摘要:

AbstractPurified chick duodenal brush border membrane vesicles (BBMV) were used to assess the effect of vitamin D on intestinal Ca2+transport and membrane stability. BBMV preparations are right‐side‐out as judged by a nine‐fold increase in accessibility of lactoperoxidase to core material actin in the presence of Triton X‐100. Freshly prepared BBMV from vitamin D‐deficient chicks support both sodium‐dependent glucose transport and Ca2+uptake.In vivotreatment with 1,25(OH)2D3results in an 85% increase in theVmaxof Ca2+‐uptake from 2.2 to 3.9 nmol/min/mg protein. TheKmof Ca2+‐uptake (0.9 mM) is independent of the vitamin D status of the chick. The majority of BBMV derived from vitamin D‐replete chicks were destabilized and rendered incapable of supporting either sodium‐dependent glucose uptake or Ca2+uptake if they were held at 0–4°C for 2 to 24 h. In 40 separate experiments, 80% of membranes derived from vitamin D‐replete chicks showed characteristics of destabilization, whereas only 24% of all control membranes exhib

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010402

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe diterpene forskolin which increases 3′,5′‐cyclic adenosine monophosphate concentrations (cAMP) in intact cells by directly activating the enzyme adenyl cyclase, was examined for its ability to alter bone resorption in fetal rat long bone cultures. After 48 h, forskolin inhibited resorption at 1.0 and 10 μ However, after 120 h, it had a small stimulatory effect at 1.0 μMand no net effect on resorption at 10 μ Isobutylmethylxanthine (IBMX), which elevates cAMP levels in cells by inhibiting the enzyme 3′,5′‐cyclic adenosine monophosphate phosphodiesterase, produced a resorptive response which was slightly different from that of forskolin. After both 48 and 120 h, IBMX at 0.1 mMstimulated resorption while at 1.0 mM, it had only inhibitory effects. In bones which were stimulated to resorb with either parathyroid hormone or 1,25(OH)2vitamin D, forskolin inhibited resorption. The inhibitory effects of forskolin on hormonally stimulated resorption were transient in cultures treated with 1.0 μMbut were sustained with 10 μM. Inhibitory responses to forskolin did not appear to result from toxicity since they were completely reversed when forskolin was removed from the media.These results imply that agents which increases 3′,5′‐cyclic adenosine monophosphate concentrations in bone activate two resorptive pathways: one which is inhibitory and anothe

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010403

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe hormone‐sensitive adenylate cyclase system of a cloned bone cell line (UMR‐106) derived from a rat osteosarcoma was compared in preparations from cells of early passages (<50) and cells maintained in continuous culture for over two years (late passages). Late passage cells showed greater calcitonin (CT)‐stimulated adenylate cyclase activity than did early passages, whereas stimulation by PTH and the β‐adrenergic agonist isoproterenol decreased in late passages. Hormone concentrations giving half‐maximal stimulation were the same in early and late passages. Stimulation by agents (GTP and fluoride) which act at the stimulatory guanine nucleotide regulatory component (Ns) of adenylate cyclase was equivalent in early and late passages. Forskolin stimulation, which assessed catalytic component (and possibly Ns) activity, was reduced in late passages. These results are consistent with acquisition by cultured UMR‐106 cells of CT receptors linked to adenylate cyclase and loss of PTH and β‐adrenergic receptors. Alteration of catalytic component (and/or Ns) function may also occur after long‐term culture. Since late passage cells appear dedifferentiated by chromosomal analysis and since cAMP may regulate differentiation, altered hormone‐sensitive adenylate cyclase may be a marker for and a potential modulator of differentiation occurring in UMR‐106 ce

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010404

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

年代:1986

数据来源: WILEY

摘要:

AbstractOsteoclasts, the multinucleated resorbing cells of bone, are identified by their characteristic morphology, unique cell membrane specializations, and more recently by the presence of cell surface antigens recognized by monoclonal antibodies. They are derived from mononuclear precursor cells of hematogenous origin. The precise relationship between osteoclasts and other types of tissue giant cells is unknown. This study was designed to examine factors involved in the recruitment and differentiation of multinucleated cells and to investigate the relationship between so‐called foreign body giant cells and bone‐resorbing osteoclasts.Particles of various materials were implanted into subcutaneous pockets in rats. Histological, histochemical, and electron microscopic evaluations were made of specimens harvested 12 days after implantation. Large, foamy multinucleated cells were evident around particles of devitalized bone, polyethylene, and polymethylmethacrylate. Bone particles showed scalloped surfaces and were partially resorbed. Those cells adjacent to the bone particles stained positive for tartrate‐resistant acid phosphatase, in contrast to the multinucleated cells adjacent to the other materials. All the cell types had extensive rough endoplasmic reticulum, abundant mitochondria, cytoplasmic vacuoles and dense bodies, giant centrospheres, and areas of fusion of plasma membranes. Cells in lacunae on the surface of the bone particles showed a clear zone of attachment to the bone substrate and ruffled borders, a feature characteristic ofin ossoosteoclasts. Although the giant cells occasionally displayed an extensive clear zone of attachment to the polyethylene and polymethylmethacrylate particles, no ruffled borders were detected.The results of these studies show that the multinucleated cells elicited in response to different materials, although sharing many common features, do demonstrate certain features that are substrate specific. This model can be used to investigate the relationship between osteoclasts and other types of multinucleated giant cells and to help elucidate factors involved in osteoclast recruitment, differentiation, and regul

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010405

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

年代:1986

数据来源: WILEY

摘要:

AbstractSerum bone GLA‐protein (BGP), a sensitive and specific marker of bone formation, was measured in 54 normal children and in 50 children with growth disorders. In normal children, the pattern of variations of serum BGP with age was similar to the pattern of variations of the growth velocity. Mean serum BGP was very high during the first year of life (25.3 ± 8.5 ng/ml), decreased to 14.8 ± 2.2 ng/ml from 2 to 6 years, increased to 18.4 ± 4.1 ng/ml from 7 to 10 years and to 18.8 ± 6.5 ng/ml from 11 to 14 years. After puberty, mean sBGP decreased to 12.9 ± 5.4 ng/ml from 15 to 18 years and to 6.5 ± 1.4 ng/ml in young adults. In 32 patients with untreated growth hormone (GH) deficiency, mean sBGP was markedly lower than in age matched controls (6.8 ± 4.4 ng/ml vs. 17.5 ± 4.9 ng/ml,p<.001). In 19 patients with GH deficiency who were undergoing treatment with human GH, sBGP was higher than in untreated patients (20.5 ± 9.3 ng/ml vs. 6.8 ± 4.4 ng/ml,p<.001) and was not different from controls. Repeated measurements performed in 14 GH‐deficient patients under chronic GH therapy showed that serum BGP: (1) increased in most patients during treatment (p<.005); (2) was correlated with the duration of treatment (p<.001); (3) decreased to pretreatment values after discontinuing therapy. In conclusion, our data suggest that serum BGP is a sensitive marker of skeletal growth in normal children and in children with growth deficiency, and that measurement of serum BGP might be useful to assess the effects on bone metabolism of hormones and/or drugs that stimulate bone growth a

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010406

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

年代:1986

数据来源: WILEY

摘要:

AbstractSome data suggest that human calcitonin (CT) secretion is lower in women than in men, decreases with age and the menopause, and is absent in thyroidectomized persons. To further explore CT secretory physiology, we have studied basal and calcium‐stimulated plasma immunoreactive CT (iCT) and silica‐extractable monomeric CT concentrations in 148 healthy volunteers and 33 patients with a history of thyroid damage (total or subtotal thyroidectomy, radioiodine treatment for thyrotoxicosis). Both whole‐plasma iCT and extractable CT levels were lower basally and after calcium infusion in women than in men, basal levels being reduced about 50% and calcium‐stimulated values about 75% from those of male subjects. There were no significant changes in basal iCT or extractable CT concentrations with age, and CT secretory capacity (CT response to calcium infusion) likewise did not change with age. Infusion of monomeric CT to constant concentration in 27 persons permitted estimates of CT metabolic clearance rates (MCRs) and secretion rates (SRs). Calculated MCRs of about 9 ml/min · kg−1(persons aged 21–30 yr) and 6 ml/min · kg−1(persons aged 54–70 yr) were in good agreement with published data, and did not differ between the sexes. SRs were dependent upon the assay method used to estimate basal plasma CT concentrations, being highest when whole‐plasma iCT values were used. Based on estimates of plasma monomeric CT from the silica extraction procedure, the SR of CT was 59 ± 6 (SE) ng/d · kg−1in men, and 22 ± 3 ng/d · kg−1in women. Thyroid damage reduced, but did not abolish, apparent CT immunoreactivity, even in silica extracts of plasma. However, all subsets of thyroiddamaged patients had absent‐to‐markedly‐impaired CT secretion in response to calcium infusion. We conclude that CT secretion is substantially lower both basally and after stimulation in women than in men, and that this difference in CT immunoreactivity probably reflects differences in circulating CT bioactivity. The sex difference in plasma CT concentrations probably results from lower rates of CT secretion in women, not increased MCR. There is no age‐related decrease of plasma CT concentrations (or CT secretory reserve), calling into question the concept that a progressive deficiency of CT is partly resonsible for age‐related (“senile”) osteoporosis. Surgical or radiation damage to the thyroid gland commonly abolishes C‐cell response to calcium; such CT‐deficient patients form a population suitable for determining whether or not reduced

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010407

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

年代:1986

数据来源: WILEY

摘要:

AbstractWe have found that the cytochemical bioassay (CBA) method, originally developed to measure circulating levels of biologically active parathyroid hormone (bioPTH) in humans, also can measure endogenous concentrations of PTH in rats. Therefore, we have applied this assay method to examine the relationships between age and sex and the circulating levels of bioPTH, calcium, and phosphorus in Fischer rats. The concentration of bioPTH increased in both males and females from 5 to 15 months of age (p<.001) with no significant sex‐related difference. Mean bioPTH values ranged from 2.3 to 3.6 pg (human PTH equivalents)/ml; these values were much lower (1 to 2 orders‐of‐magnitude) than those reported by others who used radioimmunoassays for PTH that do not discriminate between biologically active and inert PTH fragments. The CBA values for bioPTH were also 1/4–1/5 those obtained in rat serum by newer, more sensitive methods, the N‐terminal specific PTH radioimmunoassay and the bioassay based on stimulation of chick renal adenylate cyclase.Regression analysis did not reveal any significant correlation between serum calcium and age. However, serum inorganic phosphorus decreased significantly (p<.001) from 5 to 15 months of age in both male and female rats and was much lower in females than in males (p<.001). The fall in serum phosphorus was negatively correlated with the rise in bioPTH (p<.001).This study, the first to our knowledge to use a CBA to detect physiological changes in the circulating levels of bioPTH in rats, demonstrates the usefulness of the assay in experiments in thi

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010408

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

年代:1986

数据来源: WILEY

摘要:

Abstract1α, 25‐dihydroxyvitamin D3[1α,25(OH)2D3] directly induces both fusion and cytotoxicity in murine alveolar macrophages. Unlike 1α,25(OH)2D3, retinoic acid per se did not induce fusion of alveolar macrophages, but it greatly enhanced the 1α,25(OH)2D3‐induced fusion every time the macrophages were treated simultaneously with the two vitamins. The giant cells induced by the two vitamins were much larger than those induced by 1α,25(OH)2D3alone. The macrophages treated with 1α,25(OH)2D3started to fuse 36 h after the addition of the vitamin, whereas the macrophages pretreated with retinoic acid for 24 h began to fuse immediately after 1α,25(OH)2D3was added. 1α,25(OH)2D3and retinoic acid activated alveolar macrophages similarly, measured by the enhancement of glucose consumption and the induction of cytotoxicity against tumor cells, though 1α,25(OH)2D3was 100 times more potent than retinoic acid on a molar basis. Simultaneous treatment with physiological concentrations of 1α,25(OH)2D3(0.12 nM) and retinoic acid (10 nM) induced cytotoxicity additively. Morphological examinations revealed that the treated cells were enlarged and flattened with numerous filopodia. These results clearly indicate that both 1α,25(OH)2D3and retinoic acid similarly activate alveolar macrophages, and the activated state is prerequisite to the fusion of macrophages induced b

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010409

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

年代:1986

数据来源: WILEY

摘要:

AbstractOsteoporosis of the spine and femoral neck is a major problem in aging populations, but detection prior to a fracture remains a challenge. Forearm bone mineral content has been advocated as a useful screening test in this situation. We have examined the correlation between distal forearm bone mineral content, by single photon absorptiometry, and lumbar vertebral and femoral neck bone mineral density, by dual photon absorptiometry. Eighty women aged 20 to 76 years were studied and significant correlations (p<.001) were found between the measurements on the forearm and at the two axial sites (r= 0.66 and 0.69, respectively). However, forearm bone mineral content was an unreliable predictor of axial bone mineral density. For prediction of lumbar spine osteopenia with a sensitivity of 88%, the false positive rate was 91%. Conversely, to achieve a specificity of 82%, the false negative rate was 65%. Similarly, for prediction of femoral neck osteopenia at a sensitivity of 92%, the false positive rate was 87%, and at a specificity of 90%, the false negative rate was 33%. These data demonstrate that forearm bone densitometry cannot be used as a screening procedure for osteopenia of the lumbar spine or femoral neck.

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010410

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

年代:1986

数据来源: WILEY

摘要:

AbstractDaily subcutaneous injection of a synthetic human parathyroid hormone fragment, combined with daily ingestion of 1,25(OH)2vitamin D, significantly increased trabecular bone density in the spine (p<.01), and improved intestinal calcium and phosphorus absorption and total body retention of dietary calcium and phosphorus in middle‐aged men with idiopathic osteoporosis. The increases in spinal bone mineral were marked and progressive during a year of treatment. These results indicate that increasing intestinal absorption of dietary calcium while simultaneously stimulating new bone formation with small doses of parathyroid hormone can restore spinal bone in osteoporotic me

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010411

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

年代:1986

数据来源: WILEY