ISSN:0884-0431    

DOI:10.1002/jbmr.5650051102

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

年代:1990

数据来源: WILEY

摘要:

AbstractTransforming growth factor β and fibroblast growth factor are mitogens for chick growth plate chondrocytes. TGF‐β stimulated a 3.5‐fold increase, and FGF a 13.5‐fold increase in the rate of thymidine incorporation after a 24 h exposure. TGF‐β and FGF were synergistic in chondrocytes, causing a 73‐fold stimulation in thymidine incorporation compared with control. This synergistic response was not dependent upon the simultaneous presence of both mitogens. Sequential exposure of chondrocytes to TGF‐β and FGF in either order reproduced in large part the synergistic interaction observed when both growth factors were present simultaneously. The time required for induction of the subsequent synergistic response was brief and, in the case of TGF‐β, corresponded to the time required for [125I]TGF‐β receptor binding. EGF and PDGF were not mitogenic for chondrocytes, and neither of these factors enhanced the response of the cells to either TGF‐β or FGF. Finally, TGF‐β and FGF did not, either alone or in combination, elevate intracellular cAMP levels. These results emphasize the importance of examining growth factor effects in the context of other growth regulators. Furthermore, this specific and dramatic synergistic stimulation of thymidine incorporation may provide a useful tool in elucidating the mitogenic mechanism of th

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051103

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

年代:1990

数据来源: WILEY

摘要:

AbstractA 59‐year‐old male presented with systemic mastocytosis with extensive skeletal involvement resulting in vertebral compression fractures and bone pain. Histomorphometric analysis of bone revealed increased mast cells, elevated static parameters of bone resorption, and low bone formation. Serum calcium, phosphorus, and alkaline phosphatase were normal; however, serum 1,25‐dihydroxyvitamin D3and osteocalcin levels were low. Histamine levels in plasma and urine were elevated. Following therapy with ketotifen, the patient had resolution of bone pain along with decreased flushing and pruritus. Elevated plasma and urine histamine levels normalized, as did 1,25‐dihydroxy vitamin D3and osteocalcin levels. Indices of low bone formation improved on therapy. Eroded surfaces improved but remained elevated. This case is the first demonstration that bone symptoms and histomorphometric change in systemic mastocytosis are reversed with inhibition of mast cell degranulation. The role of mast cells and their products in bone metabolism is poorly understood, but the therapy of bone disease in systemic mastocytosis should include inhibition of the release of mast cell products along with the use of histamine ant

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051104

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

年代:1990

数据来源: WILEY

摘要:

AbstractWe report serum 25‐hydroxyvitamin D (25‐OHD), 24,25‐dihydroxyvitamin D [24,25‐(OH)2D], and 1,25‐dihydroxyvitamin D [1,25‐(OH)2D] levels in untreated Paget's disease and the effect of treatment with either calcitonin (CT) or etidronate (EHDP) on these levels.In untreated Paget's patients serum 25‐OHD (73 ± 29 nmol/liter,n= 36, mean ± SD) and 24,25‐(OH)2D (0.3–12.9 nmol/liter, median 2.2,n= 36) levels were significantly lower than in age‐matched controls (94 ± 30 nmol/liter,n= 32,p<0.005, and 1.3–16.4 nmol/liter, median 5.3;n= 32,p<0.001, respectively). Also, the 24,25‐(OH)2D levels correlated with the 25‐OHD levels in the untreated Paget's patients (r= 0.56,p<0.01) and in the controls (r= 0.39,p<0.05). The percentage molar ratio of 24,25‐(OH)2D to 25‐OHD in Paget's patients had a median value of 3.7% (range 0.4–14.3%), which was not significantly different from controls, who had a median value of 5.6% (range 2.2–18%). There was no difference between the 1,25‐(OH)2D, and immunoreactive PTH (iPTH) levels of Paget's patients and control subjects. The percentage molar ratio of 1,25‐(OH)2D to 25‐OHD in untreated Paget's patients (0.157 ± 0.09%) was not significantly different from controls (0.124 ± 0.05%) despite lower 25‐OHD levels in Paget's patients. There was a significant inverse correlation between the severity of Paget's disease as measured by plasma alkaline phosphatase (AP) levels and 25‐OHD levels (r= 0.392,p<0.02); however, 24,25‐(OH)2D and 1,25‐(OH)2D levels were not correlated with AP. No correlation was found between any vitamin D metabolite and AP levels in control subjects.Three treatment groups of Paget's patients were studied: (1) oral EHDP treatment (up to 6 months), in which plasma corrected calcium (Cacorr) fell but serum ionized calcium (Ca2+) and plasma total calcium (Ca) remained unchanged. Plasma AP fell significantly with treatment, and serum 1,25‐(OH)2D levels increased significantly. The already low 24,25‐(OH2D levels (compared with control values) fell further with treatment. (2) Short‐term (CT) treatment (up to 18 months) showed a significant decrease in AP and Cacorrbut not in Ca2+or Ca. Again, serum 1,25‐(OH)2D levels increased significantly compared to pretreatment values, but 24,25‐(OH)2D levels were unchanged. (3) Long‐term CT treatment (between 20 months and 8 years), in which the only significant changes observed were a fall in AP and a rise in Ca. In all three treatment groups, serum iPTH, Ca2+, 25‐OHD, and plasma phosphate were unchanged with therapy.We conclude that Paget's disease is associated with alterations in vitamin D metabolite levels and that treatment with either CT or EHDP results in further changes in these levels, with no change in iPTH or Ca2+. Mediation by iPTH levels and the various indices of serum calcium appear unable to adequately explain these marked alterations in vitamin D metabolite levels. Thus a more extensive inv

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051105

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

年代:1990

数据来源: WILEY

摘要:

AbstractEarlier work from our laboratory demonstrated that heparin inhibits type I collagen and DNA synthesis in fetal rat calvariae in vitro. In this paper we have analyzed the structural features of heparin that determine its inhibitory effect on collagen synthesis. These experiments were performed using unmodified heparins and low‐molecular‐weight heparins from different manufacturers, nonheparin glycosaminoglycans, desulfated heparins, anticoagulant and nonanticoagulant heparin, and chemically defined heparin oligosaccharides. Low‐molecular‐weight heparin (Mr3700–5100) inhibited collagen synthesis, but oligosaccharides (disaccharides to decasaccharide,Mr665–3000) did not. The glycosaminoglycans chondroitin sulfate B, heparan sulfate, and hyaluronic acid did not alter collagen synthesis but dextran sulfate was as inhibitory as unmodified heparin. Nonanticoagulant as well as anticoagulant low‐molecular‐weight heparin fractions inhibited collagen synthesis. Modification of heparin by total desulfation, O‐desulfation, or N‐desulfation and re‐N‐acetylation resulted in the loss of inhibitory property, suggesting that the degree of sulfation contributed to heparin's inhibitory effect. Low‐molecular‐weight heparins from different manufacturers were just as inhibitory as native heparin on collagen synthesis. We therefore conclude that low‐molecular‐weight heparin compounds offer no protection against heparin‐induced osteoporosis. Our findings also suggest that the size and sulfation of a heparin‐derived oligosaccharide contribute to its ability to

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051106

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

年代:1990

数据来源: WILEY

摘要:

AbstractTrue calcium absorption was studied as a function of the size of the ingested load in healthy adult women, under meal conditions and at loads ranging from 15 to 500 mg calcium. Fractional absorption was highly inversely correlated with the logarithm of load (P<0.001). At the lowest loads, absorption averaged 64.0% and at the highest, 28.6%. The parameters of the best‐fit relationship permit reasonably precise calculation of the impact of various calcium dosing and dietary strategie

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051107

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

年代:1990

数据来源: WILEY

摘要:

AbstractCalcium absorption efficiency was measured two or three times each in 74 premenopausal and 142 postmenopausal women under conditions predicted to alter absorptive performance. A woman's absorptive consistency was evaluated across differing loads, differing intervals, and substances of differing intrinsic absorbability. In all these circumstances there was a statistically significant correlation between a woman's absorption under differing test situations accounting for up to 60% of the variance typically found in cross‐sectional studies. For example, when the same substance but at differing load levels was tested three times over an 8 week period, various coefficients of correlation ranged from + 0.773 to + 0.849 (P<0.001). Even over intervals as long as 5 years correlation of absorption fraction within individuals remained significant (r= +0.487,P<0.001

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051108

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe effects of progesterone on oophorectomy‐induced bone loss in aged rats were evaluated. Female rats aged 12 months were divided into three groups: (1) sham‐operated controls (SHAM); (2) oophorectomized (OVX); (3) OVX rats treated with progesterone (OVX + PROG). After 20 weeks the dry weight, bone ash, and calcium content of femur, tibia, and fourth lumbar vertebra were significantly lower in OVX than in sham rats. These reductions did not occur in OVX rats treated with PROG. There was no difference in the bone composition between the control and progesterone‐treated rats. Vertebral bone histomorphometry showed increased bone resorption as well as increased bone formation parameters in OVX rats. Progesterone treatment inhibited the increased resorption indices, but the bone formation remained elevated. The results indicate that progesterone therapy prevents the postovariectomy bone loss in aged rats. The protective effect of progesterone is mediated by inhibition of bone resorption while maintaining the increased bone formation. These findings suggest that progesterone alone may be a valuable agent for management of postmenopausal osteopo

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051109

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

年代:1990

数据来源: WILEY

摘要:

AbstractWe have shown previously that the decreased trabecular bone formation in osteoporotic postmenopausal women results from a reduced ability of osteoblastic cells to proliferate. In this study we have tested the possibility that bone cells from osteoporotic women with low bone formation have an abnormal responsiveness to hormonal or local mitogenic factors. Primary cultures of bone cells with osteoblastic characteristics were obtained by migration from the trabecular bone surface in osteoporotic postmenopausal women with high (n= 7) or low (n= 7) bone formation as evaluated histomorphometrically by the extent of double tetracycline‐labeled surface (DLS). Control bone cells were obtained under identical conditions from eight normal age‐matched postmenopausal women. Parameters of osteoblastic differentiation (alkaline phosphatase activity and osteocalcin production) were found to be normal and similar in bone cells from osteoporotic women with low or high DLS. In contrast, cell replication as evaluated by [3H]thymidine into DNA was 3.4‐fold lower in the low DLS group compared to the high DLS group, confirming our previous findings. Treatment of quiescent bone cells with TGF‐β (0.5–1 ng/ml) for 24 h significantly stimulated DNA synthesis in osteoblastic cells from normal women and in bone cells from osteoporotic patients with low or high DLS, indicating a normal responsiveness to TGF‐β in these patients. We have compared the effect of parathyroidhormone (PTH) on bone cells from normal and osteoporotic women. Basal cAMP levels and the cAMP accumulation in response to (1–34)‐hPTH were similar in bone cells from patients with low or high DLS and were not different from normal values. The responsiveness of bone cells from osteoporotic women to exogenous prostaglandin E2(PGE2) was also evaluated. PGE2(24 h) produced a dose‐related biphasic effect on DNA synthesis in bone cells from both normal and osteoporotic weomen. At low concentration (10−11M) PGE2increased DNA synthesis whereas at higher concentration (10−7M) it was inhibitory. cAMP production was increased by PGE2at doses that inhibited DNA synthesis. The responsiveness to PGE2was not different in normal bone cells and in cells from osteoporotic women with low and high DLS. These results indicate that the reduced bone cell proliferative capacity in osteoporotic postmenopausal women with low bone formation does not result from a lower than normal responsiveness

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051110

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe bone, liver, and kidney isozyme of alkaline phosphatase (ALP) has been measured in MG‐63 human osteosarcoma cells after treatment with ascorbic acid (AA) and/or 1,25‐dihydroxyvitamin D3[1,25‐(OH)2D3]. Both compounds were required to achieve maximum ALP activity. When grown in the absence of 1,25‐(OH)2D3cells had low basal ALP activity regardless of whether media contained AA. In AA‐free medium, 1,25‐(OH)2D3(10 nM) increased ALP activity fourfold. Addition of AA further increased levels of ALP activity induced by 1,25‐(OH)2D3to 10–15 times those found in ‐AA controls. The earliest effects of 1,25‐(OH)2D3were seen after 24–48 h, and ALP activity continued to increase for 6–8 days. AA and 1,25‐(OH)2D3had similar effects on ALP activity in ROS 17/2.8 rat osteosarcoma cells. In MG‐63 cells the effects of AA and 1,25‐(OH)2D3could not be simply explained by the ability of these compounds to inhibit cell growth because another mitotic inhibitor, hydroxyurea, had a minimal effect on ALP activity. 1,25‐(OH)2D3‐specific induction of ALP ± AA was totally blocked by inhibitors of protein and RNA synthesis. Maximal ALP induction was obtained when cells were plated at low density. Consistent with our previous report (Franceschi et al. 1988 J Biol Chem263:18938–18945), 1,25‐(OH)2D3rapidly stimulated type 1 collagen synthesis and acid‐precipitable hydroxyproline production in MG‐63 cells and this stimulation was further increased by AA. These results suggest that induction of the osteoblast marker, ALP, is directly or indirectly coupled to col

ISSN:0884-0431    

DOI:10.1002/jbmr.5650051111

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

年代:1990

数据来源: WILEY