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PubMed2003

Reduction of osteoclasts in a critical embryonic period is essential for inhibition of mouse tooth eruption.

Alveolar bone resorption by osteoclasts is essential for tooth eruption. Osteoclast-deficient Csfm(op) homozygous (op/op) mice, which lack functional macrophage colony-stimulating factor (M-CSF), suffer from osteopetrosis and completely lack tooth eruption. Although osteoclasts appear, and osteopetrosis is cured with age in op/op mice, tooth eruption is never seen. This fact suggests that there is a critical period when osteoclasts are required for tooth eruption. In this study, to detect the critical period, we administered an antagonistic antibody directed against c-Fms, a receptor for M-CSF, to inbred C57BL/6 mice for various periods. Administration of this antibody decreased tartrate-resistant acid phosphatase-positive (TRAP) osteoclasts, and incisor eruption was completely inhibited by continual administration of this antibody from embryonic day 15.5 (E15.5) until postnatal day 12.5 (D12.5). A 1-day delay of this administration abolished the inhibition of incisor eruption. The number of TRAP-positive osteoclasts was significantly reduced between E16.5 and E18.5 in the mice treated with antibody from E15.5 compared with those treated from E16.5. These results indicate that this period, during which the number of osteoclasts decreases significantly, is critical for inhibiting incisor eruption in C57BL/6 mice.

Acid Phosphatase↗

PubMed2005

Osteoclast responses to lipopolysaccharide, parathyroid hormone and bisphosphonates in neonatal murine calvaria analyzed by laser scanning confocal microscopy.

Because the development and activity of osteoclasts in bone remodeling is critically dependent on cell-cell and cell-matrix interactions, we used laser confocal microscopy to study the response of osteoclasts to lipopolysaccharide (LPS; 10 microg/ml), parathyroid hormone (PTH; 10(-8) M), and bisphosphonates (BPs; 1-25 microM clodronate or 0.1-2.5 microM risedronate) in cultured neonatal calvaria. Following treatment with LPS or PTH (<48 hr), osteopontin (OPN) and the alphavbeta3 integrin were found colocalized with the actin ring in the sealing zone of actively resorbing osteoclasts. In contrast, non-resorbing osteoclasts in BP-treated cultures showed morphological abnormalities, including retraction of pseudopods and vacuolization of cytoplasm. In the combined presence of LPS and BP, bone-resorbing osteoclasts were smaller and the sealing zone diffuse, reflecting reduced actin, OPN, and beta3 integrin staining. Depth analyses of calvaria showed that the area of resorbed bone was filled with proliferating osteoblastic cells that stained for alkaline phosphatase, collagen type I, and bone sialoprotein, regardless of the presence of BPs. These studies show that confocal microscopy of neonatal calvaria in culture can be used to assess the cytological relationships between osteoclasts and osteoblastic cells in response to agents that regulate bone remodeling in situ, avoiding systemic effects that can compromise in vivo studies and artifacts associated with studies of isolated osteoclasts.

Acid Phosphatase↗

PubMed1999

Human osteoclast ontogeny and pathological bone resorption.

Monocytes and macrophages are capable of degrading both the mineral and organic components of bone and are known to secrete local factors which stimulate host osteoclastic bone resorption. Recent studies have shown that monocytes and macrophages, including those isolated from neoplastic and inflammatory lesions, can also be induced to differentiate into cells that show all the cytochemical and functional characteristics of mature osteoclasts, including lacunar bone resorption. Monocyte/macrophage-osteoclast differentiation occurs in the presence of osteoblasts/bone stromal cells (which express osteoclast differentiation factor) and macrophage-colony stimulating factor and is inhibited by osteoprotegerin. Various systemic hormones and local factors (e.g. cytokines, growth factors, prostaglandins) modulate osteoclast formation by controlling these cellular and humoral elements. Various pathological lesions of bone and joint (e.g. carcinomatous metastases, arthritis, aseptic loosening) are associated with osteolysis. These lesions generally contain a chronic inflammatory infiltrate in which macrophages form a significant fraction. One cellular mechanism whereby pathological bone resorption may be effected is through generation of increased numbers of bone-resorbing osteoclasts from macrophages. Production of humoral factors which stimulate mononuclear phagocyte-osteoclast differentiation and osteoclast activity is also likely to influence the extent of pathological bone resorption.

Animals↗

PubMed2006

Genetics and genomics of osteoclast differentiation: integrating cell signaling pathways and gene networks.

The regulation of osteoclast differentiation in the bone microenvironment is critical for normal bone remodeling, as well as for various human bone diseases. Over the last decade, our knowledge of how osteoclast differentiation occurs has progressed rapidly. We highlight some of the major advances in understanding how cell signaling and transcription are integrated to direct the differentiation of this cell type. These studies used genetic, molecular, and biochemical approaches. Additionally, we summarize data obtained from studies of osteoclast differentiation that used the functional genomic approach of global gene profiling applied to osteoclast differentiation. This genomic data confirms results from studies using the classical experimental approaches and also may suggest new modes by which osteoclast differentiation and function can be modulated. Two conclusions that emerge are that osteoclast differentiation depends on a combination of fairly ubiquitously expressed transcription factors rather than unique osteoclast factors, and that the overlay of cell signaling pathways on this set of transcription factors provides a powerful mechanism to fine tune the differentiation program in response to the local bone microenvironment.

Animals↗

PubMed2003

In vitro studies with the calcimimetic, cinacalcet HCl, on normal human adult osteoblastic and osteoclastic cells.

This study examined whether the calcium-sensing receptor (CaR) is expressed in normal adult human osteoblastic and osteoclastic cells in culture, and whether the calcimimetic, cinacalcet HCl (AMG 073), potentiates the effects of calcium (via CaR, or some other receptor/mechanism). When mouse or human osteoblastic cells were treated with higher concentrations of calcium (6.6 or 8.6 mM in alpha-MEM/10% FBS) than present in control cultures (1.6 mM), the previously well-documented increase in cell number was demonstrated. Cinacalcet HCl affected cell proliferation of CHO cells transfected with CaR, dose dependently, but had no effect on human or mouse osteoblastic cell proliferation in calcium-containing medium (1.6 or 8.6 mM). To test cinacalcet HCl and calcium on osteoclastic cells, peripheral blood mononuclear cells were cultured in medium containing RANK ligand and M-CSF, supplemented with calcium, and/or cinacalcet HCl. Tartrate-resistant acid phosphatase-positive multinucleated osteoclastic cells on plastic or bone were then counted at 11 and 21 days, respectively. Calcium (greater than 6.0 mM) inhibited osteoclast formation, but cinacalcet HCl (30-1000 nM) had no effect on osteoclastic formation or resorption in the presence of calcium (1.6 or 6.1 mM). RT-PCR did not detect CaR in human, rat, or mouse primary osteoblastic cells and cell lines or osteoclastic cells. In conclusion, these studies indicate that the calcium-induced increase in osteoblastic cell number, and the decrease in formation/function of osteoclastic cells, involves a mechanism or receptor other than CaR. In addition, the calcimimetic agent did not potentiate the effects of calcium on normal adult human bone cells in vitro.

Animals↗

PubMed2005

Osteoclast-like cells express receptor activity modifying protein 2: application of laser capture microdissection.

Receptor activity modifying proteins (RAMPs) act as receptor modulators that determine the ligand specificity of receptors for the calcitonin (CT) family. The purpose of this study was to analyze the expression of RAMPs in osteoclast-like cells using the laser capture microdissection (LCM) technique. Mouse bone marrow and spleen cells were co-cultured on a film designed for LCM. After 10 days, 250 osteoclast-like cells were captured using the LCM system. Total RNA from these cells was used to synthesize cDNA and RT-PCR analysis was performed. Osteoclast-like cells expressed CT receptor (CTR), CT receptor-like receptor (CRLR) and RAMP2, but did not express RAMP1 or RAMP3. These results indicated (1) that a pure population of osteoclast-like cells can be prepared by LCM and gene expression of this population can be analyzed by RT-PCR and (2) that RT-PCR shows that osteoclast-like cells express RAMP2, CTR and CRLR, suggesting the potential for adrenomedullin binding to osteoclast-like cells. This is the first report that osteoclast-like cells express RAMP2.

Animals↗

PubMed1996

Selective toxic effects of tamoxifen on osteoclasts: comparison with the effects of oestrogen.

We investigated the actions of the trans- and cis-isomers of tamoxifen on the function of neonatal rat osteoclasts in vitro. Both compounds inhibited resorption pit formation by osteoclast-containing mixed bone cell cultures incubated for 24 h on cortical bone slices. Cell counts revealed that the inhibition was closely related to a cytotoxic effect, to which osteoclasts appeared particularly sensitive. Partial inhibition of resorption was seen in the presence of 2 microM trans-tamoxifen, whereas complete abolition of resorption and osteoclast viability occurred with 10 microM trans-tamoxifen; survival of mononuclear cells was unimpaired at either concentration. Cis-tamoxifen appeared to be slightly more toxic, with significant inhibitions of osteoclast viability and thus resorption pit formation at a concentration of 2 microM, and also of mononuclear cell numbers at 10 microM. Time-lapse video observations indicated that osteoclast death occurred rapidly (within 2-3 h) following exposure to 10 microM of either trans-tamoxifen or cis-tamoxifen. The morphological appearance of the dying cells was consistent with apoptosis. These results may help to explain the anti-resorptive action of tamoxifen seen in vivo in rats and humans. In contrast, oestradiol-17 beta consistently exerted no significant effects on resorption pit formation by rat osteoclasts over 24 h, even at grossly supraphysiological concentrations (up to 10 microM).

Animals↗

PubMed1997

Angiotensin II is generated from angiotensin I by bone cells and stimulates osteoclastic bone resorption in vitro.

During bone resorption, osteoclasts are closely associated with endothelial cells. The latter are able to produce several agents that regulate bone resorption. In view of the increasing evidence that angiotensin II, which can be generated by endothelial cells, has actions outside the traditional renin-angiotensin system, we tested the effect of angiotensin II on bone resorption Angiotensin II showed no effect either on osteoclast formation or on bone resorption by isolated osteoclasts. However, in co-cultures of osteoclasts with calvarial or MC3T3-E1 osteoblastic cells, and in osteoclastic cultures co-cultured with other bone cells obtained by prolonged sedimentation, angiotensin II stimulated bone resorption to a similar degree to that observed with 1,25(OH)2 vitamin D3. Stimulation of resorption was noted at concentrations of 10(-7) M and above. We found that angiotensin I also stimulated bone resorption in co-cultures of osteoclasts with osteoblastic cells, and that this action was inhibited by inhibitors of angiotensin-converting enzyme. These results identify angiotensin I and II as potent stimulators of osteoclastic bone resorption, and raise the possibility that bone might contain a tissue-renin-angiotensin system that might play a role in the regulation of bone resorption.

Angiotensin I↗

PubMed2001

Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, is involved in osteoclastogenesis under calcitonin-regulated conditions.

Although calcitonin has been clinically utilized as a primary treatment for several metabolic bone diseases, its inhibitory effects against osteoclastic function diminish after several days owing to the calcitonin 'escape phenomenon'. We have previously found a unique cell-surface antigen (Kat1-antigen) expressed on rat osteoclasts. Here we show evidence that, in the presence of calcitonin, the Kat1-antigen is involved in osteoclastogenesis. Treatment of bone marrow cultures for forming osteoclast-like cells with anti-Kat1-antigen monoclonal antibody (mAb Kat1) provoked a marked stimulation of osteoclast-like cell formation only in the presence of calcitonin but not in its absence. Osteoclastogenesis stimulated by the receptor activator of nuclear factor kappa B (NF-kappaB) ligand/osteoclast differentiation factor was further augmented by mAb Kat1 in the presence of calcitonin. Furthermore, even in the presence of the osteoprotegerin/osteoclast inhibitory factor, mAb Kat1 induced osteoclast-like cell formation. Our current data suggest that the Kat1-antigen is a molecule that is distinct from receptor activator of NF-kappaB. The presence of the unique Kat1-antigen on cells in the osteoclast lineage appears to contribute to the fine regulation of osteoclastogenesis in vivo. Expression of this cell-surface molecule in cells in the osteoclast lineage may partly explain the mechanism responsible for the escape phenomenon.

Analysis of Variance↗

PubMed2002

Effect of corticosteroids on human osteoclast formation and activity.

Chronic corticosteroid treatment is known to induce bone loss and osteoporosis. Osteoclasts are specialised bone-resorbing cells that are formed from mononuclear phagocyte precursors that circulate in the monocyte fraction. In this study we have examined the effect of the synthetic glucocorticoid, dexamethasone, on human osteoclast formation and bone-resorbing activity. Human monocytes were cultured for up to 21 days on glass coverslips and dentine slices, with soluble receptor activator for nuclear factor kappaB ligand (RANKL; 30 ng/ml) and human macrophage-colony stimulating factor (M-CSF; 25 ng/ml) in the presence and absence of dexamethasone (10(-8) M). The addition of dexamethasone over a period of 7 and 14 days of culture of monocytes (during which cell proliferation and differentiation predominantly occurred) resulted in a marked increase in the formation of tartrate-resistant acid phosphatase-positive multinucleated cells and an increase in lacunar resorption. The addition of dexamethasone to monocyte cultures after 14 days (when resorptive activity of osteoclasts had commenced) reduced the extent of lacunar resorption compared with cultures to which no dexamethasone had been added. The addition of dexamethasone to osteoclasts isolated from giant cell tumours of bone significantly inhibited resorption pit formation. Our findings indicate that dexamethasone has a direct effect on osteoclast formation and activity, stimulating the proliferation and differentiation of human osteoclast precursors and inhibiting the bone-resorbing activity of mature osteoclasts.

Acid Phosphatase↗

PubMed2001

Effects of whole cell sonicates of Treponema lecithinolyticum on osteoclast differentiation.

BACKGROUND: Alveolar bone destruction is a characteristic feature of periodontal diseases and multinucleated osteoclast cells derived from hemopoietic cells are responsible for bone resorption. Treponema lecithinolyticum is a novel oral spirochete isolated from the periodontal lesions. METHODS: The effect of whole cell sonicates on the osteoclast differentiation was examined in a co-culture system of hemopoietic mouse bone marrow cells and calvaria derived-osteoblastic cells to clarify the role of T. lecithinolyticum in the alveolar bone destruction associated with periodontal diseases. The differentiated osteoclasts were confirmed by tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: Sonicates of this bacterium stimulated the osteoclast formation in the co-culture system in a dose-dependent manner. The sonicates-induced osteoclast formation was partially inhibited by the heat treatment of sonicates. Indomethacin, which is a prostaglandin inhibitor, decreased the osteoclast formation induced by the bacterial sonicates. CONCLUSIONS: These findings suggest that T. lecithinolyticum induces osteoclast differentiation by a prostaglandin E2-dependent mechanism and that heat-labile components may be involved in this process.

Alveolar Bone Loss↗

PubMed2002

Selective inhibition of osteoclast vacuolar H(+)-ATPase.

The proton pump expressed on the plasma membrane of bone resorbing osteoclasts, and which mediates the acidification of the extracellular environment in resorption lacuna, belongs to the family of vacuolar H(+)-ATPases, which are enzymes ubiquitously distributed among all cells and are evolutionary conserved. These pumps have two functional domains: a peripherally associated cytoplasmatic section, and a proton channel composed of several subunits one of which, the 116 kDa subunit, is expressed exclusively in osteoclasts and confers unique functional and pharmacological properties to the osteoclast V-ATPase. It was demonstrated that inhibition of this pump can abolish bone resorption; therefore, osteoclast-selective inhibitors could provide novel and useful agents for the treatment of osteoporosis. This paper reviews the medicinal chemistry approaches that have allowed to obtain such new agents, most of which have been designed starting from the natural macrolide antibiotic bafilomycin A(1), a potent and selective inhibitor of all V-ATPases. Identification of SAR and of minimal structural requirements for bafilomycin activity have allowed to obtain (2Z,4E)-5-(5,6-dichloroindolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pentadienamide (SB-242784) which inhibits the osteoclastic proton pump and bone resorption in vitro. Although it inhibits the activity of non-osteoclastic proton pumps as well, it appears to have reasonable selectivity and its administration for 6 months prevented the loss of femoral and vertebral BMD in ovariectomized rats, without any significant renal effects in control and acid-loaded animals. Other independent approaches that did not start from bafilomycin have led to the discovery of a different class of V-ATPase inhibitors, among which 4-(2,6-dichlorobenzoyl)amino-2-trifluoromethyl(benzoimidazol-1-yl)acetyl morpholine (FR177995) was the most effective in preventing bone resorption in an ovariectomized rat model of osteoporosis. These compounds are of great pharmaceutical and medical interest because they allow to target a specific function of the osteoclast; however, only clinical trials might demonstrate whether they have significant advantages over other inhibitors of bone resorption for the treatment of osteoporosis.

Animals↗

PubMed1998

Rat osteoclast precursors in vivo express a vitronectin receptor and a chloride-bicarbonate exchanger.

In vivo osteoclast precursors, which are mononuclear, were previously found to express TRAP (tartrate-resistant acid phosphatase) and CTR (calcitonin receptor), like multinucleated osteoclasts. In vitro, they were found to express, in addition, VNR (vitronectin receptor) and CBE (chloride-bicarbonate exchanger). In order to ascertain that osteoclast precursors in vivo express VNR and CBE like their in vitro counterparts, we used immunohistochemistry to localize these molecules in developing long bones of neonatal rats. Frozen sections of metatarsals and phalanges of 1-2 day-old rats were stained for TRAP and mineralization using histochemistry or were reacted with polyclonal antibodies specific for either the beta3 chain of the VNR or synthetic sequences of the CBE. Both mature, multinucleated osteoclasts within the forming marrow cavity of metatarsals (as shown previously) and mononuclear osteoclast precursors located outside the bony collar of the phalangeal calcified rudiment (as shown here for the first time) expressed both TRAP, VNR and CBE. These findings suggest that mononuclear osteoclast precursors express many of the phenotypical markers of multinucleated osteoclasts prior to their fusion and multinucleation which may allow them to resorb bone, as suggested by in vitro observations of pit formation by preosteoclasts cultured on resorbable substances.

Animals↗

PubMed2004

Pax5-deficient mice exhibit early onset osteopenia with increased osteoclast progenitors.

Pax5 encodes BSAP, a member of the paired box domain transcription factors, whose expression is restricted to B lymphocyte lineage cells. Pax5(-/-) mice have a developmental arrest of the B cell lineage at the pro-B cell stage. We show here that Pax5(-/-) mice are severely osteopenic, missing 60% of their bone mass. The osteopenia can be accounted for by a >100% increase in the number of osteoclasts in bone measured histomorphometrically. This is not due to a lack of B cells, because other strains of B cell-deficient mice do not exhibit this phenotype. There was no difference in the number of osteoclasts produced in vitro by wild-type and Pax5(-/-) bone marrow cells. In contrast, spleen cells from Pax5(-/-) mice produce as much as five times the number of osteoclasts as control spleen cells. Culture of Pax5(-/-) spleen cells yields a population of adherent cells that grow spontaneously in culture without added growth factors for >4 wk. These cells have a monocyte phenotype, produce large numbers of osteoclasts when induced in vitro, and therefore are highly enriched in osteoclast precursors. These data demonstrate a previously unsuspected connection between B cell and osteoclast development and a key role for Pax5 in the control of osteoclast development.

Animals↗

PubMed2000

Effects of continuous calcitonin treatment on osteoclasts derived from cocultures of mouse marrow stromal and spleen cells.

BACKGROUND: Continuous calcitonin (CT) treatment for bone diseases associated with increased bone resorption may be followed by prolonged depression of osteoclast response to CT. The mechanisms of this "escape" phenomenon remain unclear. METHODS: We examined the effects of continuous CT treatment on cell formation, calcitonin receptor (CTR) expression, response to CT, and bone resorption of osteoclasts in a coculture of mouse marrow stromal and spleen cells in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Cells were cocultured and treated with salmon CT (sCT) for 7, 14, or 21 days. The effects of continuous CT treatment on osteoclast formation was determined by quantitation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs). CTR expression in osteoclasts was determined by binding of [125I]sCT in autoradiography. Bone resorption and CT responsiveness were assessed by examining the formation of resorption pits and by enumerating osteoclast reattachment on dentine slices after sCT rechallenge. RESULTS: TRAP-positive MNCs appeared in cocultures treated with sCT and were similar in number and morphology to those in control cultures, regardless of the concentration and duration of sCT treatment. A decrease in CTR expression was identified as a loss of silver grains from the TRAP-positive cells in cocultures receiving sCT treatment for 14 or 21 days. Partial recovery of CTR expression in TRAP-positive cells was evident in cocultures treated with sCT for only the first 7 days of coculture. TRAP-positive MNCs in cocultures treated with sCT for 14 or 21 days were resistant to the rechallenge with sCT. They attached to dentine slices and caused numerous resorption pits compared with control cells and cells treated with sCT for the first 7 days of coculture (p < 0.01). CONCLUSION: These findings suggest that the escape phenomenon that develops after continuous CT treatment may be due, at least in part to: 1) loss of responsiveness to CT in existing osteoclasts; and 2) development of new osteoclasts that are CTR-deficient and, therefore, refractory to CT rechallenge.

Animals↗

PubMed2001

Porphyromonas gingivalis lipopolysaccharide activated bone resorption of osteoclasts by inducing IL-1, TNF, and PGE.

AIM: To study the effects of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on inducing interleukin-1 (IL-1), tumor necrosis factor (TNF), prostaglandin E (PGE), and activating osteoclasts, in order to understand mechanism of osteoclast activation. METHODS: Pg-LPS was prepared by phenol-water method. IL-1, TNF, and PGE induced by Pg-LPS were isolated by chromatography. Ca2+ concentration was detected by atomic absorption spectrophotometry. Acid phosphatase and carbonic anhydrase in periodontal membranes were examined by histochemistry. RESULTS: Pg-LPS was able to stimulate peripheral blood mononuclear cells (PBMC) or the cells from human periodontal tissue secreting IL-1, TNF, and PGE. The outputs of these cytokines were increased in pace with the enhancement of Pg-LPS at the dose range of 0.5 - 5.0 mg/L. All of the three cytokines showed activities of accelerating Ca2+ release from rat calvarial bones, and the activity of PGE was the strongest. The amounts of both the acid phosphatase and carbonic anhydrase in the periodontal membranes of Pg-LPS injected rats were obviously increased (P < 0.01). In the periodontal membranes of Pg-LPS injected rats, the amount of activated osteoclasts were obviously increased in pace with Pg-LPS injection times (P < 0.01). However, the activating rates of osteoclasts were stable to approximately 65 % because of the increase of inactivated osteoclasts. CONCLUSION: Pg-LPS possessed strong activities to induce human PBMC and the cells from human periodontal tissue to produce IL-1, TNF, and PGE in a dose-dependent m anner within a certain concentration range of the LPS. Pg-LPS could efficiently activate osteoclasts, and the mechanism of osteoclast activation was probably associated with the increase of acid phosphatase and carbonic anhydrase.

Alprostadil↗

PubMedDate not supplied

In vitro osteoclast resorption of bone substitute biomaterials used for implant site augmentation: a pilot study.

PURPOSE: This observational study examined the resorptive behavior of normal neonatal rabbit osteoclasts grown on slices of bovine cortical bone as compared to samples of commercially available bone substitute biomaterials. It also examined the surface characteristics of these materials. MATERIALS AND METHODS: The 11 materials tested fell into 3 groups: (1) bone-derived, including freeze-dried human rib block, human demineralized freeze-dried bone, and deproteinated bovine bone; (2) synthetic hydroxyapatites (HA); and (3) synthetic non-HA, including coated methacrylates and coated silica glass. After 4 days in culture, 1 group of samples of each material underwent scanning electron microscopy (SEM) to evaluate resorptive pitting versus controls, while another group underwent tartrate-resistant acid phosphatase staining and light microscopy to examine osteoclast numbers and morphology. The 2 bovine-derived HA materials also underwent immunohistochemical staining and surface chemistry analysis. RESULTS: While most of these materials supported osteoclast attachment, some spreading, and survival in culture, only the bone-derived materials, with the exception of sintered deproteinated bovine bone, showed large scalloped-edged resorption pits with trails and exposed collagen when examined by SEM, although not to the same extent as unprocessed natural bone material. The HA materials and the sintered deproteinated bovine bone showed evidence of etching with smaller pits but no evidence of resorptive trail formation. The non-HA materials showed no evidence of pit formation or trails. Under immunohistochemical staining, Bio-Oss appeared to be positive for type I collagen after osteoclast activity on its surface, while Osteograf/N showed no positive staining. Surface chemistry analysis revealed nitrogen present in Bio-Oss specimens (0.17% to 0.47%), while there was no nitrogen detected in the Osteograf/N (0.00%); the percent nitrogen observed in normal bovine bone controls was 6.01% to 9.25%. DISCUSSION: The bone-derived materials supported osteoclast activity on the material surface in a way that facilitated formation of the more complex resorption pits in vitro. Assuming the rate of pit formation observed in vitro mimics that observed in vivo, the quantity and type of osteoclastic remodeling seen on non-bone-derived materials--and perhaps sintered bone-derived materials--would be extremely slow to negligible. Physiologic removal of non-bone-derived bone substitutes in vivo may occur by methods other than osteoclast resorption. CONCLUSIONS: Allogenous and xenogenous bone-derived materials that undergo delayed physiologic resorption may be more appropriately used with a staged surgical approach when used in sites intended to support osseointegrated dental implants. The combination of collagen staining and the presence of nitrogen suggest that there may be residual protein in Bio-Oss.

Acid Phosphatase↗

PubMed2003

[Possible mechanism of the specific action of bisphosphonates on osteoclasts].

The mechanism of action of bisphosphonates on bone resorption was examined in mouse culture systems. Tiludronate did not inhibit the formation of osteoclasts induced by 1,25-dihydroxyvitamin D3 in cocultures of osteoblasts and bone marrow cells. Osteoclasts obtained from cocultures treated with tiludronate formed many resorption pits on dentine slices. However, pit formation by osteoclasts was dose-dependently inhibited by tiludronate. Treatment of osteoclasts with risedronate disrupted actin rings, and inhibited pit formation by osteoclasts. Bafilomycin A1, a vacuolar H(+)-ATPase inhibitor, inhibited the pit-forming activity of osteoclasts but did not disrupt actin rings. Risedronate failed to disrupt actin rings in the presence of bafilomycin A1. These results suggest that acidification by vacuolar H(+)-ATPase is involved in specific incorporation of bisphosphonates into osteoclasts.

Animals↗