ISSN:0884-0431    

DOI:10.1002/jbmr.5650080502

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

年代:1993

数据来源: WILEY

摘要:

AbstractIntegrins are a family of heterodimeric transmembrane glycoproteins that are known to mediate cell‐cell and cell‐matrix interactions. Members of the VLA (very late activation) family, which consists of β1integrin in association with the VLA α chains (α1–6), mediate adhesion of a wide range of cells to matrix proteins, such as fibronectin, collagen, and laminin, and may therefore be important for cell‐matrix interactions in bone. Integrin expression in human bone was studied immunohistochemically using cryostat sections of fracture callus, tumor‐associated reactive bone, and neonatal costochondral junctions, with a panel of well‐characterized antibodies against β1–4integrins, α1–6and αv integrins, and the αvβ3dimer (the classic vitronectin receptor). All cell types present in bone expressed β1and α5integrins; a subpopulation of osteoblastic cells expressed α4. The αv was uniformly expressed by osteoblasts but was heterogeneously expressed by osteocytes. Osteoclasts also expressed α2, αv, and αvβ3. These results demonstrate differential expression of a restricted range of integrins in bone. This supports the possibility that integrins may mediate the differing interactions of cells of the osteoblast and osteoclast l

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080503

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe studied the effect of menatetrenone, a vitamin K2homolog, on bone resorption stimulated by interleukin‐1α (IL‐1α), prostaglandin E2(PGE2), parathyroid hormone (PTH), and 1,25‐dihydroxyvitamin D3[1,25‐(OH)2D3]. Bone‐resorbing activity was assessed by measurement of calcium and hydroxyproline in the media and calvariae. IL‐1α (0.1–100 U/ml), 1,25‐(OH)2D3(1010‐10−7M), PGE2(10−9‐10−6M), and PTH (3 × 10−8‐3 × 10−7M) dose dependently increased the levels of calcium and hydroxyproline in the medium. Indomethacin (10−6M) completely inhibited bone resorption induced by IL‐1α and partially inhibited bone resorption induced by 1,25‐(OH)2D3. However, indomethacin did not affect the action of PGE2or PTH. Menatetrenone (3 × 10−6‐3 × 10−5M) inhibited the bone resorption induced by IL‐1α (2 U/ml), PGE2(10−7M), PTH (3 × 10−7M), and 1,25‐(OH)2D3(3 × 10−10M) in a dose‐dependent manner. Menatetrenone also inhibited the PGE2production stimulated by IL‐1α. These results indicate that menatetrenone may inhibit bone resorption through at least two different mechani

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080504

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

年代:1993

数据来源: WILEY

摘要:

AbstractRecent work has established that various bone‐resorbing hormones are able to activate phosphoinositide metabolism as well as eicosanoid production in osteoblast‐like cells, although the relationship between these pathways is unclear. We used pertussis toxin and indomethacin to inhibit the stimulation of [3H]arachidonic acid release and [3H]phosphoinositide turnover caused by treating primary cultures of mouse osteoblasts with fetal calf serum. We found (1) that pertussis toxin and indomethacin each inhibited both pathways and (2) that although pertussis toxin inhibited [3H]arachidonic acid release to a greater extent than indomethacin, [3H]inositol phosphate accumulation was inhibited rather more effectively by indomethacin. These data suggest that whereas ligands in fetal calf serum activate [3H]arachidonic acid release largely directly via the action of a pertussis‐sensitive G protein, activation of phosphoinositidase C is indirect, being substantially dependent upon eicosanoid production. These experiments suggest that serial activation of phospholipase A2and phosphoinositidase C may occur in osteoblasts and that only the former enzyme is regulated by a pertussis toxin‐sensitive G

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080505

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

年代:1993

数据来源: WILEY

摘要:

AbstractSpecific immunoassay systems for intact human osteocalcin (I‐OC) and its 26‐residue propeptide have been newly developed to assess their usefulness as biochemical markers of bone metabolism. Using human cultured osteoblastic periosteal cells, we monitored 24 h secretion of these molecules from the osteoblastic cells and also examined the deposition of Ca, P, and I‐OC on the extracellular matrix. At day 5, both I‐OC and its propeptide were secreted by osteoblastic cells in a concentration‐dependent manner by treatment with 1,25‐(OH)2D3. This propeptide was not detected in the serum of adult subjects but was detected in the serum of normal children, which confirmed this in vitro result of propeptide secretion. The secretion of I‐OC into medium transiently decreased at day 11, when the rapid accumulation of I‐OC, Ca, and P, namely mineralization, was observed on the extracellular matrix of osteoblastic cells, although secretion of the propeptide constantly increased throughout the culture period. Therefore, the ratio of the amount of propeptide to I‐OC in the supernatant markedly increased when mineralization started. These data demonstrate the superior specificity of propeptide as a marker of osteoblastic function in vitro compared with I‐OC and that monitoring the changes in propeptide to I‐OC ratios in the culture supernatant may be useful for predicting the timing of mineralization on the extracellular matrix

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080506

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe evaluated the association of weight and bone mass in elderly male and female subjects of the Framingham osteoporosis study, a subset of the Framingham study cohort. By examining the differences in the correlations of weight with bone mass among men and women in weight‐bearing and non‐weight‐bearing sites and weight change since early adulthood, we attempted to understand different ways in which weight or body mass index affects bone mass. During biennial examination 20 of the Framingham cohort (1988–1989), 693 women and 439 men (mean age 76 years) had proximal femur bone mineral density assessed by dual‐photon absorptiometry (DPA) and radius bone mass assessed by single‐photon absorptiometry. The majority of these subjects also had spine measurements by DPA. Subjects had been weighed repeatedly over 40 years. After adjusting for other factors affecting bone density, we found that both recent weight and body mass index explained a substantial proportion of the variance in bone mineral density for all sites in women (8.9–19.8% of total variance, allp<0.01) and for only weight‐bearing sites (femur and spine) in men (2.8–6.9% of total variance, allp<0.01). For bone mineral density at the proximal radius, weight and body mass index accounted for<1% of variance in men (pNS). Weight change since biennial examination 1 (1948–1951) was the strongest explanatory factor for bone mineral density among women at all sites, but weight change did not affect radius bone mineral density in men. The effect of weight and of weight change on bone mineral density was in general much less in men than in women. Our results suggest that the strong effect of weight on bone mineral density is due to load on weight‐bearing bones in both sexes. The sex difference is unexplained but may be due to adipose tissue production of estrogen in

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080507

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe literature suggests that Asians have lower bone mineral density and mass than whites. It has been proposed that these differences may be due to differences in height, weight, and factors other than ethnicity, but no study has made the appropriate direct comparisons. We compared total‐body bone mineral density and mass between Asian and white women while controlling for factors known to be associated with bone mineral density and mass. Measurements were made in 129 Asian (primarily of Chinese ancestry) and 274 white women. A subgroup was formed of women who did not have a history of alcoholism, premenopausal amenorrhea, kidney disease, estrogen use, birth control pill use, thyroid disease, steroid use, hysterectomy, or smoking. In both the main group and the subgroups, bone mineral mass was significantly lower in Asian than in white women, but after analysis of covariance with body weight, height, and age (or years since menopause) as covariates, the differences between ethnic groups disappeared, except in the large group of premenopausal women, in whom average bone mineral density in Asians actually exceeded (p<0.04) that in whites. The data set was also searched for Asian‐white pairs who matched on 17 characteristics related to bone mineral density and mass. In the resulting 16 matched pairs, bone mineral density and mass were not different between ethnic groups. Although Asian women have lower bone mineral mass than white women, when weight, height, and other factors are controlled, bone mineral density and mass do not differ between Asian and white wo

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080508

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

年代:1993

数据来源: WILEY

摘要:

AbstractRecently, the effects of interleukin‐1 (IL‐1) on bone resorption in organ culture have been shown to be inhibited by an interleukin‐1 receptor antagonist (IL‐1RA), a novel monocyte cytokine in the IL‐1 family. IL‐1RA, which binds to IL‐1 receptors and inhibits many of the effects of IL‐1α and β, has been purified, cloned, and expressed. We used IL‐1RA to investigate its effects on calcium homeostasis in vivo. After confirming that IL‐1RA completely inhibited the effects of IL‐1 on bone resorption in organ cultures, we tested the effects of IL‐1RA on hypercalcemia mediated by IL‐1 in normal mice and found that prolonged hypercalcemia provoked by IL‐1 was completely inhibited by IL‐1RA. The initial transient decrease in blood ionized calcium observed following an injection of IL‐1 was also abrogated. IL‐1RA had no effect alone on blood ionized calcium or on hypercalcemia mediated by parathyroid hormone (PTH) or PTH‐related protein (PTHrP). These data suggest that antagonists to the IL‐1 receptor may provide a useful therapeutic approach to osteoclastic bone resorption a

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080509

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

年代:1993

数据来源: WILEY

摘要:

AbstractThree stages of osteogenic differentiation can be identified in in vivo diffusion chamber cultures (DCC) of unselected marrow cells, namely, proliferation, differentiation, and maturation (mineralization). These stages were characterized correlatively by in situ differential cell counts, alkaline phosphatase activity, and mineral accumulation. In the present study, the ultrastructure of marrow cell DCC was examined after incubation for 3–21 days. Features characteristic of osteoblastic and chondroblastic differentiation were first noted in 12 day DCC. Sites of osteoblastic differentiation showed cell‐cell contacts associated with an increased cell density. The osteoblastic cells had long processes and were embedded in matrix with prominent fiber bundles reminiscent of collagen type I. The chondroblastic cells appeared solitary in areas of lesser cell density. By contrast to the long osteoblastic cell processes, they had short plasmalemmal projections and the matrix surrounding them contained single, thin, short fibers reminiscent of collagen type II, as well as proteoglycan granules. Both cell types showed prominent cytoskeletal elements, rough endoplasmic reticulum, and Golgi. One finding, previously unnoted in differentiating osteogenic cells, was mitochondria with condensed cristae that represent an increased rate of energy metabolism. These mitochondria were particularly abundant in the differentiation stage and declined as the cultures matured. These findings, together with previous reports in the epiphyseal growth plate, suggest that mineralization is associated with an optimal level of energy metabolism rather than extreme hypo‐ or hyperoxia. The set of ultrastructural parameters defined here in the marrow cell DCC may serve as useful markers for cells undergoing osteogenic differenti

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080510

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

年代:1993

数据来源: WILEY

摘要:

AbstractOsteopenia is a typical finding in patients suffering from anorexia nervosa. Unfortunately, available longitudinal studies are limited by a relatively short follow‐up period. Therefore cross‐sectional long‐term follow‐up studies may help to determine both the outcome of this bone lesion and variables that influence its subsequent development. Of an initial 66 consecutive patients with anorexia nervosa, 51 (77.3%) could be further evaluated. After an average of 11.7 years following first admission, cross‐sectional measurements of lumbar and proximal radial bone mineral density (BMD) were performed. The ability to predict BMD using variables obtained from anamnestic and clinical data was then determined by multiple‐regression analysis. The BMD of both radial and lumbar bone in anorexic patients with poor disease outcome (as defined by the Morgan‐Russell general outcome categories) deviated by −2.18 and −1.73 SD (Z score), respectively. In patients with a good disease outcome lumbar BMD was significantly less reduced compared with radial BMD (–0.26 versus −0.68 SD). Variables reflecting estrogen deficiency and nutritional status in the course of the disease, that is, relative estrogen exposure (for lumbar BMD) and years of anorexia nervosa (for radial BMD), allowed the best prediction of BMD. A marked reduction in cortical and trabecular BMD in anorexic patients with poor disease outcome suggests a higher risk of fractures in these patients. Furthermore, the finding of a persistently reduced cortical and a slightly reduced trabecular BMD, even in patients with good disease outcome, suggests that a recovery of trabecular BMD might be possible, at least in part. Recovery of cortical bone, if possible at all, seems t

ISSN:0884-0431    

DOI:10.1002/jbmr.5650080511

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

年代:1993

数据来源: WILEY