ISSN:0884-0431    

DOI:10.1002/jbmr.5650030602

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractRecent studies have reported cellular effects of 1,25‐dihydroxyvitamin D3within 15 minutes, a time period too rapid to be mediated by nuclear activation. The vitamin increases hepatocyte cytosolic calcium levels in the absence of extracellular calcium within 5 minutes. Since metabolites of phosphatidylinositol have been implicated as second messengers in the regulation of cytosolic calcium, we examined the effect of 1,25‐dihy‐droxyvitamin D3on hepatocyte phosphatidylinositol turnover and compared these effects to those produced by vasopressin. In isolated hepatocytes labeled with [3H]inositol, 1,25‐dihydroxyvitamin D3(4 nM) increased [3H]glycerophosphoryIinositol by 16% (p<0.01) within 2.5 minutes, by 18% (p<0.01) after 5 minutes, and by 11% (p<0.05) after 10 minutes. At a concentration of 20 nM, 1,25‐dihydroxyvitamin D3increased [3H]glycerophosphorylinositol by 27% (p<0.01) after 5 minutes. Vitamin D did not affect [3H]inositol polyphosphates. Conversely, vasopressin had no effect on [3H]glycerophosphorylinositol but significantly increased [3H]inositol phosphate, [3H]inositol bisphosphate, and [3H]inositol trisphosphate. 1,25‐Dihy‐droxyvitamin D3(4 nM) decreased [3H]phosphatidylinositol by 10% (p<0.05) after 5 minutes and by 16% (p<0.01) after 10 minutes. At a concentration of 20 nM, 1,25‐dihydroxyvitamin D decreased [3H]phosphatidylinositol by 18% (p<0.01) after 5 minutes. The vitamin did not affect [3H]phosphatidylinositol bis‐phosphate or [3H]phosphatidylinositol trisphosphate. 24,25‐Dihydroxyvitamin D had no effect on inositol phospholipids. The effects of 1,25‐dihydroxyvitamin D3on inositol phospholipids were blocked by quinacrine. Bromophenacylbromide inhibited the effects of 1,25‐dihydroxyvitamin D3on inositol phospholipids and also blocked the vitamin‐induced increments in cytosolic calcium. In isolated hepatocytes labeled with [3H]arachidonic acid, 1,25‐dihydroxyvitamin D3(20 nM) decreased3H‐labeled phosphatidylcholine and phosphatidylethanolamine, as well as phosphatidylinositol. The data indicate that 1,25‐dihydroxyvitamin D3may enhance deacylation of hepatocyte phospholipids, perhaps by activation of phospholipase A activity. The ability of vitamin D to increase cytosolic calcium requires activation of phospholipase A. Although both 1,25‐dihydroxyvitamin D and vasopressin rapidly affect phospholipid metabolism,

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030603

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractBone density measurements are currently being performed throughout the world in the diagnosis and management of osteoporosis as well as in research into this major health problem. However, it is not clear to what extent bone mineral density (BMD) values determined by dual‐photon absorptiometry at one center can be applied to another. This is particularly relevant for the quantitative comparison of results from studies carried out in different laboratories. Furthermore, many centers now acquiring densitometers may not have the resources to determine their own normal range, relying instead on a “normal” range provided by the manufacturer. The question of the comparability of BMD data obtained in different centers was examined by comparing the normal range for the lumbar spine and proximal femur in 203 normal white Australian women and 892 normal white U.S. women, obtained using the same model densitometer.The two populations were compared according to decade. From superimposition of the Australian individual values on the North American normal ranges, only minor differences between the two populations were seen at any of the sites measured at any decade. None of these minor differences were statistically significant.This study shows a close similarity between BMD values in both the proximal femur and lumbar spine in normal white women in Australia and North America, provided the same model densitometer is used. Thus data obtained from different centers in populations with similar ethnic composition may be compared directly. These findings provide for the first time a sound basis for the quantitative comparison of the at times conflicting studies carried out in widely differing settings around the

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030604

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractThe effect of pertussis toxin, which inactivates the guanine nucleotide binding regulatory proteinsGiandGoon cAMP production in response to parathyroid hormone PGE2or forskolin, was examined in confluent opossum kidney (OK) cells. This effect was compared with that caused by dexamethasone. The response to PTH was increased in cells preincubated with either agent. The effect of pertussis toxin was selective for PTH, since cAMP production in response to neither PGE2nor forskolin was increased. In contrast, the response to forskolin was enhanced in dexamethasone‐treated cells. These results indicate that both stimulatory and inhibitory guanine nucleotides binding regulatory proteins modulate PTH‐induced cAMP producion in OK cells. Moreover, pertussis toxin and dexamethasone appear to affect different levels of the PTH‐receptor‐adenylate cyclase

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030605

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractWe have previously found that the adenylate cyclase stimulators forskolin and choleratoxin increase cyclic AMP and transiently inhibit bone resorption in cultured mouse calvaria, suggesting that the compounds, directly or indirectly, may inhibit osteoclast activity. In the present study, forskolin and choleratoxin were investigated for their direct effects on surface area and motility of isolated rabbit osteoclasts, and the effects were compared to those of calcitonin (CT). Osteoclasts were cultured on coverslips for different times in the absence or presence of the compounds. The effect on osteoclast mean area was quantified on fixed and stained osteoclasts, and in addition effects were recorded with time‐lapse cinemicrography. The effects of CT (100 mU/ml) on mean area and motility were seen within minutes and were maximal after 10–60 minutes. Forskolin (10–30 μmol/liter) produced a rapid (15–60 minutes) inhibition of motility and decrease in area (contraction) of osteoclasts. Choleratoxin (1 μg/ml) treatment also resulted in cell contraction and inhibition of motility; however, the response was not seen before 45–60 minutes. The difference in the kinetics of the osteoclast response between forskolin, CT, and choleratoxin is similar to differences in time course for the effect on cyclic AMP in calvarial bones, which we reported earlier. Although cells were incubated continuously with forskolin, choleratoxin, or CT, the effects were transient. Thus, after 7–8 h incubation with CT, 3–4 h treatment with forskolin, or 4–6 h with choleratoxin, the osteoclasts started to recover from contraction and immotility. The effect of forskolin and choleratoxin on the mean surface area of osteoclasts was dose dependent.The present study shows that forskolin and choleratoxin have a direct inhibitory action on osteoclast activity and thus provide further evidence that cyclic AMP is a mediator of the action of CT o

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030606

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractTumor necrosis factor α (TNF‐α) and interleukin‐1 (IL‐1) have been shown to stimulate bone resorption in vitro. We have now investigated whether these cytokines also cause a similar action when administered in vivo. This was made possible by the adaptation of a newly developed technique that enables the continual assessment of bone resorption in vivo in mice by measuring urinary excretion of3H from [3H]tetracycline‐prelabeled animals.Experiments using maneuvers known to influence bone resorption, such as a change in dietary calcium or administration of parathyroid hormone or dichloromethylenebisphosphonate, indicate that the technique is reliable and sensitive in mice.Daily intravenous administration of either recombinant human or recombinant murine TNF‐α, as well as subcutaneous administration of recombinant human IL‐1α, were found to stimulate bone resorption in a dose‐dependent manner. The effect was maximal within 2 days. Thus, exogenous TNF‐α and IL‐1α can stimulate bone resorption in vivo, suggesting that these cytokines may also exert a

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030607

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractCyclic adenosine monophosphate (cAMP) is thought to be a second messenger for the actions of both parathyroid hormone (PTH) and calcitonin (CT). We examined the release of cAMP from rat bone in vivo after administration of synthetic rat PTH‐(1–34) (rPTH), synthetic human PTH‐(1–34) (hPTH), or synthetic human CT (hCT). Blood from the venous effluent of the femoral bone of rats (bone blood) was drawn at 5 and 10 minutes after the administration of hormones. The cAMP content of the bone blood was then compared to the cAMP content of arterial blood. In both kidney‐clamped and non‐kidney‐clamped rats, hCT led to a significantly greater concentration of cAMP in the bone blood than in the arterial blood. We interpret this to be due to bone production and release of cAMP. Neither hPTH nor rPTH produced a significantly greater amount of cAMP in the bone blood than in arterial blood. These data do not preclude the possibility that there was a production of cAMP within the bone tissue itself after PTH but suggest that there was no release of cAMP from the bone into t

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030608

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractWe have reported that the differentiation‐inducing factor (DIF) is present in conditioned medium of mouse osteoblast‐like cell (MC3T3‐E1) cultures (Ref. 12). In the present study, the DIF from conditioned medium of MC3T3‐E1 cells was partially purified and its biologic activity was examined. The DIF was purified by monitoring the induction of phagocytic activity of mouse myeloblastic leukemia cells (M1). The DIF induced differentiation of not only M1 cells but also mouse myelomonocytic cells (WEHI‐3). Furthermore, the DIF increased the in vitro bone‐resorbing activity and the osteoclast number in mouse calvaria. The increases were inhibited by the addition of either salmon calcitonin or indomethacin. When mouse bone marrow cells were cultured with the DIF for 8 days, formation of osteoclast‐like multinucleated cells was stimulated dose dependently. The DIF from MC3T3‐E1 cells appeared to be different from interleukin‐1 (IL‐1), tumor necrosis factor (TNF), and transforming growth factor β (TGF‐β). These results suggest that the DIF partially purified from osteoblast‐like cell cultures stimulates osteoclastic bone resorption by promoting differentiation and fusion of osteoclast progenitors to form m

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030609

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractThe concept of resorption preceding formation in a coupled response is well established as the normal sequence of remodeling in adult bone. So prevalent is this concept, however, that the idea of the direct activation of osteogenic modeling in normal adult bone is often ignored. This experiment documents the direct transformation of the normal, quiescent, adult periosteum to active bone formation. The osteogenic stimulus was provided by a single short period of dynamic loading. Periosteal activation and the production of new bone within 5 days of loading was unaccompanied by resorption or the presence of osteoclasts. We therefore conclude that an adult resting periosteum can become directly converted to formation as a physiologic response to an appropriate osteogenic stimulus without the need for resorption. To distinguish this process from remodeling we suggest it be called renewed modeling. It is notable that a single short exposure to an “osteogenic” loading regime can influence the full cascade of cellular events between quiescence and active bone format

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030610

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY

摘要:

AbstractParathyroid hormone, prostaglandin E2, 1α,25‐dihydroxyvitamin D3, interleukin‐1, tumor necrosis factor α, and epidermal growth factor, all known stimulators of bone resorption, markedly enhanced collagenase secretion by rat fetus osteoblastlike cells in primary culture as judged by enzyme‐linked immunosorbent assay. Untreated cells contained no immunostainable or extractable collagenase. Collagenase was detected in the treated cells and media only after 1–3 h of treatment, and there was no increment in collagenase activity when cells were treated in the presence of actinomycin D or cycloheximide. Cells secreted collagenase in a latent form and also elaborated collagenase inhibitor; chromatographic separation of collagenase from collagenase inhibitor and subsequent activation of the collagenase with trypsin yielded the active species in stimulated but not in unstimulated cells. The ability of individual prostanoids, among seven tested, to promote collagenase production correlated positively with their reported capacity to promote bone resorption. Interferon‐γ (IFN‐γ), a known resorption inhibitor, blocked the increment in collagenase production caused by all agents tested. These results indicate a close linkage between stimulation of bone resorption and collagenase production by osteoblastlike cells. Various resorption stimulators, including some not previously tested for effects on collagenase, augment the de novo synthesis and secretion of collagenase and act by an IFN‐γ‐i

ISSN:0884-0431    

DOI:10.1002/jbmr.5650030611

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1988

数据来源: WILEY