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At least 19 recordsLinked to original sources

PubMed1996

Bone sialoprotein stimulates in vitro bone resorption.

Bone sialoprotein (BSP) is a protein highly specific for bone, which contains an arginine-glycine-aspartic acid (RGD) cell attachment sequence involved in osteoclast adhesion to bone matrix via the vitronectin receptor. We have investigated its role in in vitro bone resorption using the well described isolated osteoclast resorption pit assay. BSP significantly stimulates bone resorption in a dose-dependent manner, increasing the overall resorbed area on ivory slices and the number of lacunae at concentrations as low as 50 nM. Neither recombinant osteopontin nor intact vitronectin has any effect on bone resorption, suggesting a specific effect of BSP. The stimulation of bone resorption induced by BSP could be partially explained by an increase in osteoclast adhesion to bone via its RGD sequence, and our results suggest another mechanism of action of BSP that might involve another region of the molecule, such as its acidic sequences. Although BSP stimulates bone resorption in a coculture system of bone marrow cells and osteoblastic cells, it dose dependently inhibits the formation of osteoclast-like cells at equivalent concentrations in this culture model. In conclusion, we provide evidence that BSP plays an important role in the bone resorption process and may regulate bone resorption as well as osteoclast formation.

Animals↗

PubMed1987

The establishment of a new biological assay system for simultaneous measurement of bone resorption and bone mineralization in organ cultures of chick embryonic femur.

A biological assay system has been developed for the simultaneous measurement of bone resorption and bone mineralization. In this system we (1) used chick embryonic femur as the biological material because of the easy handling and easy specification of developmental stages compared with rat and mouse, (2) labeled bone with 45Ca in vitro, (3) calculated the biological half life (T1/2) of 45Ca incorporated into bone salts for quantitative estimation of the bone resorbing activity, and (4) investigated bone-mineralizing activity by determining the calcium content before and after cultivation. Eleven-day-old chick embryonic femur was labeled with 45Ca in a chemically defined medium in vitro and thereafter labeled bones were transferred to chase medium. T1/2 was calculated from the sequential release of the label into the medium from the cultured bone. No one heretofore had determined the T1/2 of Ca in bone salts. We first determined in this study that the T1/2 of Ca in the chick embryonic femur is about 50 h. The decrease in T1/2 by parathyroid hormone, prostaglandin E1 and E2 and lipopolysaccharide, well-known stimulators of bone resorption, showed that this system works well in terms of bone resorption. By using this system, we demonstrated that immunomodulators such as Bacillus Calmette Guerin and Corynebacterium paruvum stimulate bone resorption and therefore affect bone metabolism. On the contrary, sodium fluoride (NaF) and hydrocortisone increased T1/2, indicating that they inhibit bone resorption. These agents were also tested to determine if they would alter total calcium in the bone during cultivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

The effect of calcium supplementation on the circadian rhythm of bone resorption.

Bone resorption shows a circadian rhythm in human subjects, but the physiological mechanisms underlying this rhythm are unknown. We compared the circadian rhythm of bone collagen degradation in 18 premenopausal women before and after oral calcium supplementation (1000 mg calcium for 14 days). Subjects were randomized to receive calcium at either 0800 h or 2300 h. Continuous 48-h urine collections and 1 day of 4-h urine collections were obtained before and after the 14-day supplementation period. We measured urinary deoxypyridinoline (Dpd) and the cross-linked N-telopeptide of type I collagen (NTx) as biochemical markers of bone resorption. There was a significant effect of time of day on excretion of Dpd and NTx (analysis of variance, P < 0.001) with peak excretion between 0300-0700 h and a nadir between 1500-1900 h. The mean amplitude (peak to trough) was similar for Dpd and NTx (70.3% and 63.3%, respectively). Evening calcium supplementation resulted in marked suppression of the nocturnal increase in Dpd and NTx and reversed the usual nocturnal increase in the level of parathyroid hormone. In contrast, morning calcium supplementation had no significant effect on the circadian rhythm of Dpd or NTx. Evening calcium supplementation suppressed overall daily excretion of Dpd by 20.1% (P = 0.03) and NTx by 18.1% (P = 0.03). Morning calcium supplementation had no significant effect on overall daily excretion of either Dpd or NTx. We conclude that evening calcium supplementation suppresses the circadian rhythm of bone resorption. The daily rhythm of PTH secretion or calcium intake is likely to be an important determinant of this rhythm. Experimental protocols designed to investigate the effect of calcium supplementation on bone mineral density should take the timing of supplementation into account.

Adult↗

PubMed1977

Pathogenesis of osteopetrosis in the microphthalmic mouse: reduced bone resorption.

Bone resorption, stimulated by injection of parathyroid extract, was measured in vivo in microphthalmic mice as the rate of release of 3H from bone after incorporation of 3H-proline. Bone resorption in these mice, which inherit osteopetrosis, was less than 10% of the in normal litermates. Autoradiography confirmed the reduction in removal of radioactive bone matrix and in bone growth in microphthalmic mice. The ability of these mice to raise the serum calcium concentration in response to PTE was also reduced. These results, that bone resorption is reduced in microphthalmic mice, are discussed in relation to the pathogenesis and cure of the disease.

Animals↗

PubMed1995

H-31 human breast cancer cells stimulate type I collagenase production in osteoblast-like cells and induce bone resorption.

Bone is one of the most common sites of metastasis in breast cancer. For metastasis to occur in bone, tumor cells must induce osteolysis by osteoclasts. Degradation of the osteoid layer by type I collagenase is a necessary process before osteolysis can occur because the osteoid layer hinders osteoclasts from adhering to bone. In this study, we investigated the function of H-31 human breast cancer cells in inducing type I collagenase production and in enhancing bone resorption. H-31 cells did not themselves produce type I collagenase whereas MG-63 human osteoblast-like cells and MC3T3-E1 mouse osteoblast cells constantly produced type I collagenase. When these osteoblast-like cells were cocultured with H-31 cells, type I collagenase production was enhanced. The same enhancement occurred when the conditioned medium of H-31 cells was added to the osteoblast-like cells. The activity of this type I collagenase was inhibited by EDTA and minocyclin, an inhibitor of matrix metalloproteinases, hence it was identified as matrix metalloproteinase-1 (MMP-1). H-31 cells exhibited chemotactic migration towards collagen; therefore, collagen degraded by MMP-1 may play an important role in the localisation of breast cancer cells like H-31 to bone. In an organ culture system using newborn mouse calvaria, the conditioned medium of H-31 cells increased the concentration of calcium in the medium, and this effect was inhibited by minocyclin, indicating that bone resorption occurred in this system. Based on these observations, we speculate that type I collagenase produced by osteoblast cells in response to breast cancer cells (exemplified by H-31) may facilitate degradation of the osteoid layer and the homing of breast cancer cells to bone. This can lead to osteolysis by osteoclasts, a crucial event for bone metastasis.

Bone Resorption↗

PubMed1997

Characterization of the osteoclast ruffled border chloride channel and its role in bone resorption.

Bone resorption by osteoclasts requires massive transcellular acid transport, which is accomplished by the parallel action of a V-type proton pump and a chloride channel in the osteoclast ruffled border. We have studied the molecular basis for the appearance of acid transport as avian bone marrow mononuclear cells acquire a bone resorptive phenotype in vitro. We demonstrate a critical role for regulated expression of a ruffled border chloride channel as the cells become competent to resorb bone. Molecular characterization of the chloride channel shows that it is related to the renal microsomal chloride channel, p64. In planar bilayers, the ruffled border channel is a stilbene sulfonate-inhibitable, outwardly rectifying chloride channel. A mechanism by which outward rectification of the single channel chloride current could allow efficient regulation of acidification by the channel is discussed.

Animals↗

PubMed2003

Low estrogen and high parathyroid hormone-related peptide levels contribute to accelerated bone resorption and bone loss in lactating mice.

Providing enough calcium for milk production stresses calcium homeostasis in lactating mammals. A universal response to these demands for calcium appears to be the mobilization of maternal skeletal reserves, and bone loss during lactation has been well documented. However, the regulation of calcium and skeletal metabolism during lactation remains enigmatic. Our study was designed to examine mineral and bone metabolism in lactating mice. We found that mice lose bone rapidly at all sites during lactation. Bone mineral density as determined by dual-energy x-ray absorptiometry was 20 to 30% lower at the spine, femur, and total body in lactating compared with either age-matched virgin or pregnant mice. The decrease in bone mineral density was accompanied by dramatic reductions in bone volume and changes in trabecular architecture. Bone loss was also accompanied by increases in bone turnover as determined by biochemical markers and histomorphometry. PTHrP levels were elevated during lactation and correlated positively with markers of bone resorption and negatively with bone mass at all sites. Estrogen levels were low during lactation and correlated negatively with bone resorption markers. Finally, estrogen and pamidronate treatment lowered rates of bone resorption to baseline virgin levels and mitigated, but did not prevent, bone loss. These data suggest that the combination of estrogen deficiency and elevations in circulating PTHrP during lactation act to stimulate bone resorption and promote bone loss.

Animals↗

PubMed2000

Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts.

Bone morphogenetic proteins (BMPs) play an important role in various kinds of pattern formation and organogenesis during vertebrate development. In the skeleton, BMPs induce the differentiation of cells of chondrocytic and osteoblastic cell lineage and enhance their function. However, the action of BMPs on osteoclastic bone resorption, a process essential for pathophysiological bone development and regeneration, is still controversial. In this study, we examine the direct effect of BMPs on osteoclastic bone-resorbing activity in a culture of highly purified rabbit mature osteoclasts. BMP-2 caused a dose- and time-dependent increase in bone resorption pits excavated by the isolated osteoclasts. BMP-4 also stimulated osteoclastic bone resorption. The increase in osteoclastic bone resorption induced by BMP-2 was abolished by the simultaneous addition of follistatin, a BMP/activin binding protein that negates their biological activity. Just as it increased bone resorption, BMP-2 also elevated the messenger RNA expressions of cathepsin K and carbonic anhydrase II, which are key enzymes for the degradation of organic and inorganic bone matrices, respectively. Type IA and II BMP receptors (BMPRs), and their downstream signal transduction molecules, Smad1 and Smad5, were expressed in isolated osteoclasts as well as in osteoblastic cells, whereas type IB BMPR was undetectable. BMPs directly stimulate mature osteoclast function probably mediated by BMPR-IA and BMPR-II and their downstream molecules expressed in osteoclasts. The results presented here expand our understanding of the multifunctional roles of BMPs in bone development.

Animals↗

PubMed1983

Effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP) upon the kinetics of bone resorption and bone formation at the whole bone level in prelabelled chicks.

Chicks chronically prelabelled with 45Ca, 3H-tetracycline, and 3H-proline were used to measure the weekly effect of EHDP (5 mg P/kg for 28 days) on bone turnover at the whole bone level in vivo. Direct measurements were made of cortical bone resorption (loss of 3H-tetracycline and 3H-collagen from whole femur, blood-bone ratio of 45Ca), skeletal collagen formation and bone mineralization (collagen and calcium mass per whole femur, respectively). Chicks were sacrificed after 5, 14, 21 and 28 days of EHDP administration. By five days of treatment, EHDP caused a greater inhibition of bone mineralization (86%) than bone resorption (30-39%) without affecting skeletal collagen mass. The blood-bone ratio of 45Ca decreased 34%, which was similar in degree to the inhibition of 3H-tetracycline loss (30%) and 3H-collagen loss (39%). Almost complete inhibition of bone resorption and bone mineralization occurred by 14 days of treatment without effects on skeletal collagen mass. No additional effect was seen at 21 and 28 days of EHDP treatment. In chicks, EHDP inhibits almost completely bone mineralization (bone formation) and cortical bone resorption without affecting skeletal collagen mass.

Animals↗

PubMed1988

Effects of chronic prednisolone treatment on bone resorption and bone composition in intact and ovariectomized rats and in ovariectomized rats receiving beta-estradiol.

To examine the interactions between estrogen deficiency and glucocorticoid excess on bone metabolism the osteopenic effects of a standard dose of prednisolone (2 mg/kg BW.day) were studied in sham-ovariectomized (Sham-OVX), ovariectomized (OVX), and OVX rats given replacement beta-estradiol (OVX + E2). For 12 weeks six groups of female albino rats aged 4 months which had their skeletons labeled with 45Ca were fed matched amounts of low-calcium (0.1% Ca) hydroxyproline-free diet. The six treatment groups were: group 1, Sham-OVX; group 2, Sham-OVX + prednisolone; group 3, OVX; group 4, OVX + prednisolone; group 5, OVX + E2; group 6, OVX + E2 + prednisolone. Bone resorption was estimated by studying the urinary excretion of hydroxyproline and 45Ca. Parathyroid function was assessed indirectly from urinary cAMP excretion. Treatments did not influence parathyroid activity or serum levels of calcium or 1,25-dihydroxyvitamin D. However, ovariectomy increased bone resorption and induced osteopenia whereas prednisolone decreased bone resorption and formation and caused osteopenia. Ovariectomy increased the rate of bone resorption in prednisolone-treated rats; prednisolone lowered the rates of bone resorption and formation in OVX rats. The osteopenic effects of prednisolone and ovariectomy were additive and independent. E2 protected bone from the osteopenic effects of ovariectomy but did not affect bone loss induced by prednisolone. These results suggest prophylactic estrogen should help to avoid bone loss from estrogen deficiency in patients requiring chronic high dose glucocorticoid treatment.

Animals↗

PubMed1975

Growth and remodeling of bone. An investigation in chicken with special reference to the mechanism of bone resorption.

Bone resorption was studied in chicken by means of histologic and microradiographic examination after intravital injections of three boneseeking fluorochromes. The fluorochromes were injected at intervals from 36 hours to 5 days, and the chicken were killed at 36 hours to 10 days after injection of the third fluorochrome. Signs of osteolysis, such as enlarged osteocyte lacunae surrounded by a metachromatic zone in toluidine blue stained sections, and confluence of osteocyte lacunae in microradiographs, were compared with the fluorochrome labelling pattern. There was no correlation between the histologic findings of osteolysis and the fluorochrome resorption pattern which indicated that existence of so-called bone flow. In the "haversian systems" at midshaft level, the color pattern remained unchanged till resorption took place from the endosteal side. Osteoclasia seemed to be the dominant mode of resorption. The conclusion was drawn that bone flow does not exist in the tibiae of chicken.

Animals↗

PubMed2000

Retardation in bone resorption after bone marrow ablation in klotho mutant mice.

The klotho gene mutant mice exhibit both osteopetrotic phenotype, including elongation of trabeculae in the epiphyses of long bones and vertebral bodies, and osteopenic phenotype, such as thin cortical bones in the diaphyses of these bones. These diverse features raise the question of whether the klotho gene defect results in alteration in bone resorption in vivo. Therefore, we examined the effect of the klotho gene defect on bone resorption by using bone marrow ablation model. At 1 week after bone marrow ablation, trabecular bones were formed in the ablated marrow cavity to levels higher than those in unablated bones in both klotho mutant and wild-type mice. At 2 weeks postsurgery, newly formed trabecular bones were resorbed in wild-type mice to resume normal bone marrow and trabecular bone volume fraction as reported previously. In contrast, the newly formed trabecular bones in the ablated marrow in klotho mutant mice remained at levels similar to those at 1 week. The defect in the bone resorption phase in klotho mutant mice is associated with site-specific reduction of the number and size of osteoclasts in klotho mutant mice. Moreover, the expression levels of osteoprotegerin messenger RNA in the ablated femora of klotho mutant mice were higher than those in wild-type mice. These results indicate that lack of klotho gene expression suppressed bone resorption that should normally take place 2 weeks after bone marrow ablation.

Animals↗

PubMed2003

Genistein prevents bone resorption diseases by inhibiting bone resorption and stimulating bone formation.

UNLABELLED: Genistein, a soybean-derived isoflavone, has been shown to suppress osteoclastic bone resorption. To clarify the mechanisms underlying this action, we investigated the effects of genistein on the differentiation, cytoskeleton and function in mice osteoclasts in vitro and bone metabolism in ovariectomized rats. STUDY DESIGN: Primary OCs were isolated from 3 week-old mice and induced by 1,25(OH)(2)D(3). Then OCs were exposed to genistein at various concentration of 0 M, 10(-9) M, 10(-8) M, 10(-7) M, 10(-6) M, and 10(-5) M. The number of TRAP+ cells were counted as well as the surface area of bone resorption on bone slice. F-actin change was observed by Confocal. In vivo, forty 12 week-old female SD rats were randomly assigned to four groups: (1) sham operated (Sham); (2) (OVX); (3) ovariectomized and treated with estradiol (OVX-E); (4) ovariectomized and received genistein (OVX-G). After 12 weeks, BMD, body weight, serum level of alkaline phosphatase (ALP), acid phosphatase (ACP), osteocalcin (OC), IL-1beta, TNFalpha, IL-6 and calcitonin (CT) were evaluated. Femur were sectioned. In addition, the serum estradiol, the weight of uteri and histological behavior were also examined to indicate the side effect of genistein to the uteri. RESULTS: In vitro, the number of TRAP+ cells decreased depending on the concentration of genistein as well as the area of bone resorption. F-actin became disorder under Confocal. In vivo, after treated with genistein, BMD and the serum level of ALP, ACP, osteocalcin increased significantly, while the serum level of IL-1beta and TNFalpha decreased. Especially, the increase of ALP and osteocalcin of OVX-G was higher than that of OVX-E. Histologically, the pachy-trabecula were observed as well as the more mineral deposition lines. Additionally, the uterus weight index and the serum estradiol in OVX-G rats were lower significantly than those of OVX-E. The epithelia of uteri gland in OVX-G appeared cubic while those of OVX-E became squamous. CONCLUSIONS: Genistein can prevent bone resorption diseases by the promotion of bone formation and the prevention of bone resorption with slight side effect.

Absorptiometry, Photon↗

PubMed2003

Properties of bisphosphonates in the 13762 rat mammary carcinoma model of tumor-induced bone resorption.

Bone metastasis from primary tumors is a clinically important complication of neoplastic progression. The role of parathyroid hormone-related protein (PTHrP) and transforming growth factor (TGF)-beta1 in this process has been clearly established. The current study describes an in vivo model of 13762 rat mammary carcinoma tumor cell-induced osteolysis in which PTHrP and TGF-beta1 expression is observed. Exposure of in vitro-cultured 13762 cells to doxorubicin, cis-platinum, carboplatin, methotrexate, 5-fluorouracil, paclitaxel, alendronate, risedronate, or pamidronate for 72 h resulted in varying effects on cell proliferation (IC(50) values of 0.005, 0.4, 1.9, >40, 17.9, 0.003, >40, >40, and 33.6 micro M, respectively). Tumor cells were implanted into the intramedullary space of the proximal tibia of rats, and the time course of tumor progression was evaluated using radiographic and microcomputed tomography scanning techniques. Trabecular bone mineral density, cortical bone mineral density, and whole bone mineral density were measured (in mg/cm(3)). In untreated animals, radiographic evidence of osteolysis was evident 7 days after implantation. Trabecular bone mineral density and whole bone mineral density were significantly decreased by 21 days after implantation (48% and 26%, respectively). Bisphosphonates showed broad protective activity against tumor-driven osteolysis, Immunohistochemical evaluation of s.c. and intratibially implanted cells demonstrated the expression of PTHrP and TGF-beta1. The results of this study demonstrate the ability of 13762 rat mammary carcinoma cells to elicit a measurable osteolysis and that bisphosphonates inhibit the tumor-induced bone resorption in this model.

Animals↗

PubMed1998

[Recent advances in biology of bone resorption].

Bone resorption is a unique process which requires function of highly specialized cells, i.e., osteoclasts, Osteoclasts are terminally differentiated multinuclear cells that originate from multipotent hematopoietic stem cells and are closely related to the monocyte/macrophage lineage. Recent advances in molecular biological techniques and development of useful experimental systems both in vitro and in vivo have made it possible to identify several factors essential to osteoclast differentiation or function under physiological and/or pathological conditions. Such factors include transcription factors such as c-Fos and PU.1, cytokines such as IL-6 and TNF-alpha, and other various molecules such as tyrosine kinases and adhesion molecules. This review will focus on recent progress in our understanding of osteoclast biology.

Animals↗

PubMed1992

Stimulative effects of cadmium on bone resorption in neonatal parietal bone resorption.

Effects of cadmium on bone resorption were investigated using neonatal mouse parietal bone culture system. Cadmium at 0.5 microM and above stimulated hydroxyproline release as well as 45Ca release. As cadmium-stimulated bone resorption was inhibited by calcitonin, bone resorption induced by cadmium is osteoclast-mediated bone resorption. CI-1, collagenase inhibitor, depressed cadmium-stimulated bone resorption in a dose-dependent manner. Osteoblasts are also involved in cadmium-induced bone resorption. Indomethacin-inhibited cadmium-stimulated bone resorption and cadmium-treated bones released prostaglandin E2 to a greater extent than untreated bones. Cadmium-stimulated bone resorption was shown to be dependent on the production of prostaglandin E2. 3-Isobutyl-1-methylxanthine potentiated cadmium-stimulated bone resorption and verapamil depressed it. It is possible that an increase in levels of cAMP and calcium ion in bone cells is involved in cadmium-induced bone resorption. From these results, cadmium was found to stimulate osteoclast-mediated bone resorption which is dependent on prostaglandin E2. Second messengers in cadmium-induced bone resorption may be cAMP and calcium ion.

Animals↗

PubMed1997

[Interrelations of the calcium concentration in breast milk with maternal intake of cow's milk and milk products, bone resorption and bone mineral density during lactation].

The interrelations of the calcium (Ca) concentration in breast milk with maternal intake of cow's milk and milk products, 24-hour urinary hydroxyproline and Ca concentrations adjusted by creatinine (H.P/Cre, Ca/Cre) and bone mineral density measured by ultrasonic bone densitometry were examined to study the mechanism regulating the calcium concentration in breast milk. Subjects were 105 lactating women, aged 21 to 42 years, at 21.590 days postpartum. 1) The geometric means (logarithmically transformed calculated M +/- SD) of H.P/Cre were 40.7 (31-61) and 36.3 (28-47) mg/g in women lactating less than 150 days and 150 days or more, respectively. These values indicated increased bone resorption. 2) Intake of cow's milk and milk products significantly negatively correlated with urinary H.P/Cre. For women consuming less than 100ml per day of cow's milk, a significant positive correlation was found between the urinary H.P/Cre and Ca concentration in breast milk. These results suggest that the extent of bone resorption depends on maternal Ca intake and the Ca transfer from maternal bone to breast milk in women with a low Ca intake. 3) For women with a cow's milk intake of less than 100ml per day, a significant positive correlation was found between the Ca concentration in breast milk and bone mineral density, indicating that women with bone mineral loss are not able to compensate for the low Ca level in breast milk. 4) Urinary Ca/Cre significantly negatively affected the Ca concentration in breast milk. This result indicates that some amount of Ca in breast milk is due to renal conservation.

Adult↗

PubMed1997

Frequency of food intake and natural dietary components are potent modulators of bone resorption and bone mass in rats.

Prevention of low bone mass is important to reduce the incidence of osteoporotic fractures. In this report evidence is provided that feeding habits per se, that is, increased frequency of food intake as well as a diet containing soy and other raw components, decrease bone resorption and increase bone mass in growing rats. Interim results after 6 weeks indicate that food fractionation and natural dietary components are both capable of inhibiting trabecular bone loss in aged rats. These interim results indicate that the effect of both dietary interventions are additive and together are capable of nearly completely blunting the age-dependent loss of trabecular bone mineral density. These dietary manipulations are, however, only partially effective in inhibiting the strongly increased loss of trabecular bone mineral density induced by estrogen deprivation. The fact that the natural dietary components are not more effective in ovariectomized rats as compared to intact females confirms our contention that these components may not operate by mimicking the effect of estradiol. Whether bone mass in humans is also under the control of dietary habits is not known. If so, an increased frequency of meals of appropriate composition may be used to prevent osteoporosis.

Animals↗