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Results for “Bone Resorption”

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PubMed1999

Effect of cytokines on in vitro bone resorption by cells isolated from giant cell tumor of bone.

OBJECTIVE: To investigate the effect of cytokines on in vitro bone resorption by cells isolated from giant cell tumor of bone. METHODS: Mononuclear stromal cells and multinucleated giant cells (MGC) were isolated from 11 cases of giant cell tumor of bone (GCT) and their bone resorption capability in an in vitro cell-bone resorption model were tested. Expressions of some cytokines were detected by immunohistochemistry, Western blotting analysis and Enzyme-linked immunoabsorbent assay (ELISA) in the GCT. RESULTS: The results showed that MGCs of GCT had capability to resorb bone matrix directly. Fibroblast-like stromal cells (FC) could not only resorb bone matrix directly, but also secret unknown factors to facilitate bone resorption of MGC. Exogenous TNF-alpha could significantly increase the bone resorption by both kinds of stromal cells, while exogenous IL-1 did not. Expression rate of M-CSF and level of TNF-alpha in GCT were higher than in osteosarcoma and normal serum. CONCLUSIONS: The characteristic bone resorption behavior of GCT might be caused by its three major cell components. The M-CSF and TNF-alpha could promote their bone resorption capability.

Animals↗

PubMed1986

Osteoblast-like cells in the presence of parathyroid hormone release soluble factor that stimulates osteoclastic bone resorption.

PTH stimulates osteoclastic bone resorption in vivo and in organ culture. We have previously found that if osteoclasts are disaggregated from bone and incubated on bone slices, PTH does not increase bone resorption, but does so if osteoblastic cells are added to the cultures. This suggests that PTH acts primarily on osteoblasts, which are induced by the presence of the hormone to stimulate osteoclastic bone resorption. In the present paper we describe investigations into the mechanism by which osteoblastic cells stimulate osteoclasts. We found that increased resorption could not be accounted for by changes in the bone substrate. Osteoblast-like cells (UMR106) incubated with PTH did, however, release a factor into the culture supernatant that stimulated osteoclastic bone resorption. This factor was stable for at least 7 days when stored at 4 C and survived freeze-thawing, but was inactivated by heating to 65 C for 30 min. Activity was lost entirely after dialysis using a Spectrapor membrane with a mol wt cut-off (MWCO) of 2000. The small size of the molecule was confirmed after ultrafiltration across Amicon filters YM2 and YC05. There was no loss of activity across YM2 (MWCO, 1000), but, in contrast, there was no stimulation in the conditioned medium after ultrafiltration across YC05 (MWCO, 500).

Animals↗

PubMed1986

Stimulation of prostaglandin E2 and bone resorption by recombinant human interleukin 1 alpha in fetal mouse bones.

Recombinant human interleukin 1 alpha (rhIL-1 alpha) stimulates prostaglandin E2 and bone resorption in cultured forearm bones of fetal mouse in a dose-dependent manner: the minimal rhIL-1 alpha to elicit a significant bone resorption was 1.6 ng/ml (89 pM). The half maximal concentrations to elicit bone resorption and thymocyte proliferation were 3.3 ng/ml (183 pM) and 0.31 ng/ml (17 pM), respectively. The bone resorbing activity induced by IL-1 was partially inhibited by indomethacin and hydrocortisone, and completely inhibited by anti-IL 1-antibody. There was a good correlation between PGE2 production and bone resorption induced by IL-1 alpha. These results suggest that rhIL-1 alpha stimulates bone resorption at approximately 10 times the concentrations necessary for thymocyte proliferation and that PGE2 produced in the bone is at least in part involved in osteoclastic bone resorption.

Animals↗

PubMed2001

Inhibition of cholesteatomatous bone resorption with pamidronate disodium.

Bone destruction is known to be an important cause of complications in chronic cholesteatomatous otitis media. A strategy that blocks localized bone resorption may prevent the progression of the disease. The bisphosphonate drug pamidronate is known to inhibit bone resorption and has been used in the treatment of Paget's disease and osteoporosis. The aim of this study was to investigate the effect of pamidronate on the inhibition of bone resorption in cholesteatoma using a neonatal rat calvarial culture system. Radioactive calcium was subcutaneously injected into pregnant rats. Neonatal calvariae were harvested after i.p. injection of pamidronate disodium to neonatal rats and culture supernatants of cholesteatoma keratinocytes were then added to the calvarial culture media. Radioactive calcium release was measured using a beta-ray scintillation counter. The percentage of calcium release was significantly higher in cholesteatoma culture supernatant than in Dulbecco's modification of Eagle's medium. The percentage calcium release in cholesteatoma culture supernatant was significantly lower with the high dose of pamidronate than with the low dose. These results suggest that pamidronate can inhibit the bone resorption caused by cholesteatoma. This study suggests a possible application for pamidronate in the prevention of cholesteatomatous bone destruction.

Animals↗

PubMed2001

1alpha-Hydroxyvitamin D3 suppresses trabecular bone resorption by inhibiting osteoclastogenic potential in bone marrow cells after ovariectomy in mice.

To test the hypothesis that 1alpha-hydroxyvitamin D3 (1alpha(OH)D3) suppresses bone resorption after ovariectomy (ovx) by inhibiting osteoclastogenic potential in bone marrow cells, the bilateral tibiae of ddY mice, 8 weeks of age, subjected to ovx were obtained. 1alpha(OH)D3, at doses of 0, 0.2 (low dose), or 0.4 microg/kg body weight (high dose), was administered orally by canula three times a week for 2 or 6 weeks. Histomorphometric analysis of the proximal tibiae revealed that 1alpha(OH)D3 administration had no significant effect on trabecular bone volume of ovx limbs, which was reduced after ovx. The bone formation rate, increased by ovx, was significantly decreased by the administration of high-dose 1alpha(OH)D3. The ovx-induced increases in osteoclast number and surface at 2 weeks postsurgery were suppressed by the administration of high-dose 1alpha(OH)D3. With regard to bone marrow cells, the number of nonadherent cells per tibia obtained from ovx limbs increased, and this increase was suppressed by the administration of low- and high-dose 1alpha(OH)D3. The formation of mineralized nodules in marrow cultures obtained from ovx limbs was increased after surgery and unaltered by 1alpha(OH)D3 administration. The number of osteoclast-like multinucleated cells obtained from ovx limbs was reduced by low- and high-dose 1alpha(OH)D3 administration alike. The number of colony forming units-fibroblast and the number of colony forming units for granulocytes and macrophages was unaltered by ovx or the administration of 1alpha(OH)D3. The present study clearly demonstrates that high-dose 1alpha(OH)D3 suppresses osteoclast numbers and surface after ovx. The inhibitory effects of low- and high-dose 1alpha(OH)D3 on bone marrow cells after ovx were marked in the differentiation from osteoclast precursors to mature osteoclasts. Administration of 1alpha(OH)D3 suppressed ovx-promoted trabecular bone resorption by inhibiting osteoclastogenic potential in bone marrow cells.

Alkaline Phosphatase↗

PubMed1987

Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption.

Cytokines with bone-resorbing activity include IL 1 beta (pI 7), IL 1 alpha (pI 5), tumor necrosis factor (TNF), and lymphotoxin (LT). Possible interaction between IL 1 beta, the major mediator with osteoclast-activating factor (OAF) activity, and other cytokines was studied. By itself, IL 1 beta was 13-fold more potent than IL 1 alpha and 1000-fold more potent than either TNF or LT in stimulating bone resorption. Suboptimal concentrations of IL 1 beta or IL 1 alpha in combination with suboptimal concentrations of TNF or LT resulted in synergistic bone-resorptive responses (1.5 to 10 times the expected responses if their effects were additive). Synergy between either form of IL 1 and TNF or LT resulted in a twofold increase in activity of IL 1, and a 100-fold increase in activity of TNF or LT. However, even with optimal synergy, IL 1 beta remained 20-fold more potent in inducing bone resorption than TNF or LT. Because IL 1 beta is considerably more potent than TNF and LT in stimulating bone resorption either alone or under synergistic conditions, it is unlikely that TNF and LT are responsible for more than a minor proportion of the total bone-resorbing activity formerly referred to as OAF.

Animals↗

PubMed1998

Inhibition of bone resorption by 17beta-estradiol in human bone marrow cultures.

Estrogen deficiency puts individuals at risk of developing osteoporosis because it causes increased bone resorption. However, the mechanism by which this occurs is not known. We have shown, using a recently described two-phase human bone marrow culture system, that estradiol (17beta-E2) added to phase I results in inhibition of bone resorption by reducing the number of osteoclasts (identified as vitronectin receptor and/or calcitonin receptor-positive cells) formed in the cultures. The addition of 17beta-E2 in phase II was without effect, indicating that it does not interfere with the bone resorptive process. 17Beta-E2 down-regulated mRNA expression and protein synthesis of the membrane form of macrophage colony-stimulating factor (M-CSF). 17Beta-E2 did not the alter the expression of the 4.0 kb M-CSF transcript. However, it increased protein synthesis of the proteoglycan form of M-CSF, but not the 85 kDa soluble form in the same cultures. Finally, addition of M-CSF to the cultures reversed the 17beta-E2-induced inhibitory effect. These observations suggest that regulation of the synthesis of membrane-bound M-CSF plays a role in 17beta-E2-induced inhibition of bone resorption.

Actins↗

PubMed2005

Expression of heparanase by primary breast tumors promotes bone resorption in the absence of detectable bone metastases.

Heparanase is an enzyme that cleaves heparan sulfate and through this activity promotes tumor growth, angiogenesis, invasion, and metastasis in several tumor types. In human breast cancer patients, heparanase expression is associated with sentinel lymph node metastases. However, the precise role of heparanase in the malignant progression of breast cancer is unknown. To examine this, a variant of MDA-MB-231 cells was transfected with the cDNA for human heparanase (HPSE cells) or with vector alone as a control (NEO cells). Transfection produced a 6-fold increase in heparanase activity in HPSE cells relative to NEO cells. When injected into the mammary fat pads of severe combined immunodeficient mice, the tumors formed by HPSE cells initially grow significantly faster than the tumors formed by NEO cells. The rapid growth is due in part to increased angiogenesis, as microvessel densities are substantially elevated in primary HPSE tumors compared with NEO tumors. Although metastases to bones are not detected, surprisingly vigorous bone resorption is stimulated in animals bearing tumors formed by the HPSE cells. These animals have high serum levels of the C-telopeptide derived from type I collagen as well as significant elevation of the active form of tartrate-resistant acid phosphatase (TRAP)-5b. In contrast, in animals having a high tumor burden of Neo cells, the serum levels of C-telopeptide and TRAP-5b never increase above the levels found before tumor injection. Consistent with these findings, histologic analysis for TRAP-expressing cells reveals extensive osteoclastogenesis in animals harboring HPSE tumors. In vitro osteoclastogenesis assays show that the osteoclastogenic activity of HPSE cell conditioned medium is significantly enhanced beyond that of NEO conditioned medium. This confirms that a soluble factor or factors that stimulate osteoclastogenesis are specifically produced when heparanase expression is elevated. These factors exert a distal effect resulting in resorption of bone and the accompanying enrichment of the bone microenvironment with growth-promoting factors that may nurture the growth of metastatic tumor cells. This novel role for heparanase as a promoter of osteolysis before tumor metastasis suggests that therapies designed to block heparanase function may disrupt the early progression of bone-homing tumors.

Adenocarcinoma↗

PubMed2005

Optimized transfection of diced siRNA into mature primary human osteoclasts: inhibition of cathepsin K mediated bone resorption by siRNA.

Osteoclasts are large multinucleated cells responsible for bone resorption. Bone resorption is dependent on the liberation of calcium by acid and protease destruction of the bone matrix by proteinases. The key proteinase produced by the osteoclast is cathepsin K. Targeted knock-down of cathepsin K was performed using small inhibitory RNA (siRNA). siRNA is a method that introduces short double-stranded RNA molecules that instruct the RNA-induced silencing complex (RISC) to degrade mRNA species complementary to the siRNA. Transfection of siRNA by lipid cations allows for short-term inhibition of expression of the targeted gene. We show that transfection of primary human osteoclasts with siRNA to cathepsin K reduces expression by > or = 60% and significantly inhibits bone resorption with a reduction of both resorption pit numbers (P = 0.018) and resorbed area (P = 0.013). We also show that FuGENE 6 is an effective lipid transfection reagent with which to transfect primary human osteoclasts, that does not produce off-target effects.

Bone Resorption↗

PubMed2000

IL-10, but not IL-4, suppresses infection-stimulated bone resorption in vivo.

Periapical bone resorption occurs following infection of the dental pulp and is mediated mainly by IL-1alpha in the murine model. The production and activity of IL-1alpha is modulated by a network of regulatory cytokines, including those produced by Th1 (pro-inflammatory) and Th2 (anti-inflammatory) subset T cells. This study was designed to assess the functional role of the Th2-type cytokines IL-4 and IL-10 in infection-stimulated bone resorption in vivo. The dental pulps of the first molars were exposed and infected with a mixture of four common endodontic pathogens, and bone destruction was determined by micro-computed tomography at sacrifice on day 21. The results demonstrate that IL-10(-/-) mice had significantly greater infection-stimulated bone resorption in vivo compared with wild-type mice (p < 0.001), whereas IL-4(-/-) exhibited no increased resorption. IL-10(-/-) had markedly elevated IL-1alpha production within periapical inflammatory tissues (>10-fold) compared with wild type (p < 0.01), whereas IL-4(-/-) exhibited decreased IL-1alpha production (p < 0.05). IL-10 also suppressed IL-1alpha production by macrophages in a dose-dependent fashion in vitro, whereas IL-4 had weak and variable effects. We conclude that IL-10, but not IL-4, is an important endogenous suppressor of infection-stimulated bone resorption in vivo, likely acting via inhibition of IL-1alpha expression.

Animals↗

PubMed2003

Analysis of bone resorption after secondary alveolar cleft bone grafts before and after canine eruption in connection with orthodontic gap closure or prosthodontic treatment.

PURPOSE: We sought to analyze the success rate of secondary alveolar cleft bone grafts before and after canine eruption in connection with orthodontic gap closure or gap opening. PATIENTS AND METHODS: Sixty-eight secondary alveolar cleft bone grafts with iliac crest spongiosa were carried out in 57 patients (mean age, 9 years; age range, 8 to 11 years) with 11 bilateral and 46 unilateral clefts of the lip, alveolus, or palate. Gap closures were carried out after 53 bone grafts (78%), and gap openings with subsequent dental implants were carried out with 15 bone grafts (22%). The parameters acquired radiologically (orthopantomograms) at the time of the surgery and the follow-up examination (mean age, 3 years; age range, 7 months to 9 years) were 1) bone resorption in relation to the interdental height of the alveolar process in the vicinity of the cleft and 2) root growth of the teeth in the vicinity of the cleft. The statistically significant differences (P <.05) were monitored with a software program. Resorption grades I and II (>50% of the interalveolar bone height) were considered to be a success. RESULTS: Resorption was grade I in 69%, grade II in 19%, grade III in 10%, and grade IV in 1% of cases. Thus, the overall success rate was 88%. At the time of the osteoplasty, the root growth of the tooth in the immediate vicinity of the cleft was fully completed in 27 teeth (39%), three-quarters completed in 23 teeth (26.5%), and semicompleted in 18 teeth (33.8%). Twelve teeth (18%) in the vicinity of the cleft (lateral incisors/canine) remained unerupted and displaced after the surgery. It was necessary to expose unerupted teeth surgically to reposition them orthodontically. The resorption losses were significantly lower with gap closures than with gap openings (P <.001). However, bone grafts performed before canine eruption were largely carried out with the objective of orthodontic gap closure, in contrast to the bone grafts that were carried out after canine eruption (P <.02). CONCLUSION: Gap closures provide more favorable results than do gap openings in regard to resorption. Controlled dental eruptions or orthodontic gap closures reduce the graft resorption. The exact timing of surgery proved to be only a secondary consideration.

Alveolar Process↗

PubMed2001

Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin.

Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investigate the possible requirement for OPN in the transduction of mechanical signaling in bone metabolism in vivo, we examined the effect of unloading on the bones of OPN(-/-) mice using a tail suspension model. In contrast to the tail suspension-induced bone loss in wild-type mice, OPN(-/-) mice did not lose bone. Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN(-/-) mice. Analysis of the mechanisms of OPN deficiency-dependent reduction in bone on the cellular basis resulted in two unexpected findings. First, osteoclasts, which were increased by unloading in wild-type mice, were not increased by tail suspension in OPN(-/-) mice. Second, measures of osteoblastic bone formation, which were decreased in wild-type mice by unloading, were not altered in OPN(-/-) mice. These observations indicate that the presence of OPN is a prerequisite for the activation of osteoclastic bone resorption and for the reduction in osteoblastic bone formation in unloaded mice. Thus, OPN is a molecule required for the bone loss induced by mechanical stress that regulates the functions of osteoblasts and osteoclasts.

Amino Acids↗

PubMed2006

Benefits of an implant platform modification technique to reduce crestal bone resorption.

PURPOSE: The alveolar bone resorption that occurs around a 2-piece implant following abutment attachment is a well-documented observation. Several investigators propose that crestal bone loss is a response to the invasion of the biologic width by secondary bacterial colonization and micromovements at the implant-abutment interface. This study proposes the creation of a difference between the diameter of the implant platform and diameter of the abutment (implant platform modification), shifting the implant-abutment interface medially to minimize invasion of the biologic width. MATERIAL AND METHODS: We present a series of 30 control cases and 30 study cases using the platform-modification technique. Interproximal bone resorption on the medial and distal of each implant was assessed using digital radiography at 1, 4, and 6 months after abutment attachment. RESULTS: The mean value of bone resorption observed in the mesial measurement for the control group was 2.53 mm, whereas for those patients included in the study group, it was 0.76 mm. The mean value of bone resorption observed in the distal measurement for patients in the control group was 2.56 mm, whereas for those included in the study group, it was 0.77 mm. CONCLUSIONS: All patients in the study group had a significant reduction of bone loss in comparison to the control group (P < 0.0005).

Alveolar Bone Loss↗

PubMed1989

Calcitonin receptors as markers for osteoclastic differentiation: correlation between generation of bone-resorptive cells and cells that express calcitonin receptors in mouse bone marrow cultures.

The osteoclast is the cell that resorbs bone. It is known to derive from hemopoietic precursors, but analysis of lineage and regulation of differentiation has been hampered by lack of a specific marker that enables identification of cells of osteoclastic phenotype. Previously used markers, such as multinuclearity, that are specific for osteoclasts in bone become less specific in culture. Uniquely among bone and bone marrow cells, osteoclasts possess abundant calcitonin (CT) receptors. We therefore tested the correlation between the generation of bone-resorptive function and the formation of CT receptor-positive cells from hemopoietic tissue in vitro. Without 1,25-dihydroxy-vitamin D3 [1,25-(OH)2D3], a hormone that induces osteoclastic differentiation in vitro, bone marrow cultures showed very little bone resorption, and only small numbers of CT receptor-positive cells developed. When 1,25-(OH)2D3 was added to the cultures, CT receptor-positive cells developed within 1 day and reached a peak after 7 days. Bone resorption commenced within 2 days of hormone addition. There was a strong parallelism between the cumulative number of CT receptor-positive cells and the extent of bone resorption. The capacity of cultures to generate bone-resorptive activity and CT receptor-positive cells declined progressively when 1,25-(OH)2D3 was added to hemopoietic tissue after a 7- to 21-day hormone-free incubation period. The number of CT receptor-positive cells in these cultures correlated strongly (r = 0.96) with bone resorption. The behavior of these cultures suggests that 1,25-(OH)2D3 acts to induce terminal differentiation of osteoclast precursors present in the cultures, and that precursor cell numbers decreased with increasing time in vitro. All of the CT receptor-positive cells in control cultures and all of those seen shortly after 1,25-(OH)2D3 addition were mononuclear, despite considerable bone resorption; the majority of CT receptor-positive cells remained mononuclear throughout the incubation period. This suggests that mononuclear cells with characteristics of osteoclasts exist that are able to excavate bone. CT receptor-positive cells slightly preceded the development of bone-resorptive function, implying that CT receptors develop before the acquisition of bone-resorptive capacity by osteoclasts. Peritoneal macrophages, blood mononuclear cells, and cells of the J774 macrophage cell line failed to either resorb bone or express CT receptors, even after incubation with 1,25-(OH)2D3 for 14 days. These results show a strong and specific correlation between the generation of bone-resorptive cells and CT receptor-positive cells, and suggest that CT receptor express

Animals↗

PubMed1994

Comparison of the effects of 3,5,3'-triiodothyroacetic acid and triiodothyronine on bone resorption in cultured fetal rat long bones and neonatal mouse calvariae.

Thyroid hormones can stimulate bone resorption both directly and indirectly by increasing endogenous prostaglandin (PG) synthesis. Because 3,5,3'-triiodothyroacetic acid (Triac, Tiratricol) can bind to nuclear thyroid hormone receptors with high affinity, we compared the effects of Triac and 3,5,3'-triiodothyronine (T3) on bone resorption. 45Ca release was measured at 2, 5, and 8 days from 19-day-old-fetal rat long bones in the presence or absence of calcitonin, indomethacin, aphidicolin (APC), cortisol, or interleukin-1 receptor antagonist (IL-1ra). Both Triac and T3 stimulated 45Ca release in a dose-dependent manner. The maximal treated/control ratio (T/C) for Triac (10(-7) M) was 1.6 +/- 0.1 at 2 days and 2.5 +/- 0.1 at 5 days and, for T3 (10(-7) M), 1.5 +/- 0.1 at 2 days and 2.6 +/- 0.1 at 5 days. These responses were smaller and slower than that to PTH. Significant stimulation of resorption was observed at 10(-8), 10(-9), and 10(-10) M for Triac but only at 10(-8) and 10(-9) M for T3. Indomethacin (10(-6) M) and IL-1ra (1 microgram/ml) did not decrease the effects of Triac or T3. In contrast, calcitonin (10(-9) M), APC (30 microM), and cortisol could all block the response to these hormones. These results indicated that the resorptive responses were not mediated by endogenous PG or IL-1 but were osteoclast mediated and dependent on DNA synthesis, suggesting that these hormones acted by stimulating replication of osteoclast precursors or other supporting cells. Thyroid hormones were less effective in 7-day-old neonatal mouse calvariae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2001

Clinical disorders of bone resorption.

Clinical disorders in which bone resorption is increased are very common and include Paget's disease of bone, osteoporosis, and the bone changes secondary to cancer, such as occur in myeloma and metastases from breast cancer. Clinical disorders of reduced bone resorption are less common and often have a genetic basis, e.g. in osteopetrosis, and in pycnodysostosis due to cathepsin K deficiency. Bone is metabolically active throughout life. After skeletal growth is complete, remodelling of both cortical and trabecular bone continues and results in an annual turnover of about 10% of the adult skeleton. The commonest disorder of bone resorption is osteoporosis, which affects one in three women over 50 years. Its pathophysiological basis includes genetic predisposition and subtle alterations in systemic and local hormones, coupled with environmental influences. Treatment depends mainly on drugs that inhibit bone resorption, either directly or indirectly. This includes bisphosphonates, oestrogens, synthetic oestrogen-related compounds (SERMs--selective oestrogen receptor modulators) and calcitonin. The most widely used drugs for all disorders of increased bone resorption, including osteoporosis, are the bisphosphonates. Recent elucidation of their mode of action, together with the rapidly increasing knowledge of regulatory mechanisms in bone biology, offers many opportunities for the development of new therapeutic agents.

Animals↗

PubMed1995

Heparin fails to potentiate the effects of IL-1 beta-mediated bone resorption of fetal rat long bones in vitro.

Heparin has been identified as a potent modulator of bone resorption. Heparin induces osteoporosis during long-term administration and has been shown in vitro to enhance the effects of other bone resorbing factors, including parathyroid hormone. In this study, we examined the effects of heparin on the bone-resorbing activity of the inflammatory cytokine IL-1 beta. Resorption was determined by measuring release of previously incorporated 45Ca from fetal rat long bones cultured in medium supplemented with either 0.1% bovine serum albumin or 10% heat-inactivated fetal calf serum. Heparin, in the absence of serum, decreased basal resorption at 4 and 10 units/ml, and slightly increased resorption at 30 units/ml. Heparin had no effect on IL-1 beta-stimulated resorption. In the presence of serum, heparin induced a two-fold increase in resorption alone, however, when cocultured with IL-1 beta, heparin failed to further enhance IL-1 beta-stimulated resorption.

Animals↗

PubMed1996

Gold salts inhibit osteoclastic bone resorption in vitro.

Loss of bone mass is commonly associated with rheumatoid arthritis (RA) and is increasingly considered to be due to the increased activity of bone-resorbing osteoclasts. Gold salts such as auranofin (AF), aurothioglucose (ATG) and aurothiomalate (ATM) have beneficial therapeutic effects in RA, but their mechanisms(s) of action is not well understood. In the present study we have examined the effects of these 3 gold salts on osteoclastic bone resorption in vitro, using the bone slice assay where bovine cortical bone slices are resorbed by osteoclasts disaggregated from the long bones of neonatal rats. All 3 gold salts inhibited osteoclastic bone resorption with IC50 values of AF = 0.1 microgram/ml, ATG and ATM = 1 microgram/ml. All 3 compounds caused a decreased survival of osteoclasts on bone slices at high concentrations indicating a cytotoxic effect that was also observed in a cytotoxicity assay with osteoblast-like UMR-106 cells. Preincubation of bone slices with various concentrations of AF followed by extensive washing prior to use in the bone slice assay also resulted in an inhibition of bone resorption (IC50 = 4 micrograms/ml) and osteoclast survival on the bone slices preincubated with high concentrations of AF was decreased. Since these effects were obtained with therapeutic concentrations of gold salts, these results indicate that inhibition of osteoclastic bone resorption by gold salts may, at least in part, account for their beneficial effects in RA.

Animals↗