin dose-dependently inhibited MDA-MB-231SArfp cell growth in bone microenvironment. Furthermore, X-ray images and micro-CT study demonstrated that plumbagin reduced bone erosion area and prevented a decrease in bone tissue volume. Histological studies showed that plumbagin dose-dependently inhibited the breast cancer cell growth, enhanced the cell apoptosis and reduced the number of TRAcP-positive osteoclasts. Conclusion: Plumbagin inhibits the cell growth and induces apoptosis in human breast cancer cells in mice bone microenvironment, leading to significant reduction in osteolytic lesions caused by the tumor cells. PMID:24384612

Yan, Wei; Wang, Ting-yu; Fan, Qi-ming; Du, Lin; Xu, Jia-ke; Zhai, Zan-jing; Li, Hao-wei; Tang, Ting-ting

2014-01-01

332

Accelerated bone formation and increased osteoblast number contribute to the abnormal tooth germ development in parathyroid hormone-related protein knockout mice.  

PubMed

Our previous study showed that tooth germs at late embryonic stage [later than embryonic day 17.5 (E17.5)] and neonatal homozygous parathyroid hormone-related protein (PTHrP)-knockout mice are compressed or penetrated by the surrounding alveolar bone tissue. In vivo and in vitro studies have shown that the development of the tooth germ proper is not disturbed, but insufficient alveolar bone resorption, due to the decreased number and hypofunction of osteoclasts, is the main cause of this abnormality. In addition to the insufficient alveolar bone resorption, progressive bone formation toward tooth germs was observed in homozygous mice, suggesting that accelerated bone formation also contributes to this abnormality. To further investigate this, homozygous mice at E14.0 and E15.5, when alveolar bone is forming, were used for histochemical and bone histomorphometric analyses. In contrast to the late embryonic stage, the alveolar bone did not yet compress developing tooth germs in homozygous mice on E14.0, but a larger amount of bone tissue was seen compared to wild-type littermates. Histomorphometric analysis of bone at E14.0 revealed that the osteoblast numbers and surfaces in the mandibles and in the bone collar of femora of homozygous mice were significantly higher than those of wild-type mice. However, unlike our previous study showing the osteoclast surface on E18.5 in homozygous mice to be significantly lower than that of wild-type mice, this study at E14.0 showed no significant difference between the two genotypes. To evaluate the amount of calcification around tooth germs, 3D images of mandibles were reconstructed from the calcein-labeled sections of the wild-type and mutant mice. Labeling was performed at E14.0, and the mice were sacrificed 1 h after the calcein injection to minimize the effect of bone resorption. Comparison of the 3D images revealed that the labeled surface was larger around developing tooth germs in homozygous mouse than in wild-type mouse. On day E15.5, osteoblasts approached the enamel organ of homozygous mice but this was not observed in wild-type mice. In this study, we report a systemic increase in osteoblast number and accelerated bone formation in homozygous PTHrP-knockout mice, both of which contribute to the abnormal tooth development. PMID:15542035

Kitahara, Y; Suda, N; Terashima, T; Baba, O; Mekaapiruk, K; Hammond, V E; Takano, Y; Ohyama, K

2004-11-01

333

BMP-Non-Responsive Sca1+CD73+CD44+ Mouse Bone Marrow Derived Osteoprogenitor Cells Respond to Combination of VEGF and BMP-6 to Display Enhanced Osteoblastic Differentiation and Ectopic Bone Formation  

PubMed Central

Clinical trials on fracture repair have challenged the effectiveness of bone morphogenetic proteins (BMPs) but suggest that delivery of mesenchymal stem cells (MSCs) might be beneficial. It has also been reported that BMPs could not increase mineralization in several MSCs populations, which adds ambiguity to the use of BMPs. However, an exogenous supply of MSCs combined with vascular endothelial growth factor (VEGF) and BMPs is reported to synergistically enhance fracture repair in animal models. To elucidate the mechanism of this synergy, we investigated the osteoblastic differentiation of cloned mouse bone marrow derived MSCs (D1 cells) in vitro in response to human recombinant proteins of VEGF, BMPs (-2, -4, -6, -9) and the combination of VEGF with BMP-6 (most potent BMP). We further investigated ectopic bone formation induced by MSCs pre-conditioned with VEGF, BMP-6 or both. No significant increase in mineralization, phosphorylation of Smads 1/5/8 and expression of the ALP, COL1A1 and osterix genes was observed upon addition of VEGF or BMPs alone to the cells in culture. The lack of CD105, Alk1 and Alk6 expression in D1 cells correlated with poor response to BMPs indicating that a greater care in the selection of MSCs is necessary. Interestingly, the combination of VEGF and BMP-6 significantly increased the expression of ALP, COL1A1 and osterix genes and D1 cells pre-conditioned with VEGF and BMP-6 induced greater bone formation in vivo than the non-conditioned control cells or the cells pre-conditioned with either VEGF or BMP-6 alone. This enhanced bone formation by MSCs correlated with higher CADM1 expression and OPG/RANKL ratio in the implants. Thus, combined action of VEGF and BMP on MSCs enhances osteoblastic differentiation of MSCs and increases their bone forming ability, which cannot be achieved through use of BMPs alone. This strategy can be effectively used for bone repair. PMID:25048464

Madhu, Vedavathi; Li, Ching-Ju; Dighe, Abhijit S.; Balian, Gary; Cui, Quanjun

2014-01-01

334

A plant virus substrate induces early upregulation of BMP2 for rapid bone formation.  

PubMed

Many nanoscale materials have been developed to investigate the effects on stem cell differentiations via topographical and chemical cues for applications in tissue engineering and regenerative medicine. The use of plant viruses as cell supporting substrates has been of particular interest due to the rapid induction of bone marrow derived mesenchymal stem cells (BMSCs) towards osteogenic cells. In this study, the role of Tobacco mosaic virus (TMV) and its early effects on osteoinduction with particular emphasis on the regulation of bone morphogenetic protein-2 (BMP2) was examined. We observed that the cells on the virus substrate immediately aggregated and formed bone-like nodules within 24 hours. An immediate increase in BMP2 gene and protein expression for cells on the TMV substrate was observed within 8 hours of osteoinduction. Moreover, BMP2 expression was highly localized to cells within the cell aggregates. This enhanced differentiation only occurred when TMV was coated on a solid support but not upon adding the virus to the media solution. Taken together, the results from this study highlight the potential of virus-based nanomaterials to promote endogenous BMP2 production which may prove to be a unique approach to studying the regulatory mechanisms involved in early osteoblastic differentiation. PMID:22532088

Sitasuwan, Pongkwan; Lee, L Andrew; Bo, Peng; Davis, Erin N; Lin, Yuan; Wang, Qian

2012-06-01

335

Multi-Lamellar Structures in Nafion  

NASA Astrophysics Data System (ADS)

Both proton conductivity and gas diffusion are key factors in the performance of a fuel cell proton exchange membrane, PEM. They are critically dependent on water content and morphology, especially in the three phase region where catalyst, PEM, and gases such as fuel or oxidizer co-exist. Here we show that lamellar structures composed of thin alternating water rich and Nafion rich layers exist at the interface between SiO2 and the hydrated Nafion film. Lamellae thickness and number of layers increase with humidity. Some lamellae remained in the film after dehydration. Multilayer lamellae are not observed for Nafion on Au or Pt surfaces. Instead, a thin partially hydrated single interfacial layer occurs and decreases in thickness to a few angstroms as humidity is reduced to zero. The absorption isotherm of the rest of the Nafion film is similar to that of bulk Nafion for all three surfaces investigated.

Dura, Joseph A.; Murthi, Vivek S.; Hartman, Michael R.; Satija, Sushil K.; Majkrzak, Charles F.

2009-03-01

336

Alternaria keratitis after deep anterior lamellar keratoplasty.  

PubMed

To describe a case of Alternaria keratitis in a 30-year-old male patient who presented with bilateral vascularised central corneal opacity and underwent deep anterior lamellar keratoplasty (DALK) in the left eye. Patient was treated for recurrent epithelial defect with a bandage contact lens in the follow-up visits after DALK. Subsequently, patient presented with pigmented fungal keratitis, which on culture examination of the corneal scrapping demonstrated Alternaria species. Patient had to undergo a repeat DALK as the keratitis did not resolve with medical therapy alone. Patient did not have a recurrence for 11 months following the regraft. This case report highlights the importance of considering the Alternaria species as a possibile cause of non-resolving fungal keratitis after DALK. PMID:24669155

Naik, Mekhla; Mohd Shahbaaz; Sheth, Jay; Sunderamoorthy, S K

2014-01-01

337

Alternaria Keratitis after Deep Anterior Lamellar Keratoplasty  

PubMed Central

To describe a case of Alternaria keratitis in a 30-year-old male patient who presented with bilateral vascularised central corneal opacity and underwent deep anterior lamellar keratoplasty (DALK) in the left eye. Patient was treated for recurrent epithelial defect with a bandage contact lens in the follow-up visits after DALK. Subsequently, patient presented with pigmented fungal keratitis, which on culture examination of the corneal scrapping demonstrated Alternaria species. Patient had to undergo a repeat DALK as the keratitis did not resolve with medical therapy alone. Patient did not have a recurrence for 11 months following the regraft. This case report highlights the importance of considering the Alternaria species as a possibile cause of non-resolving fungal keratitis after DALK. PMID:24669155

Naik, Mekhla; Mohd. Shahbaaz; Sheth, Jay; Sunderamoorthy, S. K.

2014-01-01

338

Primary intraosseous hybrid nerve sheath tumor of femur: A hitherto undescribed occurrence in bone with secondary aneurysmal bone cyst formation resulting in pathological fracture.  

PubMed

Soft tissue perineurioma besides its pure form may coexist with schwannoma as hybrid nerve sheath tumor (HNST) which occurs in the limbs, head and neck, trunk and occasionally colon but origination in other organ sites has not been reported. We report the first case of primary intraosseous HNST. An 18-year-old man suffered from pathological fracture of his right femur after an impact which was preceded by a similar episode two weeks previously. Plain radiograph revealed a displaced fracture in the superior diaphysis of the right femur where an expansile osteolytic lesion with relatively well defined borders was seen. Histologic examination of the curetted lesion showed a well circumscribed spindle cell neoplasm displaying predominantly storiform but focally whorled patterns. In areas, the cells possessed thin wavy spindle nuclei and delicate elongated bipolar cytoplasmic processes supported in a fibromyxoid stroma. They stained positively for EMA, claudin, CD34, collagen 4 and focally for S100 but negatively for MUC4 and BCL-2, indicative of perineurial differentiation. Situated in the periphery of some of these perineurial whorls are spindle cells bearing plump tapering wavy nuclei and palely eosinophilic cytoplasm with indistinct cell borders. They stained intensely for S100 but negatively for EMA, claudin, CD34, collagen 4, MUC4 and BCL-2, consistent with schwannian differentiation. Focally, these two varieties of cells intimately intermingled with each other. Features of aneurysmal bone cyst (ABC) formation were present but no mitotic figures, establishing the final diagnosis of primary intraosseous HNST with secondary ABC formation. The patient remained well 7 months after curettage and internal fixation of his fracture. PMID:25466465

Chow, Louis Tsun Cheung

2014-11-14

339

ERR? Is Not Required for Skeletal Development but Is a RUNX2-Dependent Negative Regulator of Postnatal Bone Formation in Male Mice  

PubMed Central

To assess the effects of the orphan nuclear Estrogen receptor-related receptor gamma (ERR?) deficiency on skeletal development and bone turnover, we utilized an ERR? global knockout mouse line. While we observed no gross morphological anomalies or difference in skeletal length in newborn mice, by 8 weeks of age ERR? +/? males but not females exhibited increased trabecular bone, which was further increased by 14 weeks. The increase in trabecular bone was due to an increase in active osteoblasts on the bone surface, without detectable alterations in osteoclast number or activity. Consistent with the histomorphometric results, we observed an increase in gene expression of the bone formation markers alkaline phosphatase (Alp) and bone sialoprotein (Bsp) in bone and increase in serum ALP, but no change in the osteoclast regulators receptor activator of NF-?B ligand (RANKL) and osteoprotegerin (OPG) or the resorption marker carboxy-terminal collagen crosslinks (CTX). More colony forming units-alkaline phosphatase and -osteoblast (CFU-ALP, CFU-O respectively) but not CFU-fibroblast (CFU-F) formed in ERR? +/? versus ERR? +/+ stromal cell cultures, suggesting that ERR? negatively regulates osteoblast differentiation and matrix mineralization but not mesenchymal precursor number. By co-immunoprecipitation experiments, we found that ERR? and RUNX2 interact in an ERR? DNA binding domain (DBD)-dependent manner. Treatment of post-confluent differentiating bone marrow stromal cell cultures with Runx2 antisense oligonucleotides resulted in a reduction of CFU-ALP/CFU-O in ERR? +/? but not ERR? +/+ mice compared to their corresponding sense controls. Our data indicate that ERR? is not required for skeletal development but is a sex-dependent negative regulator of postnatal bone formation, acting in a RUNX2- and apparently differentiation stage-dependent manner. PMID:25313644

Cardelli, Marco; Aubin, Jane E.

2014-01-01

340

Inhibition of GSK-3? Rescues the Impairments in Bone Formation and Mechanical Properties Associated with Fracture Healing in Osteoblast Selective Connexin 43 Deficient Mice  

PubMed Central

Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated ?-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/ Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, ?-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3?, a key component of the ?-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3? activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating ?-catenin expression and thus bone formation during fracture repair. PMID:24260576

Loiselle, Alayna E.; Lloyd, Shane A. J.; Paul, Emmanuel M.; Lewis, Gregory S.; Donahue, Henry J.

2013-01-01

341

Runx2-I Isoform Contributes to Fetal Bone Formation Even in the Absence of Specific N-Terminal Amino Acids  

PubMed Central

The Runt-related transcription factor 2 (Runx2) gene encodes the transcription factor Runx2, which is the master regulator of osteoblast development; insufficiency of this protein causes disorders of bone development such as cleidocranial dysplasia. Runx2 has two isoforms, Runx2-II and Runx2-I, and production of each isoform is controlled by a unique promoter: a distal promoter (P1) and a proximal promoter (P2), respectively. Although several studies have focused on differences and similarities between the two Runx2 isoforms, their individual roles in bone formation have not yet been determined conclusively, partly because a Runx2-I-targeted mouse model is not available. In this study, we established a novel Runx2-manipulated mouse model in which the first ATG of Runx2-I was replaced with TGA (a stop codon), and a neomycin-resistant gene (neo) cassette was inserted at the first intron of Runx2-I. Homozygous Runx2-Ineo/neo mice showed severely reduced expression of Runx2-I, whereas Runx2-II expression was largely retained. Runx2-Ineo/neo mice showed neonatal lethality, and in these mice, intramembranous ossification was more severely defective than endochondral ossification, presumably because of the greater involvement of Runx2-I, compared with that of Runx2-II in intramembranous ossification. Interestingly, the depletion of neo rescued the above-described phenotypes, indicating that the isoform-specific N-terminal region of Runx2-I is not functionally essential for bone development. Taken together, our results provide a novel clue leading to a better understanding of the roles of Runx2 isoforms in osteoblast development. PMID:25244033

Okura, Hideaki; Sato, Shintaro; Kishikawa, Sari; Kaneto, Satoshi; Nakashima, Tomoki; Yoshida, Nobuaki; Takayanagi, Hiroshi; Kiyono, Hiroshi

2014-01-01

342

[Vitamin K metabolism. Menaquinone-4 (MK-4) formation from ingested VK analogues and its potent relation to bone function].  

PubMed

Phylloquinone (vitamin K(1) = VK(1)) and the menaquinones (MK-n, or vitamin K(2) = VK(2)) are naturally occurring forms of VK. Most of the menaquinone series are synthesized by microorganisms, but we have reported that MK-4 is usual in being synthesized by the conversion of orally ingested VK(1) or MK-n in the major tissues of germfree rats and mice which lack their intestinal microflora. This result led us to deny 1960's Martius' hypothesis that described the participation of bacterial enzyme of the intestinal flora to this conversion. VK acts as a cofactor in the posttranslational synthesis of gamma-carboxyglutamic acid (Gla) from glutamic acid (Glu) residues in the nascent Gla-protein molecule. Therefore, VK is essential for blood coagulation (various clotting factors) and bone structure (as osteocalcin [OC = BGP] and matrix Gla-protein [MGP] in mammals. In addition to the liver, VK is found in the bone, brain, heart, testis, kidney, pancreas and salivary glands mainly as MK-4, and it has been reported that MK-4 itself has specific biological activities in these tissues beside Gla-protein formation. However, the physiological role of MK-4 in these organs has not been fully understood yet. Recently MK-4 has been attracted the attention of researchers due to its activities such as apoptotic activity on the osteoclast cells and leukemia cells, SXR/PXR ligand, and so on. We further review the potent important physiological role of MK-4 in the bone as well as other major tissues. PMID:17982185

Komai, Michio; Shirakawa, Hitoshi

2007-11-01

343

Bone formation after damaging in vivo fatigue loading results in recovery of whole-bone monotonic strength and increased fatigue life.  

PubMed

Bone has a remarkable capacity for self-repair. We previously reported a woven bone response after damaging in vivo fatigue loading of the rat ulna that led to a rapid recovery of whole-bone strength. In the current study we asked: does the bone response in the 12 days after damaging fatigue loading result in a bone that has normal fatigue properties? The right forelimbs of 52 adult rats were subjected to a single bout of in vivo fatigue loading. Nonloaded left forelimbs were used as controls. Ulnar geometric properties were assessed by peripheral quantitative computed tomography (pQCT) and ex vivo mechanical properties were assessed by three-point bending. On day 0, ulnae from loaded forelimbs had a 15-20% reduction in stiffness and ultimate force versus controls (p < 0.10), indicative of structural damage. On day 12, bone area at the midshaft was increased by 27% (p < 0.001) and microCT scans revealed periosteal woven bone at this site. This bone response led to a recovery of the monotonic properties of loaded ulnae at day 12 versus control (stiffness, p = 0.73; ultimate force, p = 0.96). Importantly, fatigue testing ex vivo at day 12 demonstrated significantly greater fatigue life in in vivo loaded ulnae versus controls (p < 0.001). Additionally, the slope of the fatigue-life curve was significantly less in loaded versus control ulnae (p < 0.002). We conclude that woven bone "repair" of a bone damaged by fatigue loading restores whole-bone strength and enhances resistance to further damage by repetitive loading. PMID:17106875

Silva, Matthew J; Touhey, Daniel C

2007-02-01

344

Effects of Cell-Attachment and Extracellular Matrix on Bone Formation In Vivo in Collagen-Hydroxyapatite Scaffolds  

PubMed Central

Cell-based tissue engineering can be used to replace missing or damaged bone, but the optimal methods for delivering therapeutic cells to a bony defect have not yet been established. Using transgenic reporter cells as a donor source, two different collagen-hydroxyapatite (HA) scaffolds, and a critical-size calvarial defect model, we investigated the effect of a cell-attachment period prior to implantation, with or without an extracellular matrix-based seeding suspension, on cell engraftment and osteogenesis. When quantitatively compared, the in-house scaffold implanted immediately had a higher mean radiopacity than in-house scaffolds incubated overnight. Both scaffold types implanted immediately had significantly higher area fractions of donor cells, while the in-house collagen-HA scaffolds implanted immediately had higher area fractions of the mineralization label compared with groups incubated overnight. When the cell loading was compared in vitro for each delivery method using the in-house scaffold, immediate loading led to higher numbers of delivered cells. Immediate loading may be preferable in order to ensure robust bone formation in vivo. The use of a secondary ECM carrier improved the distribution of donor cells only when a pre-attachment period was applied. These results have improved our understanding of cell delivery to bony defects in the context of in vivo outcomes. PMID:25329879

Villa, Max M.; Wang, Liping; Rowe, David W.; Wei, Mei

2014-01-01

345

Polarized light microscopic analysis of bone formation after inhibition of cyclooxygenase 1 and 2.  

PubMed

Potassium diclofenac is a potent nonsteroidal anti-inflammatory drug (NSAID) and COX isoforms (COX-1 and COX-2) inhibitor. Quantitative analysis of birefringence with polarized light microscopy is a useful method to investigate the macromolecular orientation and organization of collagen fibers in connective tissues. The aim of this research was to analyze the collagen structure and maturation in bone formed after potassium diclofenac administration, during first molar orthodontic movement. Sixty Wistar rats were divided in two equal groups (N = 30): control (C) and potassium diclofenac (PD). The animals in Group C received 0.9% saline solution and the PD group received potassium diclofenac Cataflam (5 mg/kg). Animals were sacrificed 3, 7, or 14 days after a NiTi unilateral closed-coil spring was stretched between the upper right first molar and the incisors. The first molar area was fixed, decalcified, and histologically processed using picrosirius pigment. The collagen birefringence of bone turnover was analyzed by phase retardation. Two-way ANOVA and Tukey's test showed that optical retardation was influenced by time and treatment. There was increase in the collagen organization over time. On the third day, the C group showed better collagen organization than the PD group. Potassium diclofenac interfered in collagen maturation, reducing fibril organization in the initial phase of orthodontic movement. PMID:19937640

Retamoso, Luciana Borges; Montagner, Francisco; Camargo, Elisa Souza; Vitral, Roberto Willer Farinazzo; Tanaka, Orlando Motohiro

2010-02-01

346

Probable Ankylosaur Ossicles from the Middle Cenomanian Dunvegan Formation of Northwestern Alberta, Canada  

PubMed Central

A sample of six probable fragmentary ankylosaur ossicles, collected from Cenomanian deposits of the Dunvegan Formation along the Peace River, represent one of the first dinosaurian skeletal fossils reported from pre-Santonian deposits in Alberta. Specimens were identified as ankylosaur by means of a palaeohistological analysis. The primary tissue is composed of zonal interwoven structural fibre bundles with irregularly-shaped lacunae, unlike the elongate lacunae of the secondary lamellar bone. The locality represents the most northerly Cenomanian occurrence of ankylosaur skeletal remains. Further fieldwork in under-examined areas of the province carries potential for additional finds. PMID:24816807

Burns, Michael E.; Vavrek, Matthew J.

2014-01-01

347

Swelling and shrinking kinetics of a lamellar gel phase   

E-print Network

We investigate the swelling and shrinking of L-beta lamellar gel phases composed of surfactant and fatty alcohol after contact with aqueous poly(ethyleneglycol) solutions. The height change Delta h(t) is diffusionlike with ...

Egelhaaf, Stefan U; Baker, M.E.; Shaw, N.; Fairhurst, David John

2008-05-01

348

Solcoseryl, a tissue respiration stimulating agent, significantly enhances the effect of capacitively coupled electric field on the promotion of bone formation around dental implants.  

PubMed

In the present study we examined the combined effect of application of a capacitively coupled electric field (CCEF) and the tissue respiration stimulating agent, Solcoseryl, on the promotion of bone formation around dental implants histologically and mechanically. After a dental implant was inserted into each femur of Japanese white rabbits, Solcoseryl (2 ml/kg) was administered intravenously in the ear vein and a CCEF was applied for 4 h per day for 14 days. The degree of bone formation on microscopic observation, bone contact ratio, bone surface area ratio, and the level of removal torque of the implant in the Solcoseryl- and CCEF-treated group were significantly higher than the respective value in the control group, which had not been treated with Solcoseryl nor CCEF. Thus, the combination of CCEF stimulation and Solcoseryl effectively promoted the formation of new bone. It is suggested that the clinical use of a combination of CCEF stimulation and Solcoseryl for dental implants promotes osseointegration. PMID:12755779

Ochi, Morio; Wang, Pao-Li; Ohura, Kiyoshi; Takashima, Shigenori; Kagami, Hiroyuki; Hirose, Yukito; Kaku, Tohru; Sakaguchi, Kunihiko

2003-06-01

349

Linkage of autosomal recessive lamellar ichthyosis to chromosome 14q  

SciTech Connect

The authors have mapped the locus for lamellar ichthyosis (LI), an autosomal recessive skin disease characterized by abnormal cornification of the epidermis. Analysis using both inbred and outbred families manifesting severe LI showed complete linkage to several markers within a 9.3-cM region on chromosome 14q11. Affected individuals in inbred families were also found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. Several transcribed genes have been mapped to the chromosome 14 region containing the LI gene. The transglutaminase 1 gene (TGM1), which encodes one of the enzymes responsible for cross-linking epidermal proteins during formation of the stratum corneum, maps to this interval. The TGM1 locus was completely linked to LI (Z = 9.11), suggesting that TGM1 is a good candidate for further investigation of this disorder. The genes for four serine proteases also map to this region but are expressed only in hematopoietic or mast cells, making them less likely candidates.

Russell, L.J.; Compton, J.G.; Bale, S.J. [National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD (United States); DiGiovanna, J.J. [National Cancer Institute, Bethesda, MD (United States); Hashem, N. [Ains-Shams Univ. Medical Genetics Center, Cairo (Egypt)

1994-12-01

350

Negative pressure technology enhances bone regeneration in rabbit skull defects  

PubMed Central

Background Bone is a slowly regenerating tissue influenced by various physiological processes, including proliferation, differentiation, and angiogenesis, under the control of growth factors. Shortening this healing time is an important and popular clinical research focus in orthopedics. Negative pressure can stimulate angiogenesis, improve blood circulation, promote granulation tissue growth and accelerate tissue wound healing. We sought to determine whether negative pressure could reduce bone healing time in a rabbit cranial defect model. Methods Four symmetrical holes (diameter, 3.5?mm) were drilled into the skulls of 42 New Zealand white rabbits, with two holes in each parietal bone. For each rabbit, the two sides were then randomly assigned into experimental and control groups. Using negative pressure suction tubes, experimental holes were treated with ?50 kPa for 15?minutes, four times per day, whereas the control holes remained untreated. After 4?weeks, the negative pressure suction tubes were removed. At 2, 4, 6 and 8?weeks, three-dimensional (3D) reconstruction computed tomography (CT), X-ray radiopacity, and two-photon absorptiometry were used to evaluate new bone formation. Histological changes were determined by hematoxylin and eosin (H.E) staining. At weekly intervals until 6?weeks, the mRNA expression levels of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2 were evaluated by RT-PCR. A paired student’s t-test was employed to compare X-ray radiopacity and bone density measurements between the experimental and control groups. Results 3D-reconstruction CT showed that new bone regeneration in the experimental group was greater than that in the control group at 4 and 6?weeks. At these time points, the experimental group presented with higher X-ray radiopacity and increased bone density (P?bone were observed by H.E staining at 2?weeks in the experimental group. By 6?weeks, the new bone had matured into lamellar bone in the experimental group. RT-PCR results showed that VEGF and BMP-2 were highly expressed in the experimental group as compared with control. Conclusions Intermittent negative pressure can promote the regeneration of bone possibly by enhancing the expression of VEGF and BMP-2. PMID:23452626

2013-01-01

351

ERK1 and ERK2 regulate chondrocyte terminal differentiation during endochondral bone formation.  

PubMed

Chondrocytes in the epiphyseal cartilage undergo terminal differentiation prior to their removal through apoptosis. To examine the role of ERK1 and ERK2 in chondrocyte terminal differentiation, we generated Osx-Cre; ERK1(-/-) ; ERK2(flox/flox) mice (cKOosx ), in which ERK1 and ERK2 were deleted in hypertrophic chondrocytes. These cKOosx mice were grossly normal in size at birth, but by 3 weeks of age exhibited shorter long bones. Histological analysis in these mice revealed that the zone of hypertrophic chondrocytes in the growth plate was markedly expanded. In situ hybridization and quantitative real-time PCR analyses demonstrated that Mmp13 and Osteopontin expression was significantly decreased, indicating impaired chondrocyte terminal differentiation. Moreover, Egr1 and Egr2, transcription factors whose expression is restricted to the last layers of hypertrophic chondrocytes in wild type mice, were also strongly downregulated in these cKOosx mice. In transient transfection experiments in the RCS rat chondrosarcoma cell line, the expression of Egr1, Egr2, or a constitutively active mutant of MEK1 increased the activity of an Osteopontin promoter, while the MEK1-induced activation of the Osteopontin promoter was inhibited by the co-expression of Nab2, an Egr1 and Egr2 co-repressor. These results suggest that MEK1-ERK signaling activates the Osteopontin promoter in part through Egr1 and Egr2. Finally, our histological analysis of cKOosx mice demonstrated enchondroma-like lesions in the bone marrow that are reminiscent of human metachondromatosis, a skeletal disorder caused by mutations in PTPN11. Our observations suggest that the development of enchondromas in metachondromatosis may be caused by reduced ERK MAPK signaling. This article is protected by copyright. All rights reserved. PMID:25401279

Chen, Zhijun; Yue, Susan X; Zhou, Guang; Greenfield, Edward M; Murakami, Shunichi

2014-11-17

352

Alterations in phosphorus, calcium and PTHrP contribute to defects in dental and dental alveolar bone formation in calcium-sensing receptor-deficient mice.  

PubMed

To determine whether the calcium-sensing receptor (CaR) participates in tooth formation and dental alveolar bone development in mandibles in vivo, we examined these processes, as well as mineralization, in 2-week-old CaR-knockout (CaR(-/-)) mice. We also attempted to rescue the phenotype of CaR(-/-) mice by genetic means, in mice doubly homozygous for CaR and 25-hydroxyvitamin D 1alpha-hydroxylase [1alpha(OH)ase] or parathyroid hormone (Pth). In CaR(-/-) mice, which exhibited hypercalcemia, hypophosphatemia and increased serum PTH, the volumes of teeth and of dental alveolar bone were decreased dramatically, whereas the ratio of the area of predentin to total dentin and the number and surface of osteoblasts in dental alveolar bone were increased significantly, as compared with wild-type littermates. The normocalcemia present in CaR(-/-);1alpha(OH)ase(-/-) mice only slightly improved the defects in dental and alveolar bone formation observed in the hypercalcemic CaR(-/-) mice. However, these defects were completely rescued by the additional elimination of hypophosphatemia and by an increase in parathyroid hormone-related protein (PTHrP) expression in the apical pulp, Hertwig's epithelial root sheath and mandibular tissue in CaR(-/-); Pth(-/-) mice. Therefore, alterations in calcium, phosphorus and PTHrP contribute to defects in the formation of teeth and alveolar bone in CaR-deficient mice. This study indicates that CaR participates in the formation of teeth and in the development of dental alveolar bone in mandibles in vivo, although it appears to do so largely indirectly. PMID:20150282

Sun, Wen; Sun, Weiwei; Liu, Jingning; Zhou, Xichao; Xiao, Yongjun; Karaplis, Andrew; Pollak, Martin R; Brown, Edward; Goltzman, David; Miao, Dengshun

2010-03-01

353

[A comparative evaluation of bone tissue formation by tissue scaffold and osteoplastic material «Bio-Oss» transplantation in the maxillary sinus floor].  

PubMed

The effectiveness of bone tissue formation by transplantation of tissue-engineering scaffold and frequently used osteoplastic material «Bio-Oss» combined construction in maxillary sinus floor was evaluated and marked differences in regeneration terms by this treatment mode were found out. PMID:23268217

Alekseeva, I S; Rachinskaia, O A; Volkov, A V; Kulakov, A A; Gol'dshte?n, D V

2012-01-01

354

Fluid pressure gradients, arising from oscillations in intramedullary pressure, is correlated with the formation of bone and inhibition of intracortical porosity.  

PubMed

Fluid flow that arises from the functional loading of bone tissue has been proposed to be a critical regulator of skeletal mass and morphology. To test this hypothesis, the bone adaptive response to a physiological fluid stimulus, driven by low magnitude, high frequency oscillations of intramedullary pressure (ImP), were examined, in which fluid pressures were achieved without deforming the bone tissue. The ulnae of adult turkeys were functionally isolated via transverse epiphyseal osteotomies, and the adaptive response to four weeks of disuse (n=5) was compared to disuse plus 10 min per day of a physiological sinusoidal fluid pressure signal (60 mmHg, 20Hz). Disuse alone resulted in significant bone loss (5.7+/-1.9%, p< or =0.05), achieved by thinning the cortex via endosteal resorption and an increase in intracortical porosity. By also subjecting bone to oscillatory fluid flow, a significant increase in bone mass at the mid-diaphysis (18.3+/-7.6%, p<0.05), was achieved by both periosteal and endosteal new bone formation. The spatial distribution of the transcortical fluid pressure gradients (inverted Delta P(r)), a parameter closely related to fluid velocity and fluid shear stress, was quantified in 12 equal sectors across a section at the mid-diaphyses. A strong correlation was found between the inverted Delta P(r) and total new bone formation (r=0.75, p=0.01); and an inverse correlation (r=-0.75, p=0.01) observed between inverted Delta P(r) and the area of increased intracortical porosity, indicating that fluid flow signals were necessary to maintain bone mass and/or inhibit bone loss against the challenge of disuse. By generating this fluid flow in the absence of matrix strain, these data suggest that anabolic fluid movement plays a regulatory role in the modeling and remodeling process. While ImP increases uniformly in the marrow cavity, the distinct parameters of fluid flow vary substantially due to the geometry and ultrastructure of bone, which ultimately defines the spatial non-uniformity of the adaptive process. PMID:14499292

Qin, Yi Xian; Kaplan, Tamara; Saldanha, Anita; Rubin, Clinton

2003-10-01

355

Oxytocin and bone.  

PubMed

One of the most meaningful results recently achieved in bone research has been to reveal that the pituitary hormones have profound effect on bone, so that the pituitary-bone axis has become one of the major topics in skeletal physiology. Here, we discuss the relevant evidence about the posterior pituitary hormone oxytocin (OT), previously thought to exclusively regulate parturition and breastfeeding, which has recently been established to directly regulate bone mass. Both osteoblasts and osteoclasts express OT receptors (OTR), whose stimulation enhances bone mass. Consistent with this, mice deficient in OT or OTR display profoundly impaired bone formation. In contrast, bone resorption remains unaffected in OT deficiency because, even while OT stimulates the genesis of osteoclasts, it inhibits their resorptive function. Furthermore, in addition to its origin from the pituitary, OT is also produced by bone marrow osteoblasts acting as paracrine-autocrine regulator of bone formation modulated by estrogens. In turn, the power of estrogen to increase bone mass is OTR-dependent. Therefore, OTR(-/-) mice injected with 17?-estradiol do not show any effects on bone formation parameters, while the same treatment increases bone mass in wild-type mice. These findings together provide evidence for an anabolic action of OT in regulating bone mass and suggest that bone marrow OT may enhance the bone-forming action of estrogen through an autocrine circuit. This established new physiological role for OT in the maintenance of skeletal integrity further suggests the potential use of this hormone for the treatment of osteoporosis. PMID:25209411

Colaianni, Graziana; Sun, Li; Zaidi, Mone; Zallone, Alberta

2014-10-15

356

Bone tumor  

MedlinePLUS

Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... include: Genetic defects passed down through families Radiation Injury In ... or metastatic bone tumors. They behave very differently ...

357