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PubMed1998

Interleukins in the control of osteoclast differentiation.

To maintain homeostasis of bone, the production of osteoblasts and osteoclasts is tightly regulated. At the local level, hormones and cytokines control formation of osteoclasts from hemopoietic precursors by acting upon osteoblastic-stromal cells and in some cases also upon cells of the immune system. Osteoblasts regulate osteoclast formation by providing physical support and cytokines such as M-CSF and IL-11, which promote osteoclast differentiation. Osteoblasts are also a source of IL-18, which limits osteoclast formation. The requirement of contact between osteoblasts and hemopoietic cells for successful osteoclast formation led to a concept of a membrane-anchored stromal cell molecule that programs osteoclast differentiation. This mechanism has been highlighted by the discovery of osteoprotegerin (OPG), a soluble tumor necrosis factor (TNF) family member that inhibits osteoclast formation. The ligand for OPG is a novel transmembrane TNF receptor superfamily member, the osteoclast differentiating factor (ODF). The recognition of the osteoprotegerin/osteoprotegerin-ligand axis will lead to new insights into the control of osteoclast differentiation by interleukins.

Animals↗
PubMed1998

Detection of estrogen receptor alpha, carbonic anhydrase II and tartrate-resistant acid phosphatase mRNAs in putative mononuclear osteoclast precursor cells of neonatal rats by fluorescence in situ hybridization.

Increasing evidence suggests that estrogen deficiency in women promotes the expansion of populations of bone marrow cells that differentiate into osteoclasts under the influence of osteotropic hormones and local factors. A progressive cytoplasmic accumulation of osteoclastic bone resorbing enzymes, such as tartrate-resistant acid phosphatase (TRACP) and carbonic anhydrase II (CA II), characterizes osteoclast differentiation. To evaluate the possibility that estrogen may have a direct effect on osteoclast precursor cells, we investigated the mRNA levels of estrogen receptor a (ERa), TRACP and CA II genes in neonatal rat bone imprints by fluorescence in situ hybridization and confocal microscopy. Morphological assessment of bone imprints has shown that the putative mononuclear osteoclast precursor cells (MOPC) display strongly basophilic cytoplasm and a low nuclear/cytoplasmic ratio, while some of these cells possess pale-staining ruffled border regions similar to those observed in osteoclasts. Both CA II and TRACP mRNAs were detected in putative MOPC as well as multinuclear osteoclasts. The gene transcripts were mainly located in the cytoplasm of these cells. To determine whether these putative MOPC possess ER mRNA, a 637 base pair antisense ER riboprobe was used. The results indicated that MOPC which show TRACP reactivity express high levels of ER gene transcripts in their cytoplasm. In contrast, only a few multinuclear osteoclasts in the bone imprints possessed ER gene transcripts. Interestingly, the levels of ER mRNA in these multinuclear osteoclasts were very low compared with those in the putative MOPC. Treatment with RNase prior to hybridization resulted in a significant loss of signal in these cells. The results of these studies suggest that estrogen may have a direct role in modulating the recruitment of osteoclast precursor cells during osteoclastogenesis.

Acid Phosphatase↗
PubMed2003

Nicotine stimulates osteoclast resorption in a porcine marrow cell model.

BACKGROUND: Combustible tobacco use is generally linked with accelerated periodontal bone loss and diminished post-surgical wound healing; however, the pathogenesis of this process at the cellular level remains unclear. Nicotine is known to affect human gingival fibroblast orientation, attachment, and beta1 integrin expression, yet little is known about its effects on osteoclasts, the cells most responsible for bone resorption. The purpose of this study was to determine the effects of physiologically relevant nicotine levels on porcine osteoclast function as measured by resorption of calcium phosphate. METHODS: Pure nicotine was diluted in medium to the following concentrations: 0.03 microM, 0.15 microM, 0.30 microM, 0.60 microM, and 1.50 microM. Porcine osteoclasts were seeded onto calcium phosphate multi-test slides and incubated at 37 degrees C with half media changes every 24 hours. Cells received 0, 0.15, 0.30, 0.60, and 1.50 microM nicotine, or 25 nM parathyroid hormone (PTH). Osteoclast resorption was quantified by measuring the resorbed surface area of the calcium phosphate substrate. RESULTS: Osteoclast cultures resorbed bone slices and calcium phosphate substrate. All nicotine concentrations and PTH resulted in statistically significantly greater mean percent resorptions than the control group (P < 0.05). However, no statistical difference was found between the various nicotine doses or PTH. The number of osteoclasts increased in a linear relationship to the increasing nicotine concentrations; however, no correlation was found between osteoclast number and the amount of resorption. CONCLUSIONS: Nicotine is non-toxic to osteoclasts at the clinically relevant levels tested. Nicotine appears to stimulate osteoclast differentiation and resorption of calcium phosphate, the major component of bone. Nicotine-modulated osteoclast stimulation may, in part, explain the increased rapidity of periodontal bone loss and refractory disease incidence in smokers.

Analysis of Variance↗
PubMed2005

Advances in osteoclast differentiation and function.

Osteoclasts are the sole bone resorbing cells. These cells are essential for skeletal development and remodeling throughout the life of animal and man. Deficiency of osteoclasts leads to osteopetrosis, a diseases manifested by increased non-remodeled bone mass, which ultimately leads to bone deformities and functional failure of other body systems. On the other hand, increased number and activity of osteoclasts under certain pathologic conditions causes accelerated bone resorption and may lead to osteoporosis and osteolytic diseases. To better understand the mechanisms underlying osteoclast-based diseases and design relevant therapies, one should unveil the molecular basis of osteoclast differentiation and function and regulatory mechanisms of osteoclast signaling. This review will outline up-to-date information regarding osteoclast differentiation and activation. Molecular mechanisms underlying osteoclast signaling pathways in inflammatory osteolysis and arthritis will be discussed. In addition, stimulators and inhibitors of osteoclasts, as well as current therapies for osteoclast activity will be addressed.

Animals↗
PubMed1999

Mechanism in inhibitory effects of vitamin K2 on osteoclastic bone resorption: in vivo study in osteopetrotic (op/op) mice.

Osteoclast deficiency in op/op mice was cured by a single injection of 5 micrograms recombinant human macrophage colony-stimulating factor (M-CSF). On d 5, the osteoclast number reached a maximum value. By d 15, the osteoclast number had decreased to about 70% of the maximum level. Moreover, by d 20, the osteoclast number had decreased to about 30% of its maximum level. On d 5, the osteoclast number of vitamin K2 12 h previously had decreased to about 30% of the M-CSF-only injected mice. Moreover, on d 5, the osteoclast number of the mice receiving a single injection of vitamin K2 24 h previously had decreased to about 15% that of mice injected only with M-CSF. These results indicate that vitamin K2 inhibits in vivo osteoclast formation. On d 20, the osteoclast number of the mice injected with a single dose of vitamin K2 12 or 24 h previously had decreased to 0% compared with those receiving only M-CSF. The present results suggest that the vitamin K2 "causes cell death" to mature osteoclasts and inhibits in vivo osteoclast formation.

Animals↗
PubMed2000

Suppressive effect of genistein on rat bone osteoclasts: involvement of protein kinase inhibition and protein tyrosine phosphatase activation.

The suppressive effect of genistein on osteoclast-like multinucleated cells from rat femoral tissues was investigated. The bone cells isolated from rat femoral tissues were cultured for 48 h in an alpha-minimal essential medium (5% fetal bovine serum) containing either vehicle or genistein (10(-7)-10(-5) M). Osteoclasts were estimated by staining for tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts. The presence of genistein caused a significant decrease in the number of osteoclasts. Such a decrease was also seen in the presence of calcium choride (10(-5) M). Magnesium chloride (10(-5)-10(-3) M), a blocker of Ca2+ channels, had no effect on the number of osteoclasts. The effect of genistein (10(-5) M) or calcium (10(-3) M) in decreasing osteoclasts was significantly prevented by the presence of magnesium (10-3 M). Vanadate (10(-6)-10(-4) M), an inhibitor of protein tyrosine phosphatase activity, did not have an effect on the number of osteoclasts. The genistein's effect was not altered by vanadate. When isolated osteoclasts were cultured for 24 h in the presence of genistein (10(-7)-10(-5) M), protein kinase activity in the 5500 g supernatant of homogenate of the cells was significantly decreased, while protein tyrosine phosphatase activity was significantly elevated. Such an effect was also seen by the addition of genistein (10(-7)-10(-5) in the enzyme reaction mixture in vitro. The present study suggests that the suppressive effect of genistein on rat bone osteoclasts is partly involved in the inhibition of protein kinase and the activation of protein tyrosine phosphatase in osteoclasts.

Animals↗
PubMed2002

Stimulation by toll-like receptors inhibits osteoclast differentiation.

Osteoclasts, the cells capable of resorbing bone, are derived from hemopoietic precursor cells of monocyte-macrophage lineage. The same precursor cells can also give rise to macrophages and dendritic cells, which are essential for proper immune responses to various pathogens. Immune responses to microbial pathogens are often triggered because various microbial components induce the maturation and activation of immunoregulatory cells such as macrophages or dendritic cells by stimulating Toll-like receptors (TLRs). Since osteoclasts arise from the same precursors as macrophages, we tested whether TLRs play any role during osteoclast differentiation. We showed here that osteoclast precursors prepared from mouse bone marrow cells expressed all known murine TLRs (TLR1-TLR9). Moreover, various TLR ligands (e.g., peptidoglycan, poly(I:C) dsRNA, LPS, and CpG motif of unmethylated DNA, which act as ligands for TLR2, 3, 4, and 9, respectively) induced NF-kappa B activation and up-regulated TNF-alpha production in osteoclast precursor cells. Unexpectedly, however, TLR stimulation of osteoclast precursors by these microbial products strongly inhibited their differentiation into multinucleated, mature osteoclasts induced by TNF-related activation-induced cytokine. Rather, TLR stimulation maintained the phagocytic activity of osteoclast precursors in the presence of osteoclastogenic stimuli M-CSF and TNF-related activation-induced cytokine. Taken together, these results suggest that TLR stimulation of osteoclast precursors inhibits their differentiation into noninflammatory mature osteoclasts during microbial infection. This process favors immune responses and may be critical to prevent pathogenic effects of microbial invasion on bone.

Animals↗
PubMed2003

Total coumarins from fruits of Cnidium monnieri inhibit formation and differentiation of multinucleated osteoclasts of rats.

AIM: To determine the effects of TCFC (total comarins from the fruits of Cnidium monnieri) on the activity of osteoclasts in vitro. METHODS: Osteoclasts isolated from rat marrow cells were co-cultured with osteoblasts under the 1,25-dihydroxyvitamine D3. The tartrate-resistant acid phosphatase (TRAP) stain was used to identify osteoclast morphology. The activity of TRAP was measured by p-nitrophenyl sodium phosphate assay. The resorption pit area on the bone slices formed by osteoclasts was measured by computer image processing. Calcium concentration in the medium of co-culture of bone slices and osteoclasts was determined by atomic absorption spectra. RESULTS: TCFC 2.5-25 mg/L inhibited osteoclast formation and differentiation. TCFC 0.25-25 mg/L inhibited TRAP activity of osteoclasts and TCFC 25 mg/L decreased the TRAP activity by 26.3 % and 24.1 % after 48 h and 72 h, respectively. TCFC 25 mg/L decreased the osteoclastic bone resorption pit area by 25.05 % and Ca2+ release from bone slices by 41.73 %. CONCLUSION: TCFC reduced the bone lose by decreasing the osteoclast formation, its TRAP activity, and osteoclastic bone resorption.

Acid Phosphatase↗
PubMed1987

Direct and indirect radiation effects on osteoclast formation in vitro.

An in vitro co-culture system was applied to study the direct and indirect effects of irradiation on osteoclast formation. Osteoclast precursor-free fetal mouse metatarsal bones were employed as osteoclast-forming inductor and periostea dissected from fetal calvaria as source of proliferating progenitor cells. Direct radiation effects on the formation of osteoclasts were assessed in co-cultures of irradiated periostea and non-irradiated bone rudiments. The results showed that the (blood-borne) periosteal progenitors were rather radiosensitive. A radiation 'survival' curve of osteoclast formation in relation to various doses could be constructed yielding a mean lethal dose (Do value) of 0.94 +/- 0.02 Gy and an extrapolation number of 1.67 +/- 0.01. Irradiation of the fetal long bones by low doses, effective for direct elimination of osteoclast progenitor cells, did not indirectly affect osteoclast development from the non-irradiated periosteal progenitor population. However, at relatively high radiation levels, though not lethal for the long bone rudiments, a significant inhibition of osteoclast formation became evident. The results indicate that radiation primarily affects osteoclast formation via a direct action on radiosensitive, proliferating progenitor cells. Injury to long bone models by relatively high radiation doses may also lead to severe disturbance of osteoclast formation kinetics.

Acid Phosphatase↗
PubMed1987

Comparison of direct and indirect radiation effects on osteoclast formation from progenitor cells derived from different hemopoietic sources.

Hemopoietic stem and progenitor cells from different sources differ in radiosensitivity. Recently, we have demonstrated that the multinucleated cell responsible for bone resorption and marrow cavity formation, the osteoclast, is in fact of hemopoietic lineage. In this investigation we have studied the radiosensitivity of osteoclast formation from two different hemopoietic tissues: fetal liver and adult bone marrow. Development of osteoclasts from hemopoietic progenitors was induced by coculture of hemopoietic cell populations with fetal mouse long bones depleted of their own osteoclast precursor pool. During culture, osteoclasts developed from the exogenous cell population and invaded the calcified hypertrophic cartilage of the long bone model, thereby giving rise to the formation of a primitive marrow cavity. To analyze the radiosensitivity of osteoclast formation, either the hemopoietic cells or the bone rudiments were irradiated before coculture. Fetal liver cells were found to be less radiosensitive than bone marrow cells. The D0, Dq values and extrapolation numbers were 1.69 Gy, 5.30 Gy, and 24.40 for fetal liver cells and 1.01 Gy, 1.85 Gy, and 6.02 for bone marrow cells. Irradiation of the (pre)osteoclast-free long bone rudiments instead of the hemopoietic sources resulted in a significant inhibition of osteoclast formation at doses of 4 Gy or more. This indirect effect appeared to be more prominent in the cocultures with fetal than with adult hemopoietic cells. Furthermore, radiation doses of 8.0-10.0 Gy indirectly affected the appearance of other cell types (e.g., granulocytes) in the newly formed but underdeveloped marrow cavity. The results indicate that osteoclast progenitors from different hemopoietic sources exhibit a distinct sensitivity to ionizing irradiation. Radiation injury to long bone rudiments disturbs the osteoclast-forming capacity as well as the hemopoietic microenvironment.

Animals↗
PubMed1981

Osteoclast formation in response to intraperitoneal injection of 1 alpha-hydroxycholecalciferol in mice.

In order to assess osteoclast formation in response to 1 alpha-hydroxycholecalciferol, osteoclast counts per cm of bone surface were performed on paraffin sections of femurs of male CBA mice killed at daily intervals up to 5 days. All animals received daily intraperitoneal injections of 1 alpha-hydroxycholecalciferol up to the time of death. Peak osteoclast formation occurred during the third day, by the end of which maximum numbers of osteoclasts were achieved (11.9 +/- 0.9 osteoclast cm-1) compared to controls (3.5 +/- 0.6 osteoclast cm-1), this increase being highly significant (p less than 0.01). Although the osteoclast population was most dense at the metaphyseal plate in both experimental and control groups, osteoclast counts in this region only doubled whereas overall osteoclast counts more than tripled. The number of nuclei per osteoclast did not significantly alter following four daily injections of 1 alpha-hydroxycholecalciferol.

Animals↗
PubMed1981

Kinetics of osteoclasts and their nuclei in evolving secondary Haversian systems.

A study of osteoclast and osteoclast nuclear population kinetics within evolving secondary osteons was undertaken in young adult Beagle dogs. Autoradiographs of serial longitudinal rib biopsy sections taken from 1 hour to 15 days after tritiated thymidine injection were analysed as to the time and the rate of appearance of the labelled nuclei within the osteoclasts and their nuclei. Such systems contained an average of nine osteoclasts, each containing an average of nine nuclei. Labelled osteoclast nuclei first appeared within 24 hours, peaked at 10% at 4 days, and declined to 1% or less after 11.5 days more. Thus, the entry rate of new nuclei into (and their exit from) the population of osteoclast nuclei under steady state conditions approximates 8% per day. Therefore, the total mononuclear osteoclast population may be viewed as divided into functional units, i.e. osteoclasts. From the ratio of the osteoclast nuclei in the cutting cone to the number of osteoblasts in the closing cone (as well as from their rates of resorption and formation), it was deduced that the osteoclast per nucleus is approximately 20-40 times more efficient than the osteoblast. Because of the intrinsically different efficiencies and life spans of these two cell types, the rates of resorption and formation within evolving Haversian systems and the amounts of bone ultimately resorbed and formed by the system, are determined by the rate and duration of the respective precursor cell proliferation. It is at this level that factors which control the bone remodelling and balance must operate.

Animals↗
PubMed1994

[Osteoclasts and tartrate-resistant acid phosphatase-positive mononuclear cells in the mouse femur: a histochemical study].

Osteoclasts contain tartrate-resistant acid phosphatase (TRAP). To understand the role of osteoclasts in trabecular bone formation, the distal spongiosa of the femurs from 1, 2, 4, 8, 16, and 24 week-old mice were histochemically examined in methacrylate sections stained with an azo-dye method for TRAP. For quantitative evaluations, the surface density of trabecular bones, length of the spongy bones, numerical density of TRAP-positive cells (osteoclasts and mononuclear cells), proportions of the trabecular bone surface covered with osteoclasts, numerical density of osteoclasts on the trabecular bone surface, size of osteoclasts, and distribution of TRAP-positive mononuclear cells in the bone marrow were examined. In conclusion, the results indicate that 1) in the spongiosa, osteoclasts are distributed numerously at the ossification front along the epiphyseal cartilage, junction between the primary and secondary spongiosas, and diaphyseal end of trabecular bones for modeling of the spongiosa, 2) osteoclasts function independently from osteoblasts at the ossification front and the diaphyseal end of trabecular bones, 3) spongiosa changes the amount of trabecular bones through the bone formation-resorption equivalent stage, bone formation dominant stage, and bone resorption dominant stage, 4) TRAP-positive mononuclear cells, probable preosteoclasts, are distributed in the bone marrow, and 5) TRAP-positive mononuclear cells appear frequently in the marrow around osteoclasts, suggesting that osteoclast activity produces a differentiation or migration factor for preosteoclasts.

Acid Phosphatase↗
PubMed1993

The occurrence of mitochondrial variations including large mitochondria in osteoclasts following calcitonin treatment.

Calcitonin-treated osteoclasts with mitochondrial variations, including large mitochondria, and osteoclasts not treated with calcitonin (control osteoclasts) were examined using cytochrome c oxidase activity and morphological analysis of mitochondria. The calcitonin-treated osteoclasts were divided into two types. One was osteoclasts with only a clear zone, which contained many type 1 mitochondria with the reaction products of cytochrome c oxidase in both the inner membrane of the cristae and the outer compartment in the vascular side and a comparatively small number of type 1 mitochondria in the resorptive side. The other type was osteoclasts with a mature ruffled border, in which many type 1 mitochondria were observed in both sides. Most of the large mitochondria were type 1, and these were observed only in the vascular side of the osteoclasts with only a clear zone, and in both sides of the osteoclasts with a mature ruffled border. In statistical analysis, the cross-sectional area of mitochondria in the vascular side of calcitonin-treated osteoclasts was larger than that of those in the resorptive side, and the numerical percentage of type 1 mitochondria in the vascular side was greater than that in the resorptive side. In contrast, the cross-sectional area of mitochondria in the vascular side of control osteoclasts was smaller than that in the resorptive side, and there was no significant difference between the two groups in the numerical percentage of type 1 mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Osteoclast differentiation antigen.

Osteoclasts are the primary cells which perform bone resorption. The origin of these multinucleated giant cells is the haematopoietic stem cells. The differentiation pathway of the osteoclasts has so far been well studied and the cell-lineage of these bone resorbing cells is considered to be close but not identical to the monocytes/macrophages. Owing to the development of in vitro culture systems for evaluating osteoclast differentiation, it has been elucidated that various cytokines are involved in the differentiation of the osteoclasts. However, there is still ambiguity concerning the molecular mechanism of the differentiation of the osteoclasts. One approach for clarifying the molecular mechanism is to find unique antigen molecules involved in the process of osteoclast differentiation. In this review article, we introduce such immunological studies concerning osteoclast differentiation. We also refer to our recent establishment of a panel of monoclonal antibodies recognizing rat osteoclasts. One of the monoclonal antibodies recognizes cell surface antigen (Kat1-antigen) expressed on cells in osteoclast-lineage and not on monocytes/macrophages. Cross-linking of the cell surface antigen using this monoclonal antibody showed that the Kat1-antigen is the unique cell surface molecule involved in the regulation of the affinity of the calcitonin receptor and also involved in the modulation of bone resorption. In this review article, we overview, the current issues which should be elucidated for understanding the differentiation and activation of the osteoclasts. We further emphasize the utility of the immunological approach for solving these current target issues.

Animals↗
PubMed2001

Connexin-mimetic peptide Gap 27 decreases osteoclastic activity.

BACKGROUND: Bone remodelling is dependent on the balance between bone resorbing osteoclasts and bone forming osteoblasts. We have shown previously that osteoclasts contain gap-junctional protein connexin-43 and that a commonly used gap-junctional inhibitor, heptanol, can inhibit osteoclastic bone resorption. Since heptanol may also have some unspecific effect unrelated to gap-junctional inhibition we wanted to test the importance of gap-junctional communication to osteoclasts using a more specific inhibitor. METHODS: A synthetic connexin-mimetic peptide, Gap 27, was used to evaluate the contribution of gap-junctional communication to osteoclastic bone resorption. We utilised the well-characterised pit-formation assay to study the effects of the specific gap-junctional inhibitor to the survival and activity of osteoclasts. RESULTS: Gap 27 caused a remarked decrease in the number of both TRAP-positive mononuclear and multinucleated rat osteoclasts cultured on bovine bone slices. The decrease in the cell survival seemed to be restricted to TRAP-positive cells, whereas the other cells of the culture model seemed unaffected. The activity of the remaining osteoclasts was found to be diminished by measuring the percentage of osteoclasts with actin rings of all TRAP-positive cells. In addition, the resorbed area in the treated cultures was greatly diminished. CONCLUSIONS: On the basis of these results we conclude that gap-junctional communication is essential for the action of bone resorbing osteoclasts and for proper remodelling for bone.

Journal Article↗
PubMed2003

Estrogen regulates the production of VEGF for osteoclast formation and activity in op/op mice.

UNLABELLED: Op/op mice have a severe deficiency of osteoclasts because of lacking functional M-CSF that is an essential factor of osteoclast differentiation and function. We now report that OVX induces osteoclast formation and cures osteopetrosis by increasing the VEGF that regulates osteoclast formation in these mice. INTRODUCTION: We have found that estrogen deficiency induced by ovariectomy (OVX) upregulated osteoclast formation in op/op mice. We have recently demonstrated that vascular endothelial growth factor (VEGF) could substitute for macrophage colony-stimulating factor (M-CSF) in the support of osteoclastic bone resorption in these mice. Therefore, in this study, we wished to assess the effects of VEGF on bone loss induced by OVX in these mice. MATERIALS AND METHODS: Eight-week-old op/op mice were bilateral OVX or sham-operated. Mice were killed at 8, 10, and 12 weeks of age, and femurs were removed for preparations. Some OVX mice were treated with three consecutive injections of 120 microl/body of VEGF-neutralizing antibody at 12-h intervals starting from 36 h before death at 4 weeks after OVX. VEGFR-1/Fc chimeric protein (600 microg/kg/day) or 17beta-estradiol (0.16 microg/day) was administered in a dorsal subcutaneous pocket of the mice at the time of OVX. These mice were killed 2 weeks after surgery. Changes of serum levels of VEGF were measured by ELISA. Changes of mRNA levels of VEGF, Flt-1, interleukin-6, and osteoclast differentiation factor (ODF/TRANCE/RANKL) in bone tissue were measured by reverse transcriptase-polymerase chain reaction. RESULTS: In OVX op/op mice, trabecular bone volume of the femur was decreased, and the number of osteoclasts was significantly increased. Serum levels of VEGF were demonstrated to be higher in OVX mice than in sham-operated mice. VEGF mRNA, Flt-1 mRNA, interleukin-6 mRNA, and RANKL mRNA levels in bone tissue were elevated in OVX mice over that in sham-operated mice. The increase in osteoclast number was inhibited by VEGF antagonist treatment in OVX mice. CONCLUSIONS: In this study, we have demonstrated that the production of VEGF and RANKL stimulated by OVX results in increased osteoclast formation in op/op mice.

Animals↗
PubMed1997

Osteoclast precursors in bone marrow and peritoneal cavity.

Osteoclasts differentiate from cells that share some phenotypes with mature macrophages and monocytes, but early precursors for osteoclasts still remain obscure. To characterize osteoclast precursors, using monoclonal anti-c-Fms and anti-c-Kit antibodies, bone marrow cells were separated and the frequency of clonogenic progenitors were measured. Osteoclast precursors in the bone marrow mainly expressed c-Kit and diminished in frequency when they expressed c-Fms. In contrast to bone marrow, the precursors in the peritoneal cavity were enriched with a population of c-Fms+. Injection of these antibodies into mice demonstrated that peritoneal osteoclast precursors were sensitive to anti-c-Fms but not to anti-c-Kit antibodies, whereas those in bone marrow only declined in the presence of both antibodies. Meanwhile, c-Fms as opposed to c-Kit played an essential role in the generation of osteoclasts in cultures. We also compared osteoclast precursors with colony forming cells (CFU-M) by a macrophage colony stimulating factor. CFU-M in bone marrow decreased when anti-c-Kit antibody was administered and no CFU-M was detected in peritoneum. In this study, we show differences between proliferative potential osteoclast precursors maintained in bone marrow and peritoneum and between CFU-M and osteoclast precursors.

Animals↗