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PubMed2003

Infrared analysis of the mineral and matrix in bones of osteonectin-null mice and their wildtype controls.

Osteonectin function in bone was investigated by infrared analysis of bones from osteonectin-null (KO) and wildtype mice (four each at 11, 17, and 36 weeks). An increase in mineral content and crystallinity in newly formed KO bone and collagen maturity at all sites was found using FTIR microspectroscopy and imaging; consistent with osteonectin's postulated role in regulating bone formation and remodeling. Mineral and matrix properties of tibias of osteonectin-null mice and their age- and background-matched wildtype controls were compared using Fourier-transform infrared microspectroscopy (FTIRM) and infrared imaging (FTIRI) at 10- and 7-mm spatial resolution, respectively. The bones came from animals that were 11, 17, and 36 weeks of age. Individual FTIRM spectra were acquired from 20 x 20 microm areas, whereas 4096 simultaneous FTIRI spectra were acquired from 400 x 400 microm areas. The FTIRM data for mineral-to-matrix, mineral crystallinity, and collagen maturity were highly correlated with the FTIRI data in similar regions. In general, the osteonectin-null mice bones had higher mineral contents and greater crystallinity (crystal size and perfection) than the age-matched wildtype controls. Specifically, the mineral content of the newly forming periosteal bone was increased in the osteonectin-null mice; the crystallinity of the cortical bone was decreased in all but the oldest animals, relative to the wildtype. The most significant finding, however, was increased collagen maturity in both the cortical and trabecular bone of the osteonectin-null mice. These spectroscopic data are consistent with a mechanism of decreased bone formation and remodeling.

Animals↗
PubMed1996

[The comparative characteristics of stimulators of reparative osteogenesis in the treatment of periodontal diseases].

The authors compare the efficacy of ultra highly dispersed hydroxyapatite (brand OSTIM-100) and demineralized bone matrix implanted to 395 patients for repair of bone defects. OSTIM-100 was found not inferior to bone transplant, but devoid of its shortcomings. Complications occurred in 1.5% cases and never involved the site of osteoplasty, whereas in the group transplanted bone matrix 3.6% patients developed complications, which were frequently associated with the graft rejection. OSTIM-100 was particularly effective in the treatment of periodontitis at the stage of abscesses. It is convenient and recommended, in combination with membranes of directed regeneration of tissues (GORE-TEX), for surgical treatment of patients with periodontal diseases.

Bone Matrix↗
PubMed1989

Histochemical detection of osteocalcin in normal and pathological human bone.

We investigated the immunohistochemical localization of osteocalcin in demineralized, paraffin-embedded normal and pathological human bone. Acid decalcification protocols appeared to be more suitable for osteocalcin detection than mild chelating agents. In normal lamellar bone, osteocalcin was detected in osteocytes and along the lamellar bone matrix in fine granular deposits. Under pathological conditions (osteomyelitis, neoplasia), appositional bone showed immunoreactivity in osteoblasts and osteocytes but not in the provisory woven bone matrix. Intense immunoreactivity could be seen at the cell borders of osteoclasts and the bone margins of Howship lacunae. In primary bone-forming tumors, osteocalcin immunoreactivity was detected in osteoblasts and their malignant counterparts. On the basis of these results, we conclude that optimal preservation of osteocalcin is obtained through mild acid decalcifiers. Osteocalcin is deposited in bone matrix, especially that of metabolically inactive bone. In neoplasms, osteocalcin could be a marker of osteoblastic differentiation.

Bone Neoplasms↗
PubMed1992

High-resolution immunolocalization of osteopontin and osteocalcin in bone and cartilage during endochondral ossification in the chicken tibia.

The ultrastructural distribution of two noncollagenous proteins, osteopontin (OPN) and osteocalcin (OC), originally extracted from bone matrix and proposed to play an important role in bone formation, was examined in the matrices of bone and cartilage from embryonic and postnatal chicken tibial growth plates by high-resolution immunocytochemistry using the colloidal gold technique. In bone, immunolabeling patterns using polyclonal antibodies against chicken OPN and OC were generally similar in that both showed an intense, but regionally variable, labeling of mineralized bone matrix and small mineralization loci dispersed throughout the osteoid and containing prominent condensed organic material. Unmineralized osteoid showed weak-to-moderate labeling. In the mineralized bone matrix proper, labeling was predominantly associated with amorphous, electron-dense patches of organic material among the collagen fibrils. In growth plate cartilage, both proteins first appeared related to calcified cartilage in the hypertrophic zone, although the labeling patterns were somewhat different. For OPN, gold particles were mostly associated with an organic lamina limitans-like density containing condensed, filamentous organic matrix at the periphery of small nodules and large masses of calcified cartilage, with additional moderate labeling throughout the interior of the calcified cartilage. For OC, labeling was observed over filamentous structures throughout the calcified cartilage matrix, with some, but less, labeling at the periphery. In the lowermost zones of the growth plate, the major reaction using both antibodies was found over a layer of dense, amorphous organic material at the periphery of the calcified cartilage at the future bone/calcified cartilage interface, a labeling pattern that persisted following bone deposition at these sites. OPN and to a lesser extent OC were also concentrated in cement (resting, reversal) lines. Throughout the bone and cartilage of the tibia, cells of both the osteoblastic and the osteoclastic lineages were found directly apposed to labeled surfaces and lamina limitans of organic matrix containing OPN and OC. In summary, it is concluded from the immunocytochemical data presented here that the association of OPN and OC with mineralized regions of the extracellular matrices of bone and cartilage and the accumulation of these proteins at tissue surfaces and interfaces are consistent with the hypotheses that they play a role in the extracellular mineralization process per se and/or that they may mediate cell adhesion and dynamics.

Animals↗
PubMed1994

[Structure and function of bone cells].

Bone modeling and remodeling as well as systemic calcium homeostasis are modulated predominantly by bone cells such as mesencymal-derived osteoblasts and osteocytes and haematopoietic-derived osteoclasts. Osteoblasts are classified into preosteoblasts, mature osteoblasts and bone lining cells (BLC) based on their cell structures and biological functions. Preosteoblasts appear to regulate the activities of mature osteoblasts and osteoclasts as well as to differentiate into mature osteoblasts. Cuboidal mature osteoblasts show well-developed Golgi apparatus and rough endoplasmic reticulum, and synthesize actively major bone matrix proteins including type I collagen, osteopontin, osteonectin and osteocalcin. Unlike mature osteoblasts, BLCs display flattened cell bodies and few cell organelle, therefore, indicating less activities. These osteoblasts communicate through gap junctions and adheres junctions with each other or with osteocytes, consequently forming three-dimensional cellular network in the bone tissues. In contrast, osteocytes, compacted cell type embedded in the bone matrix, provide a cellular environment in the bone matrix by means of their numerous cytoplasmic processes. Moreover, it is likely that they participate in calcium transport from bone matrix to tissue fluid, that is "osteocytic osteolysis". Osteoclasts, multinucleated giant cells with ruffled borders and clear zones, are responsible for bone resorption, although probably they are controlled by surrounding osteoblast phenotype. Active osteoclasts secrete H+ and proteolytic enzyme such as cathepsin and ACPase towards resorption pits through ruffled borders. These bone cells play an important role in bone modeling and remodeling.

Animals↗
PubMed1998

Osteoinductive potential of demineralized rat bone increases with increasing donor age from birth to adulthood.

Demineralized allogenic bone implanted in the subcutis or muscle of rodents causes formation of heterotopic bone by osteoinduction. The osteoinductive response may be weaker in primates than in rodents. It was suggested that the osteoinductive response of demineralized bone for clinical use could be enhanced by using young donors, because studies have indicated that the osteoinductive response is reduced in demineralized bone of old versus young donors. However, these findings may not represent a gradual decline in the osteoinductive property of bone matrix throughout the life span. We evaluated quantitatively, by uptake of strontium 85, the osteoinductive effect of demineralized bone matrix from newborn, 8-week-old (adolescent), and 8-month-old (adult) male Wistar rats implanted in the abdominal muscles of 8-week-old male Wistar rats. The osteoinductive response increased significantly with increasing donor age. The results of the present study, weighed with those of previous studies, indicate that the osteogenic potential of the bone matrix increases from newborn to adulthood but decreases in the aged rat. This may be due to changes in concentration of essential growth factors (e.g., bone morphogenetic proteins) resulting from maturational changes from birth to adulthood and osteoporotic changes occurring in later years. The results do not support the contention that young donors of demineralized bone are preferable to adult donors.

Abdominal Muscles↗
PubMed1987

Diaphyseal reconstruction by autoclaved bone. Reimplantation experiments in rabbits.

In 8 adult rabbits, reconstruction of large humeral defects by reimplantation of resected, autoclaved bone supplemented with allogeneic bone matrix was investigated with respect to incorporation (radiography, histology), bone metabolic activity (scintigraphy, autoradiography), and strength (torsional test). Radiography showed that seven out of eight implants were incorporated at 3 months. Scintigraphy and autoradiography disclosed bone metabolic activity in the reconstructions still 8 months postoperatively. Histological investigations evidenced abundant new viable bone that partially had replaced the implants at 8 months. The torsional test disclosed that the strength of the reconstructions was 84 per cent of normal 8 months after reimplantation. Our experiment supports the concept of reimplantation of autoclaved tumorous bone supplemented with allogeneic bone matrix in reconstruction after local resection.

Animals↗
PubMed1998

Multi-center clinical evaluation of combination anorganic bovine-derived hydroxyapatite matrix (ABM)/cell binding peptide (P-15) as a bone replacement graft material in human periodontal osseous defects. 6-month results.

A synthetic cell-binding peptide (P-15) combined with anorganic bovine-derived hydroxyapatite bone matrix (ABM) was compared to demineralized freeze-dried bone allograft (DFDBA) and open flap debridement (DEBR) in human periodontal osseous defects in a controlled, monitored, multi-center trial. Following appropriate initial preparation procedures, flap surgery with defect and root debridement was performed. Three osseous defects per patient were treated randomly with one of three procedures after surgical preparation. Appropriate periodontal maintenance schedules were followed, and at 6 to 7 months re-entry flap surgery was performed for documentation and finalization of treatment. Analysis of variation (ANOVA) and t test analyses of patient mean values from 31 patients revealed that the combination ABM/P-15 grafts demonstrated significantly better mean defect fill of 2.8 +/- 1.2 mm (72.3%) versus a mean defect fill of 2.0 +/- 1.4 mm (51.4%) for defects treated with DFDBA (P <0.05) and a mean defect fill of 1.5 +/- 1.3 mm (40.3%) (P <0.05) for defects treated with DEBR. Other hard tissue findings showed similar clinically superior results with the use of ABM/P-15. Relative defect fill results showed 87% positive (50% to 100% defect fill) responses with ABM/P-15, 58% positive responses with DFDBA, and 41% positive responses with DEBR. There were 8 to 9 times more failures (minimal response) with DFDBA and DEBR (26% to 29% frequency) than with ABM/P-15. Soft tissue findings showed no significant differences among treatments except for greater clinical attachment level gain with ABM/P-15 compared to DEBR. These results suggest that the use of the P-15 synthetic cell-binding peptide combined with ABM yields better clinical results than either DFDBA or DEBR. Further studies are needed to determine the relative roles of the ABM and/or the P-15 in these improved results.

Adult↗
PubMed1998

Regulation of osteocalcin production and bone resorption by 1,25-dihydroxyvitamin D3 in mouse long bones: interaction with the bone-derived growth factors TGF-beta and IGF-I.

Bone cells produce multiple growth factors that have effects on bone metabolism and can be incorporated into the bone matrix. Interplay between these bone-derived growth factors and calciotropic hormones has been demonstrated in cultured bone cells. The present study was designed to extend these observations by examining the interactions between either transforming growth factor-beta (TGF-beta) or insulin-like growth factor-I (IGF-I) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in a mouse long bone culture model with respect to osteocalcin production and bone resorption. In contrast to the stimulation in rat and human, in the fetal mouse long bone cultures, 1,25(OH)2D3 caused a dose-dependent inhibition of osteocalcin production. Both the osteocalcin content in the culture medium and in the extracts of the long bones was reduced by 1,25(OH)2D3. This effect was not specific for fetal bone because 1,25(OH)2D3 also reduced osteocalcin production by the neonatal mouse osteoblast cell line MC3T3. TGF-beta inhibited whereas IGF-I dose-dependently increased osteocalcin production in mouse long bones. The combination of TGF-beta and 1,25(OH)2D3 did not result in a significantly different effect compared with each of these compounds alone. The IGF-I effect was completely blocked by 1,25(OH)2D3. In the same long bones as used for the osteocalcin measurements, we performed bone resorption analyses. Opposite to its effect on osteocalcin, 1,25(OH)2D3 dose-dependently stimulated bone resorption. TGF-beta reduced and IGF-I did not change basal (i.e., in the absence of hormones) bone resorption. Our results show that 1,25(OH)2D3-enhanced bone resorption is dose-dependently inhibited by TGF-beta and IGF-I. Regression analysis demonstrated a significant negative correlation between 1,25(OH)2D3-induced bone resorption and osteocalcin production. The specificity for their effect on 1,25(OH)2D3-stimulated bone resorption was assessed by testing the effects of TGF-beta and IGF-I in combination with parathyroid hormone (PTH). Like 1,25(OH)2D3, PTH dose-dependently stimulates bone resorption. However, PTH-stimulated bone resorption was not affected by TGF-beta. Like 1,25(OH)2D3-stimulated bone resorption, IGF-I inhibited the PTH effect but at a 10-fold higher concentration compared with 1,25(OH)2D3. In conclusion, the present study demonstrates growth factor-specific interactions with 1,25(OH)2D3 in the control of osteocalcin production and bone. With respect to bone resorption, these interactions are also hormone specific. The present data thereby support and extend the previous observations that interactions between 1,25(OH)2D3 and bone-derived growth factors play an important role in the control of bone metabolism. These data together with the fact that TGF-beta and IGF-I are present in the bone matrix and potentially can be released during bone resorption support the concept that growth factors may control the effects of calciotropic hormones in bone in a localized and possibly temporal manner. Finally, in contrast to human and rat, in mice 1,25(OH)2D3 reduces osteocalcin production and this reduction is paralleled by stimulation of bone resorption by 1,25(OH)2D3. These data thereby show a dissociation between osteocalcin production and bone resorption.

Animals↗
PubMed2002

[An experimental study on repair of laryngeal cartilage defect with the bone morphogenetic protein composite].

OBJECTIVE: To study the effects of the bone matrix gelatin and composite of bone morphogenetic protein and fibrin glue (BMP-FG) on the repair of thyroid cartilage defect. METHOD: Full-thickness defects measuring 0.4 cm x 0.4 cm were created in four sections in thyroid cartilages of 20 adult dogs. The defects were divided into 4 groups by the sections they in. Group A was empty group, without implant; Group B were repaired by implanted with hydroxylapatite; Group C with bone matrix gelatin (containing BMP); Group D with bone morphogenetic protein-fibrin glue composite. The animals were killed separately at 2, 4, 12 weeks after operation. The effects of repair were analyzed by routine histological examination and electron microscope. RESULT: In the BMP-FG implanted group, the result showed complete absorption of the implant and substitution by new-formed cartilage and bone. The defects in the BMG group regenerated less cartilage and bone, the inflammation was sever. The gross appearance and histological features of HA group were similar to the empty group. CONCLUSION: Both BMP-FG and BMG can induce cartilage and bone regeneration to repair the defect of thyroid cartilage. BMP-FG has a better effect.

Animals↗
PubMed2002

Influence of cage design on interbody fusion in a sheep cervical spine model.

OBJECT: The purpose of this study was to compare the characteristics of interbody fusion achieved using an autologous tricortical iliac crest bone graft with those of a cylinder- and a box-design cage in a sheep cervical spine model. This study was designed to determine whether there are differences between three interbody fusion procedures in: 1) ability to preserve postoperative distraction; 2) biomechanical stability; and 3) histological characteristics of intervertebral bone matrix formation. METHODS: Twenty-four sheep underwent C3-4 discectomy and fusion in which the following were used: Group 1, autologous tricortical iliac crest bone graft (eight sheep); Group 2, titanium cylinder-design cage filled with autologous iliac crest bone graft (eight sheep); and Group 3, titanium box-design cage filled with autologous iliac crest graft (eight sheep). Radiography was performed pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks. At the same time points, disc space height, intervertebral angle, and lordosis angle were measured. After 12 weeks, the sheep were killed, and fusion sites were evaluated by obtaining functional radiographs in flexion and extension. Quantitative computerized tomography scans were acquired to assess bone mineral density, bone mineral content, and bone callus volume. Biomechanical testing was performed in flexion, extension, axial rotation, and lateral bending. Stiffness, range of motion, neutral zone, and elastic zone were determined. Histomorphological and histomorphometric analyses were performed, and polychrome sequential labeling was used to determine the time frame of new bone formation. Over a 12-week period significantly higher values for disc space height and intervertebral angle were shown in cage-treated sheep than in those that received bone graft. Functional radiographic assessment revealed significantly lower residual flexion-extension movement in sheep with the cylinder cage-fixed spines than in those that received bone graft group. The cylinder-design cages showed significantly higher values for bone mineral content, bone callus content, and stiffness in axial rotation and lateral bending than the other cages or grafts. Histomorphometric evaluation and polychrome sequential labeling showed a more progressed bone matrix formation in the cylindrical cage group than in both other groups. CONCLUSIONS: Compared with the tricortical bone graft, both cages showed significantly better distractive properties. The cylindrical cage demonstrated a significantly higher biomechanical stiffness and an accelerated interbody fusion compared with the box-design cage and the tricortical bone graft. The differences in bone matrix formation within both cages were the result of the significantly lower stress shielding on the bone graft by the cylinder-design cage.

Animals↗
PubMed1997

Regulation of MMP-9 (92 kDa type IV collagenase/gelatinase B) expression in stromal cells of human giant cell tumor of bone.

Matrix metalloproteinases (MMPs) play an important regulatory role in tissue morphogenesis, cell differentiation, tumor invasion and metastasis. Several authors have reported a direct correlation between the production of 72 kDa (MMP-2) and 92 kDa (MMP-9) type IV collagenases/gelatinases and the metastatic potential of cancer cells. Recently, we have identified the expression of both MMP-2 and MMP-9 in primary cultures of human giant cell tumor (GCT) of bone in vitro, and in tissue extracts in vivo. Interestingly, MMP-9 is not secreted by late-passaged GCT cells. It is possible that the production of MMP-9 is regulated by certain factor(s) secreted by the multinucleated giant cells in the primary culture. In order to test this hypothesis, the effect of primary-culture-conditioned medium on the expression of MMP-9 by late-passaged mononuclear stromal cells was examined. Adding conditioned medium from the primary GCT culture to the late-passaged stromal cells induced MMP-9, as evidenced by the presence of lytic bands at M(r) 92,000 and 72,000 on a gelatin zymogram. These enzyme activities were inhibited by EDTA, a well-known inhibitor of the MMPs. We confirmed these results by Western blotting using specific antibodies and RT-PCR for MMP-2 and MMP-9. Immunofluorescence studies with specific antibodies to MMP-9 further confirmed its expression by the passaged stromal cells cultured in the primary-culture-conditioned medium. The data indicate that MMP-2 and MMP-9 are produced by the mononuclear stromal cells when cultured in GCT primary-culture-conditioned medium. This suggests that multinucleated giant cells in primary cultures secrete a factor(s) that stimulates stromal cells to produce MMP-9, which, in turn, may contribute to the aggressive behavior of GCT.

Adolescent↗
PubMed1993

Temporal changes during bone regeneration in the calvarium induced by osteogenin.

Repair of rat craniotomy defects, 8 mm in diameter, was compared with that of defects treated with either rat insoluble collagenous bone matrix (ICBM) or partially purified bovine osteogenin, a bone-inductive protein, reconstituted with ICBM (OG/ICBM). Repair of all defects was similar histologically throughout the first 3 days, characterized by acute, then chronic inflammation and granulation tissue formation. In defects treated with OG/ICBM, cartilage and osteoblasts were present at day 5. By day 9, cartilage and osteoid production were active. New bone showed hematopoietic tissue by day 11; a complete bone bridge was established by day 21. By day 42, fatty marrow was present. Defects treated with ICBM alone showed islands of cartilage and bone embedded in connective tissue at day 9, which reached peak maturity by day 14. In these and in untreated defects, significant osteoblastic and osteoclastic activity, located primarily at the margins of the defects, subsided by day 28. Untreated defects gradually filed in with fibrous connective tissue which matured throughout 156 days. Radiopacity, quantified by computerized image analysis, increased significantly between days 9 and 11 in OG/ICBM-treated defects, and remained greater (P < 0.05) than that of the ICBM-treated defects. There was a more gradual increase in radiopacity in ICBM-treated defects. The sequence of morphologic events during calvarial bone regeneration was very similar to that described previously for heterotopic bone formation induced by demineralized bone matrix.

Animals↗
PubMed1997

Suppressed bone induction by follistatin in spontaneously hypercholesterolemic rat bone.

Bone inducing activity in demineralized bone matrix (DBM) of young spontaneously hypercholesterolemic (SHC) rats has been shown to be lower than that of aged SHC rats. This study examined the involvement of bone follistatin, an activin-binding protein, in bone induction. Immunoreactive follistatin was higher in DBM from 10-week-old SHC rats (DBM-10wk) than in DBM from 6-month-old SHC rats (DBM-6mo). When DBM without follistatin supplement was implanted, the C-propeptide of type II procollagen and calcium contents on day 12 in implants of DBM-6mo were 68% and 40% higher than those of DBM-10wk, respectively. In contrast, follistatin supplement to DBM decreased C-propeptide of type II procollagen and calcium contents in implants of both DBM-10wk and DBM-6mo, and the levels of these parameters were comparable between DBM-10wk and DBM-6mo, indicating reduced formation of cartilage and bone. These findings suggest that 1) follistatin content in bone matrix decreases with advancing age in SHC rats, and 2) the follistatin interferes with endochondral bone formation. We demonstrate that the lower bone induction of DBM from young SHC rats was partly due to the abundance of follistatin in bone matrix.

Aging↗
PubMed1991

Bone-derived growth factors modulate collagenase and TIMP (tissue inhibitor of metalloproteinases) activity and type I collagen degradation by mouse calvarial osteoblasts.

The finding that osteoblasts synthesize collagenase has led to the hypothesis that bone cells play a major role in bone resorption by degrading the surface osteoid layer, thereby preparing the underlying mineralized bone for osteoclastic action. To further understand the mechanisms regulating osteoid removal, mouse calvarial osteoblasts were cultured on 14C-labelled type I collagen films and the abilities of (i) bovine bone matrix extracts and (ii) purified or recombinant human growth factors, to modify their collagenolytic behaviour were investigated. EDTA/Tris-HCl extracts of bone matrix containing growth factor activity, exerted a dose-dependent inhibition of type I collagenolysis by osteoblasts stimulated with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, 10 ng/ml). Inhibition was accompanied by a reduction in collagenase activity and an increase in free TIMP (tissue inhibitor of metalloproteinases) in the culture medium. Transforming growth factor-beta, epidermal growth factor, platelet-derived growth factor and the acidic and basic fibroblast growth factors all mimicked these effects. In contrast, insulin-like growth factors-I and -II did not inhibit type I collagenolysis, only partially inhibited collagenase activity, and did not stimulate TIMP production by either 1,25(OH)2D3-treated or untreated cells. These findings provide additional evidence for the tight control exerted on the proteolytic activity of osteoblasts and the importance of TIMP in its regulation. They suggest strongly that the conversion (coupling) of the initial resorptive phase of the bone remodelling cycle to one of deposition, may be mediated by polypeptide growth factors either produced locally by osteoblasts, or released by proteolysis from the bone matrix.

Animals↗
PubMed2004

Alphavbeta integrins play an essential role in BMP-2 induction of osteoblast differentiation.

UNLABELLED: Both integrins and BMP-2 exert similar effects on osteoblasts. We examined the relationship between the alphav-containing integrins (alphavbeta) and BMP-2 in osteoblast function. BMP-2 stimulates alphavbeta expression. BMP-2 receptors co-localize/overlap with alphavbeta integrins, and the intact function of alphavbeta is essential in BMP-2 activity. INTRODUCTION: Bone morphogenetic protein (BMP)-2 not only induces osteoblast differentiation and bone matrix mineralization, but also stimulates osteoblast migration on and adhesion to bone matrix proteins. The alphavbeta- and beta1- (alphabeta1) containing integrins mediate osteoblast interaction with many bone matrix proteins and play important roles in osteoblast adhesion, migration, and differentiation. Because alphavbeta integrins and BMP-2 share common effects on osteoblasts, we analyzed their relationship in osteoblast function. MATERIALS AND METHODS: The effects of BMP-2 on integrin expression were determined by surface labeling/immunoprecipitation and cell adhesion to matrix proteins. Confocal analysis of the immunostained cells and co-immunoprecipitation of cell extracts were used to study the spatial relationship between integrins and BMP-2 receptors. A function-blocking anti-alphavbeta integrin antibody (L230) was employed to investigate the roles of alphavbeta integrins in BMP-2 function. RESULTS: Human osteoblasts (HOBs) express alphabeta1, alphavbeta3, alphavbeta5, alphavbeta6, and alphavbeta8 integrins at focal adhesion sites. BMP-2 increases the levels of these integrins on osteoblast surface and enhances HOB adhesion to osteopontin and vitronectin. Immunoprecipitation and immunostaining analyses show that BMP-2 receptors co-localize or overlap with alphavbeta and alphabeta1 integrins. Incubation of HOBs with L230 abolishes the antiproliferative effect of BMP-2 and reduces the capacity of BMP-2 to stimulate alkaline phosphatase activity and the expression of osteocalcin, osteopontin, and bone sialoprotein. Furthermore, L230 prevents BMP-2 induction of matrix mineralization. Although BMP-2 retains its receptor-binding capability in the presence of L230, BMP-2 stimulation of Smad signaling is abolished by L230. CONCLUSION: BMP-2 upregulates the expression of alphavbeta integrins, and these integrins, in turn, play a critical role in BMP-2 function in osteoblasts.

Alkaline Phosphatase↗
PubMed2000

The cell biology of osteoclast function.

Osteoclasts are multinucleated cells responsible for bone resorption. They have developed an efficient machinery for dissolving crystalline hydroxyapatite and degrading organic bone matrix rich in collagen fibers. When initiating bone resorption, osteoclasts become polarized, and three distinct membrane domains appear: a ruffled border, a sealing zone and a functional secretory domain. Simultaneously, the cytoskeleton undergoes extensive re-organisation. During this process, the actin cytoskeleton forms an attachment ring at the sealing zone, the membrane domain that anchors the resorbing cell to bone matrix. The ruffled border appears inside the sealing zone, and has several characteristics of late endosomal membrane. Extensive vesicle transport to the ruffled border delivers hydrochloric acid and proteases to an area between the ruffled border and the bone surface called the resorption lacuna. In this extracellular compartment, crystalline hydroxyapatite is dissolved by acid, and a mixture of proteases degrades the organic matrix. The degradation products of collagen and other matrix components are endocytosed, transported through the cell and exocytosed through a functional secretory domain. This transcytotic route allows osteoclasts to remove large amounts of matrix-degradation products without losing their tight attachment to underlying bone. It also facilitates further processing of the degradation products intracellularly during the passage through the cell.

Animals↗