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PubMed1994

Interleukin-6 does not mediate the stimulation by prostaglandin E2, parathyroid hormone, or 1,25 dihydroxyvitamin D3 of osteoclast differentiation and bone resorption in neonatal mouse parietal bones.

The cytokine interleukin-6 (IL-6) was produced by neonatal mouse parietal bones during a 6- or 48-hour culture period in response to prostaglandin E2 (PGE2) and bovine parathyroid hormone (PTH) 1-34 fragment but not 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. At the same time there was an increase in tartrate-resistant, acid phosphatase-positive osteoclasts (TRAP+OC) with all three osteotropic effectors over 6 hours, and an increase in 45Ca release over 48 hours. TRAP+OC numbers on PGE2-stimulated bones were positively correlated with IL-6 concentration. Our aim was to determine if IL-6 mediated this response. Recombinant human IL-6 (rhIL-6) was added to parietal bones in culture at concentrations within the range that PGE2 or PTH would produce during incubation. However, over 6 or 48 hours, rhIL-6 did not stimulate TRAP+OC to increase in number nor did it cause an increase in calcium release over 48 hours. Adding an antibody against mouse IL-6 to bone cultures stimulated with PTH or PGE2 neutralized the resulting IL-6 bioactivity by up to 92% but did not inhibit TRAP+OC formation. We conclude that although IL-6 is produced in response to two important stimulators of bone resorption, it does not mediate osteoclast differentiation or bone resorption in this model.

Acid Phosphatase↗
PubMed2003

[Therapeutic approaches to increased bone resorption].

The accelerated bone resorption contributes significantly to the pathophysiology of diseases such as osteoporosis, Paget's disease, hypercalcemia, bone metastasis, and inflammation of bone associated with rheumatoid arthritis. Several antiresorptive agents have been validated as a means to control bone resorption in these diseases. A recent understanding of the molecular mechanism of osteoclastic bone resorption is providing opportunities for developing novel antiresorptive agents.

English Abstract↗
PubMed2004

The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation.

UNLABELLED: Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone formation. This study indicates that chloride channel inhibitors are highly promising for treatment of osteoporosis. INTRODUCTION: The chloride channel inhibitor, NS3736, blocked osteoclastic acidification and resorption in vitro with an IC50 value of 30 microM. When tested in the rat ovariectomy model for osteoporosis, daily treatment with 30 mg/kg orally protected bone strength and BMD by approximately 50% 6 weeks after surgery. Most interestingly, bone formation assessed by osteocalcin, mineral apposition rate, and mineralized surface index was not inhibited. MATERIALS AND METHODS: Analysis of chloride channels in human osteoclasts revealed that ClC-7 and CLIC1 were highly expressed. Furthermore, by electrophysiology, we detected a volume-activated anion channel on human osteoclasts. Screening 50 different human tissues showed a broad expression for CLIC1 and a restricted immunoreactivity for ClC-7, appearing mainly in osteoclasts, ovaries, appendix, and Purkinje cells. This highly selective distribution predicts that inhibition of ClC-7 should specifically target osteoclasts in vivo. We suggest that NS3736 is inhibiting ClC-7, leading to a bone-specific effect in vivo. RESULTS AND CONCLUSION: In conclusion, we show for the first time that chloride channel inhibitors can be used for prevention of ovariectomy-induced bone loss without impeding bone formation. We speculate that the coupling of bone resorption to bone formation is linked to the acidification of the resorption lacunae, thereby enabling compounds that directly interfere with this process to be able to positive uncouple this process resulting in a net bone gain.

Animals↗
PubMed1995

Evidence for interrupted bone resorption in human iliac cancellous bone.

Bone resorption and formation are coupled both in time and space and may occur simultaneously in the same remodeling unit. A number of studies have shown that the formative phase of the remodeling sequence may undergo temporary interruptions prior to completion and it is possible that bone resorption may be subject to similar interruptions. We have investigated this hypothesis by studying the distribution of eroded depth in resorption cavities in human cancellous bone. Eroded depth was assessed in iliac crest cancellous bone from 41 normal healthy subjects using a cubic spline curve fitting technique. The distribution of mean eroded depths was skewed to the right. Comparison of the observed distribution with an expected distribution, which was calculated from previously published data and assumes resorption begins rapidly and slows as it approaches completion, showed a significantly greater proportion of shallower cavities than expected (p<0001). Similarly, comparison of observed and uniform distributions, which assumes a constant rate of resorption throughout the erosion period, also showed a significantly greater proportion of smaller cavities (p<0.01). In subjects aged less than 39 years, there were fewer small cavities than in those aged 40-59 years. In addition, there was some evidence that females of 40-59 years had a proportionately greater number of smaller cavities than males; however, there were no differences in other age groups. Our results demonstrate a significantly greater proportion of smaller resorption cavities than would be expected from current models of bone remodeling and are consistent with the hypothesis that resorption undergoes temporary interruptions and/or permanent arrest during the process of bone remodeling.

Adult↗
PubMed1996

Insulin-like growth factor I does not stimulate bone resorption in cultured neonatal mouse calvarial bones.

Insulin-like growth factor I (IGF-I) has documented anabolic effects on osteoblasts, whereas its influence on osteoclasts and on bone resorption is unclear. We have investigated the effects of IGF-I on osteoclast recruitment and bone resorption in vitro. IGF-I (at and above 1 nM) stimulated the formation of multinucleated tartrate-resistant acid phosphatase positive cells in murine bone marrow cultures, incubated for 9 days. The number of multinucleated cells increased to 540 +/- 160% of control (mean +/- SEM) in cultures treated with 10 nM IGF-I. IGF-I (0.1-100 nM) had no effect by itself on 45Ca-release from prelabelled neonatal mouse calvarial bones. However, IGF-I (100 nM) had an inhibitory effect on bone resorption induced by prostaglandin E2 and 1,25(OH)2D3. These findings indicate that IGF-I enhances the formation of osteoclasts-like cells in long-term bone marrow cultures. In bone organ cultures, however, IGF-I has an inhibitory effect on stimulated bone resorption, suggesting that IGF-I inhibits existing osteoclasts and, alternatively, that IGF-I interferes with the osteoblast-derived factor(s) that stimulate existing osteoclasts.

Animals↗
PubMed2005

Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption.

Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteoclast survival is increased when acidification is impaired, and that impairment of acidification results in inhibition of bone resorption without inhibition of bone formation. We investigated the role of acidification in human osteoclastic resorption and life span in vitro using inhibitors of chloride channels (NS5818/NS3696), the proton pump (bafilomycin) and cathepsin K. We found that bafilomycin and NS5818 dose dependently inhibited acidification of the osteoclastic resorption compartment and bone resorption. Inhibition of bone resorption by inhibition of acidification, but not cathepsin K inhibition, augmented osteoclast survival, which resulted in a 150 to 300% increase in osteoclasts compared to controls. We investigated the effect of inhibition of osteoclastic acidification in vivo by using the rat ovariectomy model with twice daily oral dosing of NS3696 at 50 mg/kg for 6 weeks. We observed a 60% decrease in resorption (DPYR), increased tartrate-resistant acid phosphatase levels, and no effect on bone formation evaluated by osteocalcin. We speculate that attenuated acidification inhibits dissolution of the inorganic phase of bone and results in an increased number of nonresorbing osteoclasts that are responsible for the coupling to normal bone formation. Thus, we suggest that acidification is essential for normal bone remodeling and that attenuated acidification leads to uncoupling with decreased bone resorption and unaffected bone formation.

Acid Phosphatase↗
PubMed1980

Direct measurement of bone resorption and calcium conservation during vitamin D deficiency or hypervitaminosis D.

When bone is remodeled during the growth of a given size bone to a larger size, some bone is resorbed and some is deposited. Much of the resorbed bone mineral, calcium, can be reutilized during bone formation. The net and absolute effects of normal growth, vitamin D deficiency, or vitamin D excess were compared on bone resorption, bone formation, and calcium reutilization. Growing chicks were prelabeled extensively with three isotopes: (45)Ca, [(3)H]tetracycline, and [(3)H]proline. Data were obtained weekly during 3 weeks of control growth, vitamin D deficiency, or vitamin D overdosage while on a nonradioactive diet. Bone resorption as measured by increases in the marrow (inner) diameter of the midshaft of the femur and humerus and by the weekly losses of total [(3)H]tetracycline and [(3)H]collagen per whole bone was not significantly different among any of the groups studied. The data indicated that the high rate of cortical bone resorption in experimental chicks was not increased above that observed in experimental chicks was not increased above that observed in control chicks. Vitamin D deficiency had little effect on the total (45)Ca in whole bones, whereas vitamin D-treated chicks lost 40% of their (45)Ca. Thus, vitamin D overdosage resulted in a decrease of (45)Ca reutilization, whereas vitamin D deficiency resulted in an apparent increase of (45)Ca reutilization. Both vitamin D-deficient and vitamin D-treated chicks had a decreased accumulation of dietary calcium per whole bone. The insufficient mineral mass in vitamin D-deficient chicks resulted from the indirect inhibition of bone mineralization due to the low intestinal absorption of calcium rather than from a change in bone resorption. In vitamin D-treated chicks the apparent bone atrophy and net loss of (45)Ca from bone resulted from inhibiting bone matrix formation and mineralization instead of increasing bone resorption. The constancy of bone resorption under these experimental conditions suggests that bone mineralization is the major regulator of bone mass.

Animals↗
PubMed1993

Importance of bone resorption in the determination of bone density in women more than 10 years past the menopause.

There is general agreement that bone density falls with age and is higher in heavy people than light people. We have studied a variety of potential correlates of vertebral, ankle, and hip bone density to evaluate other potential influences on the skeleton. We recruited 196 healthy women who were more than 10 years past the menopause and collected a diet and activity record, a 24 h urine, and a fasting blood and urine specimen. These blood and urine samples were analyzed for factors related to calcium homeostasis. We then measured bone density at lumbar vertebrae 1-4 and the hip and the ankle bone density of the nondominant leg. Correlations between vertebral, hip, and ankle bone density and other measured variables were explored using the statistical package SPSS PC. At the vertebral site, in addition to correlations with age and body mass index (BMI), a negative correlation with a measure of bone resorption, the hydroxyproline creatinine ratio (OHPCR), was noted. At the ankle site, in addition to correlation with age, BMI, and OHPCR, a positive correlation with activity and a negative correlation with serum calcitriol were noted. At the hip site, as well as age, BMI, and OHPCR, significant correlations with GFR and dietary calcium intake were noted. These data suggest that even in women 10 years past the menopause bone resorption has a significant effect on bone density, that renal function may account for some of the variance in bone density at the hip, and that activity effects are more marked at sites of greater loading, namely the ankle.

Aged↗
PubMed1982

Indomethacin inhibits bone resorption in vitro without affecting bone collagen synthesis.

The effect of indomethacin on the synthesis of collagen, non-collagen proteins and on bone resorption was studied in a bone organ culture system, using calvarial bones from 6-day-old mice. It was found that indomethacin reduced the release of calcium, inorganic phosphate and hydroxyproline without affecting the total amount of hydroxyproline in the cultures. Indomethacin had no effect on the synthesis of non-collagen proteins as estimated by the uptake of 3H-tryptophan. The inhibition of the release of hydroxyproline and minerals could be seen in concentrations of indomethacin from 10(-5) to 10(-8) M. Prostaglandin E2 (10(-7) M) could prevent the blocking capacity of indomethacin (10(-6) M), suggesting that the inhibitory action of the drug was due to the inhibition of endogenous prostaglandin synthesis. The results presented are compatible with the concept that indomethacin causes the reported detrimental skeletal effects by means of reduced osteoclastic rather than by reduced osteoblastic activity.

Animals↗
PubMed1996

Sex differences in absolute rates of bone resorption in young rats: appendicular versus axial bones.

This study compares absolute rates of bone resorption and formation at the organ level in adolescent Sprague-Dawley rats as a function of sex and type of bone. Bone resorption and formation were quantified in rapidly growing male and female rats (4-7 weeks of age) who were multiply prelabeled with [3H]tetracycline. Ten different whole bones were compared: four cranial or appendicular bones and six axial bones. Absolure rate of bone resorption was measured isotopically by the loss of 3H-tetracycline from each whole bone. Bone growth was quantified in terms of relative and absolute increase in bone calcium mass. When the rates of bone resorption (loss of [3H]-tetracycline as percent of whole bone per 3 weeks) were compared between sexes, the six axial bones showed significantly higher rates (P < 0.05-0.001) in males (64-73) than in females (37-66). No significant sex differences were observed in rate for the two cranial and two appendicular bones. During 4-7 weeks of age, a comparison of bone masses showed that only one bone (calvaria) gained more mass in the male and two bones (mandible and humerus) gained more mass in the female. In contrast, five of six axial bones gained more mass in the female. Thus, 7 out of 10 bones were larger in the female. In growing male and female rats, an inverse relationship appears between rate of bone resorption and mass for most of the axial bones; this relationship was not apparent for cranial or appendicular bones. Sexual dimorphism was consistently seen by greater axial bone mass in females. However, greater rates of bone resorption were seen in male axial bones but not in cranial or appendicular bones. It is apparent that the different types of bones are heterogeneous in their rates of resorption and formation during this period of growth.

Animals↗
PubMed1996

Inhibitory effects of bisphosphonate (YM175) on bone resorption induced by a metastatic bone tumor.

The effects of a third-generation bisphosphonate, YM175 (disodium dihydrogen (cycloheptylamino)-methylene-1,1-bisphosphonate), on bone resorption induced by a metastatic human melanoma cell line (A375) were investigated morphologically using an experimental model of bone metastases in nude mice. An injection of A375 in the left cardiac ventricle produced multiple osteolytic lesions. Then, 4 weeks after the cell injection, we administrated YM175 (1 mg/kg) intravenously once and sacrificed the animals 3 days later. On histochemical observation, there was a layer of stromal cells with numerous mononuclear and multinucleated tartrate-resistant acid phosphatase (TRAPase)-positive cells in the untreated control group. In contrast, this layer was extensively reduced in most areas, and only a few TRAPase-positive cells were seen around tumor nests and on the bone surface in the experimental group. Most of the TRAPase-positive cells were stained only weakly and/or homogeneously, and there was little evidence of cell polarity. Some of them were vacuolated. Ultrastructurally, they were round and devoid of ruffled borders and clear zones. The findings suggest that YM175 decreases the number and activity of osteoclasts. In addition, a few showed the morphology of cell death, which seemed to be one of the reasons leading to the decrease of osteoclasts. There was no substantial change in the morphological relationships or ultrastructure of osteoclast precursor cells, stromal cells, extracellular matrices, and tumor cells between the experimental and the control groups. In the experimental group, the distribution of extracellular matrices (heparan sulfate proteoglycan and fibronectin) was less conspicuous, but the localization of osteotropic cytokines (interleukin-6 and prostaglandin E2) was essentially similar to that of the control group. The cause leading to the decrease of osteoclast precursor cells remains to be clarified. In conclusion, YM175 inhibits bone resorption induced by tumor, by decreasing the activity of mature osteoclasts and possibly affecting the production of osteoclast precursor cells.

Acid Phosphatase↗
PubMed1994

Osteoblasts mediate thyroid hormone stimulation of osteoclastic bone resorption.

Thyroid hormones increase bone turnover in vivo and stimulate bone resorption in vitro. Clinical states associated with excess circulating thyroid hormone levels are known to produce osteoporosis. To determine the effect of T3 on bone resorption, we used an isolated rat osteoclast bone resorption assay in the absence or presence of added osteoblasts. This makes it possible to distinguish between direct and indirect effects of thyroid hormones on osteoclasts. In short settlement osteoclast cultures, which contain relatively few osteoblasts, 24-h treatment with T3 (10(-10)-10(-8) M) produced no stimulation of bone resorption. However, after 48-h incubation in the presence of T3, an increase in resorption was observed (2.3-fold at 10(-9) M). In cocultures of osteoclasts and osteoblasts (UMR 106-01 osteoblast-like cells or long settlement cultures), T3 stimulated resorption at 24 h. Furthermore, stimulation of resorption occurred when osteoblasts (UMR 106-01 or rat calvarial cells) were pretreated with T3 and the subsequent osteoblast-osteoclast cocultures conducted for 24 h in the absence of T3. Thus, direct exposure of osteoclasts to T3 was not required for the stimulatory effect. Treatment for 48 h with T3 (10(-9) M) or PTH (10(-8) M) had no effect on bone resorption in osteoblast-free cultures derived from human osteoclastoma tumours. T4 was 100-fold less potent than T3 as a stimulator of osteoclast activity, and rT3 had no effect. T3-induced stimulation was inhibited by salmon calcitonin (10(-10) M). These findings indicate that thyroid hormone can act on osteoblasts to indirectly stimulate osteoclastic bone resorption.

Animals↗
PubMed1990

Morphological relationships between osteoclasts and bone resorption surfaces on mouse parietal bones.

Parietal bones from mice 1-20 weeks of age were histochemically stained for detection of acid-phosphatase activity and then observed by the light microscope to evaluate the distribution and shape of osteoclasts on the inner surface of their bones. After microscopic examination, the same bones were macerated by NaOCl to both remove organic materials and expose the mineralized surface. The inner surface was then examined by scanning electron microscopy and the observations were compared with the light micrographs of the areas where osteoclasts were located. The bone resorption areas were identified as well-demarcated rough areas, and corresponded to the areas where osteoclasts were distributed. In young mice, osteoclasts observed in the bone resorption areas, which were composed of accumulations of irregular concavities, were mainly polygonal or round in shape. In adult mice, elongated osteoclasts with longer or shorter cytoplasmic processes were predominant; the bone concavities were also elongated and gathered in a flame-like pattern. The findings suggest that osteoclasts change shape according to their resorptive activities and that the activities differ between growing bones and those where growth has ceased, probably in relation to the modeling and remodeling of the bone.

Acid Phosphatase↗
PubMed1983

Effect of calcitonin in pregnant rats on bone resorption in fetuses.

Fetal bone resorption was measured by an organ culture technique using fetuses from intact or thyroparathyroidectomized pregnant rats. These experiments were performed to investigate the effects of 1,25-dihydroxycholecalciferol (1,25-DHCC) and salmon calcitonin (SCT) in pregnant rats, on both fetal growth and fetal bone resorption. Pregnant rats were given 0.1-0.5 microgram 1,25-DHCC per day from day 17 of gestation: in intact rats bone resorption was increased and fetal growth decreased; 1,25-DHCC probably modified fetal bone resorption in the absence of fetal parathyroid secretion. Infusion of SCT in minipumps (30 mu./h) did not modify plasma calcium levels in either the mother or fetuses, neither was bone resorption altered. In 1,25-DHCC-treated rats, SCT infusion resulted in an increase in fetal weight and a decrease in fetal bone resorption. On the other hand, SCT infusion was found to facilitate phosphate accumulation in fetuses. At the end of the SCT infusion the SCT concentration was 450 ng/l in maternal plasma and 553 +/- 60 ng/l in fetal plasma. Salmon calcitonin was shown to cross the placental barrier in the rats; it may interact with the effects of 1,25-DHCC in the fetus.

Animals↗
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↗
PubMed1981

Tooth eruption depends on bone resorption: experimental evidence from osteopetrotic (ia) rats.

Resorption of alveolar bone around erupting teeth is known to be independent of tooth eruption. However, the failure of tooth eruption and reduction in bone resorption in the osteopetrotic rat mutation, incisors absent (ia), suggest that tooth eruption depends upon bone resorption. This hypothesis was tested by determining the effects of neonatal restoration of bone resorption in ia rats on eruption of first molars. Newborn ia rats were treated with irradiation and spleen cells and tooth eruption and bone resorption were examined 30 days later. In 24 treated ia rats at least two molars erupted in every rat and all four molars erupted in 14. In 24 untreated ia littermates, no molars erupted in 21, one molar erupted in two and two molars erupted in one rat. All molars erupted in 38 untreated normal littermates. Alveolar bone overlying unerupted first molars in untreated ia rats was not present in treated mutant littermates. Neonatally treated ia rats had osteoclasts with ruffled borders and no skeletal sclerosis by 30 days. Within 48 hours after treatment two types of osteoclasts could be found in treated rats. One type resembled those found in untreated ia littermates and the other those found in normal rats. These data suggest that failure of tooth eruption in ia rats is directly related to the reduction in bone resorption and that alveolar bone resorption is required for tooth eruption.

Animals↗
PubMed1988

Human macrophage colony-stimulating factor inhibits bone resorption by osteoclasts disaggregated from rat bone.

Colony stimulating factors (CSFs) regulate the survival, proliferation and differentiation of haemopoietic progenitor cells, as well as the functional activity of mature cells. Because the osteoclast is derived from haemopoietic tissue, and because osteoblastic cells produce CSFs, we tested the effects of several CSFs on bone resorption by osteoclasts disaggregated from neonatal rat long bone. We found that recombinant macrophage (M)-CSF was a potent inhibitor of bone resorption, causing significant inhibition at concentrations similar to those required to support the growth of macrophage colonies in agar. Unlike other inhibitors of osteoclastic resorption, M-CSF did not alter cytoplasmic motility in time-lapse recordings, suggesting that M-CSF may inhibit osteoclasts through a different transduction mechanism. None of the remaining cytokines tested (granulocyte-macrophage CSF, interleukin 3, interleukin 6, or interferon gamma) influenced bone resorption. M-CSF production may be a mechanism by which osteoblastic cells, which produce M-CSF, may regulate osteoclastic function. Alternatively, inhibition of osteoclastic resorption by a CSF that is responsible for amplification of the macrophage compartment may reflect a close lineage relationship between mononuclear phagocytes, in which M-CSF induces a diversion of lineage resources away from osteoclastic function.

Animals↗