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1. |
Perspectives: The genomic mechanism of action of 1,25‐dihydroxyvitamin D3 |
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Journal of Bone and Mineral Research,
Volume 6,
Issue 10,
1991,
Page 1021-1027
Keiichi Ozono,
Teruki Sone,
J. Wesley Pike,
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ISSN:0884-0431
DOI:10.1002/jbmr.5650061002
出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
年代:1991
数据来源: WILEY
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2. |
Effect of caffeine on parameters of osteoblast growth and differentiation of a mineralized extracellular matrix in vitro |
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Journal of Bone and Mineral Research,
Volume 6,
Issue 10,
1991,
Page 1029-1036
Melissa S. Tassinari,
Louis C. Gerstenfeld,
Gary S. Stein,
Jane B. Lian,
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摘要:
AbstractThe effects of caffeine exposure on bone formation were examined using a chick osteoblast culture system. Secondary cultures of normal diploid osteoblasts were exposed to chronic doses of 0, 0.1, 0.2, or 0.4 mM caffeine beginning on day 0 through day 28. Neither the rate of cell proliferation nor cell number, as measured by total DNA, was decreased for any of the doses examined. In contrast, osteocalcin levels, alkaline phosphatase activity, and total calcium levels showed a dose‐related decrease in cultures treated with caffeine. These parameters were significantly decreased at the highest dose of 0.4 mM. The reduction in total protein levels ranged rom 29 to 66% of control values and was independent of dose. In contrast, total collagen levels were more affected by the dose of caffeine used. Inhibition of collagen levels was most apparent on days 17 and 21, time points during the period of active formation of the matrix immediately preceding the deposition of mineral. By day 28 collagen levels in cultures exposed to the lower doses of caffeine had returned to control levels, and only the cultures exposed to the highest dose (0.4 mM) remained significantly inhibited with respect to both collagen and mineral. Histochemically, alkaline phosphatase and mineral staining of day 28 cultures mirrored the biochemical events with the 0.4 mM caffeine exposure. The results indicate that one of the effects of caffeine on bone development is to inhibit the formation of a competent extracellular matrix during the osteoblast differentiation sequence, which results in the inhibition of mineralization analogous to the delayed ossification observed in fetal animals after prenatal caffeine exposur
ISSN:0884-0431
DOI:10.1002/jbmr.5650061003
出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
年代:1991
数据来源: WILEY
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3. |
Effects of potassium peroxydiphosphate on bone resorption |
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Journal of Bone and Mineral Research,
Volume 6,
Issue 10,
1991,
Page 1037-1042
Abdul Gaffar,
Cynthia B. Alander,
Lawrence G. Raisz,
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摘要:
AbstractPotassium peroxydiphosphate (KPDP) is a slowly hydrolyzed pyrophosphate analog that can release hydrogen peroxide during hydrolysis. We tested its effects on the resorption of cultured fetal rat long bones as measured by the release of previously incorporated45Ca, both by direct addition of KPDP to the medium and after preincubation of KPDP with large‐molecular‐weight resorbing factors followed by dialysis to reduce the KPDP concentration. With direct addition, KPDP at a concentration of 1 mM could inhibit the resortive response to bacterial lipopolysaccharide (LPS), parathyroid hormone (PTH), prostaglandin E2(PGE2), and mouse recombinant interleukin‐1 (mrIL‐1). The response to LPS was partially inhibited at 0.3 mM KPDP. Control resorption in the absence of stimulators was also inhibited. Potassium pyrophosphate at 1 mM was less effective as an inhibitor of bone resorption. The inhibitory effects of KPDP did not appear to be due entirely to nonspecific toxicity since partial recovery occurred after it was removed. There was no significant decrease in [3H]thymidine or [3H]proline incorporation into bones incubated with KPDP at 1 mM for 5 days, but [3H]proline incorporation was decreased at 24 h, suggesting that KPDP may have a general inhibitory effect on bone cells. When media with and without stimulators of resorption were incubated overnight at 4°C with KPDP at 5.8 mM and then dialyzed to bring the concentration to below 0.3 mM, the bone‐resorbing activity of PTH, LPS, and mrIL‐1 was completely lost. This may have been due to the slow release of hydrogen peroxide; however, preincubation with equimolar concentrations of H2O3caused only partial inactivation of PTH and LPS. Finally, 3% KPDP applied topically in hamsters reduced alveolar bone resorption, indicating that it could interact directly with local pathogenetic factors in vivo. These results indicate that KPDP may be a useful inhibitor of bone resorption. High concentrations of KPDP are required, but it is biodegradable to the normal body constituents,
ISSN:0884-0431
DOI:10.1002/jbmr.5650061004
出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
年代:1991
数据来源: WILEY
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4. |
Bone mass is related to creatinine clearance in normal elderly women |
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Journal of Bone and Mineral Research,
Volume 6,
Issue 10,
1991,
Page 1043-1050
Edmund R. Yendt,
Moussa Cohanim,
Stanley Jarzylo,
Glenville Jones,
Gilbert Rosenberg,
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摘要:
AbstractWe determined the relationship between bone mass and age, anthropometric variables, creatinine clearance (Ccr), and serum and urine biochemical variables in 77 normal white women (aged 41–86, mean = 67) living in their own homes. A total of 74 women were postmenopausal. Skeletal status was assessed in all subjects by x‐rays of the hand with measurement of the mean combined cortical thickness (CCT) of the second metacarpal bones. In 53 women, bone mineral content of the radial shaft (RMBC) was also measured by single‐photon absorptiometry (SPA) and lumbar bone mineral density (LBMD) was measured by dual‐photon absorptiometry (DPA). Serum and urine biochemical variables were measured under standardized conditions on the sixth and seventh days of a controlled diet. There was a strong positive correlation between Ccr and bone mass. Although our subjects showed the expected linear decline in Ccr with age, we found that the relationship between Ccr and bone mass in the radius and lumbar spine was independent of age. On the other hand, the relationship between Ccr and CCT was not independent of age. We concluded that the relationship between Ccr and lumbar and radial bone mass is probably indicative of a relationship between glomerular filtration rate and bone mass, although this requires validation with a noncreatinine method for measurement of glomerular filtration rate. Age per se does not appear to be a cause of declining lumbar bone mass after the me
ISSN:0884-0431
DOI:10.1002/jbmr.5650061005
出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
年代:1991
数据来源: WILEY
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5. |
Vitamin D analogs with low affinity for the vitamin D binding protein: Enhanced in vitro and decreased in vivo activity |
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Journal of Bone and Mineral Research,
Volume 6,
Issue 10,
1991,
Page 1051-1057
Roger Bouillon,
Katrien Allewaert,
Da Zhen Xiang,
Biauw Keng Tan,
Hugo van Baelen,
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摘要:
AbstractThe affinity of 1α,25‐dihydroxyvitamin D3[1α,25‐(OH)2D3] and analogs with side‐chain modifications [MC 903 or calcipotriol, MC 1147 or 24,24‐dihomo‐1α,25‐(OH)2D3and 1,25‐(OH)2‐16ene‐23yne‐D3] for the vitamin D receptor and the serum vitamin D binding protein (DBP) were compared. The affinity of MC 903 for the receptor from chick and rat duodenum or from human peripheral blood mononuclear cells or HL‐60 cells varied between 60 and 100% relative to the affinity of 1,25‐(OH)2D3. The relative affinity of 1,25‐(OH)2‐16ene‐23yne‐D3and MC 1147 varied for the same receptors between 45–70 and 3.5–25%, respectively. The relative affinity of MC 903 for human DBP was 30‐fold decreased, whereas the two other analogs did not bind to DBP at all even in more than 1000‐fold excess. The in vitro biologic activity of 1α,25‐(OH)2D3on phytohemagglutinin‐stimulated normal human lymphocyte proliferation was markedly inhibited by the addition of physiologic amounts of DBP to the cell culture medium. No such inhibition was observed when MC 903 or 1147 was evaluated similarly. DBP therefore reversed the rank order of the in vitro potency of these analogs. Intramuscular injections for 10 consecutive days to vitamin D‐deficient chicks demonstrated a ≥ 100‐fold lower biologic activity of MC 903, MC 1147, and 1,25‐(OH)2‐16ene‐23yne‐D3compared to that of 1α,25‐(OH)2D3as evaluated by serum calcium and osteocalcin concentrations, as well as by duodenal calbindin D28Kand bone calcium content. We conclude that the biologic activity of vitamin D metabolites and analogs depends on their affinity for the vitamin D receptor as well as their affinity for DBP. Analogs with a low DBP but good receptor binding properties display low in vivo biologic activity on calcium and b
ISSN:0884-0431
DOI:10.1002/jbmr.5650061006
出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
年代:1991
数据来源: WILEY
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6. |
Osteonectin is an α‐granule component involved with thrombospondin in platelet aggregation |
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Journal of Bone and Mineral Research,
Volume 6,
Issue 10,
1991,
Page 1059-1070
Philippe Clezardin,
Luc Malaval,
Marie‐Christine Trzeciak,
Josette Guichard,
Thomas Lecompte,
Marie‐Christine Morel,
Marc Dechavanne,
Janine Breton‐Gorius,
Pierre D. Delmas,
Cécile Kaplan,
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摘要:
AbstractWe previously showed that thrombospondin, a major α‐granule glycoprotein of human platelets, forms a specific complex with osteonectin, a phosphoglycoprotein originally described in bone that is also present in human platelets. The storage organelles and the function of osteonectin in platelets are still unknown. In this study, using electron microscopy in combination with immunogold staining, osteonectin was located within the major storage organelle for platelet‐secreted proteins, the α‐granules. Furthermore, osteonectin was qualitatively and quantitatively assessed by studying normal platelets and the platelets from a patient with gray platelet syndrome. Gray platelet syndrome is a rare congenital bleeding disorder characterized by a selective deficiency in morphologically recognizable platelet α‐granules and in the α‐granule secretory proteins. Binding of an iodinated antiosteonectin monoclonal antibody to gray platelet proteins transferred to nitrocellulose from SDS‐polyacrylamide gels showed no band corresponding to osteonectin compared to control platelets. Using a polyclonal antiosteonectin antibody‐based radioimmunoassay, gray platelets contained 0.2 ± 0.03 ng osteonectin per 106platelets, which is only 20% of the normal platelet content of osteonectin (0.93 ± 0.16 ng per 106platelets). Study of the localization of osteonectin to the surface of human platelets demonstrated that a radioiodinated antiosteonectin polyclonal antibody bound specifically to thrombin‐stimulated platelets but not to resting platelets. Binding was concentration‐dependent, saturable (1710 ± 453 binding sites per platelet,Kd= 1 μM), and inhibited by an excess of cold antiosteonectin polyclonal antibody. No binding was observed on the surface of thrombin‐stimulated gray platelets. To gain further insights into the role of osteonectin released from activated platelets, the effect of an antiosteonectin polyclonal antibody was tested on the aggregation of washed platelets. F(ab′)2fragments from the antiosteonectin polyclonal antibody inhibited in a dose‐dependent manner the aggregation of collagen‐stimulated, washed human platelets without affecting collagen‐induced platelet serotonin release. To characterize the mechanism through which antiosteonectin F(ab′)2fragments inhibit platelet aggregation, the expression of endogenous thrombospondin (TSP) on the surface of thrombin‐activated platelets was studied using125I‐labeled anti‐TSP monoclonal antibody P10. The endogenous surface expression of TSP to thrombin‐stimulated platelets was significantly inhibited in the presence of antiosteonectin F(ab′)2fragments (6286 ± 2065 molecules of P10 per platelet) compared to 11,230 ± 766 molecules of P10 per platelet in the presence of nonimmune F(ab′)2fragments. This inhibitory effect of antiosteonectin F(ab′)2fragments on the surface expression of endogenous TSP was not mediated by interference with binding of monoclonal antibody P10 to TSP as judged by enzyme‐linked immunosorbent assay. In summary, these results demonstrate that osteonectin is an α‐granule component that, by binding on the surface of activated platelets, is involved with TSP in the sec
ISSN:0884-0431
DOI:10.1002/jbmr.5650061007
出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
年代:1991
数据来源: WILEY
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7. |
Preexisting bone loss associated with ovariectomy in rats is reversed by parathyroid hormone |
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Journal of Bone and Mineral Research,
Volume 6,
Issue 10,
1991,
Page 1071-1080
Chung C. Liu,
Dike N. Kalu,
Elena Salerno,
Rosanno Echon,
Bruce W. Hollis,
Michelle Ray,
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摘要:
AbstractPrevious studies have demonstrated that when parathyroid hormone (PTH) administration to rats is started immediately following ovariectomy, it prevents bone loss due to ovarian hormone deficiency. In this study, we examined whether bone loss induced by ovariectomy could be reversed by pasrathyroid hormone if hormone therapy is started after the bone loss had already occurred. In the first experiment, two groups of animals were ovariectomized or sham operated, killed after 40 days, and their bones examined to ensure that bone loss occurred. In the second experiment, three groups of rats were studied. Group 1 rats were sham operated, and rats in groups 2 and 3 were ovariectomized. Each rat in group 3 received a single subcutaneous injection of 8 μg parathyroid hormone [hPTH‐(1–34); Bachem, CA] per 100 g body weight per day, starting 40 days following ovariectomy. Rats in groups 1 and 2 received solvent vehicle, and all animals were sacrificed on day 60. Ovariectomized rats had lost an appreciable amount of bone 40 days after surgery, as indicated by a significant decrease in femoral and vertebral densities and calcium and an over 55% loss of cancellous bone in the tibial metaphysis. The loss of bone was reversed by intermittent PTH administration. Increased cancellous bone in the parathyroid hormone‐treated ovariectomized rats was associated with increased trabecular osteoblasts, decreased trabecular osteoclasts, and increased serum osteocalcin and urinary hydroxyproline. Our findings indicate that parathyroid hormone can substantially augment bone mass after the loss due to ovarian hormone deficiency has already occurred. The hormone caused positive bone balance in vivo in ovarian hormone‐deficient animals by increasing bone formation and decreasing bone re
ISSN:0884-0431
DOI:10.1002/jbmr.5650061008
出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
年代:1991
数据来源: WILEY
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8. |
Tissue and urokinase plasminogen activators in bone tissue and their regulation by parathyroid hormone |
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Journal of Bone and Mineral Research,
Volume 6,
Issue 10,
1991,
Page 1081-1090
Gaetane Leloup,
Chantal Peeters‐Joris,
Jean‐Marie Delaisse,
Ghislain Opdenakker,
Gilbert Vaes,
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摘要:
AbstractThe identification of the plasminogen activator (PA) types present in bone and the regulation of their activity by parathyroid hormone (PTH) were investigated in cultures of fetal mouse calvariae with the use of either a chromogenic substrate or a zymographic assay. PA was detected essentially in the tissue extracts of the explanted bones, with only 1–2% of the total activity released in the surrounding culture media. From their electrophoretic behavior compared to PAs of other mouse tissues and from their response to a specific antibody raised against the tissue type PA (tPA), two major molecular species, of 70 and 48 kD were identified as tPA and urokinase (uPA), respectively, a third minor species of 105 kD being likely to correspond to complexes between tPA and an inhibitor; the culture fluids, moreover, contained enzymatically active degradation products of uPA of 42 and 29 kD. The PA activity of the bone extracts was only minimally affected by the addition of fibrinogen fragments to the chromogenic assays. PTH induced bone resorption and stimulated in parallel the accumulation of PA in the tissue; other bone‐resorbing agents, 1,25‐dihydroxyvitamin D, and prostaglandin E2, had similar effects. Densitometric scanning of the zymograms of the bone extracts indicated that PTH stimulated only the production of tPA and had no effect on that of uPA. However, PTH also enhanced the release of uPA (both the 48 kD and the 29 kD forms) from the bones into the media. Although inhibiting bone resorption, calcitonin had no effect on the PTH‐induced accumulation of PA in bone or on the release of tPA, but it prevented the PTH‐induced accumulation of 29 kD uPA in the culture fluids. Thus these studies support the view that tPA and possibly also uPA may have a role in the physiology of bone; the nature of this role remains to be elucidated
ISSN:0884-0431
DOI:10.1002/jbmr.5650061009
出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
年代:1991
数据来源: WILEY
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9. |
Inhibition of bone resorption by a monoclonal antibody that reacts with a 150 kD membrane protein in chicken osteoclasts |
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Journal of Bone and Mineral Research,
Volume 6,
Issue 10,
1991,
Page 1091-1097
Teuvo A. Hentunen,
Päivi T. Lakkakorpi,
Timo Rautiala,
H. Kalervo Väänanen,
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摘要:
AbstractBone resorption is a multistep process that includes the maturation of osteoclast precursors, the special attachment of fully differentiated osteoclasts to mineralized bone surface, and the dissolution of inorganic mineral, as well as the breakdown of organic matrix. We have produced a large panel of monoclonal antibodies directed against chicken osteoclasts to obtain specific probes for studying the function of osteoclasts. One of our antibodies, K20, inhibited bone resorption of isolated osteoclasts almost completely. Several pieces of evidence suggested that the antigen detected by this antibody was located in the plasma membrane of the osteoclast. In western blot analysis K20 antibody specifically recognized a 150 kD protein in the medullary bone microsome fraction under reducing and nonreducing conditions. In addition to osteoclasts and some bone and bone marrow mononuclear cells, a positive immunoreaction was seen in the kidney tubules. These data suggest that monoclonal antibody K20 reacts with an osteoclast surface antigen that is functionally important in bone resorption.
ISSN:0884-0431
DOI:10.1002/jbmr.5650061010
出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
年代:1991
数据来源: WILEY
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10. |
Stimulation of 1,25‐dihydroxyvitamin D3receptor gene expression in cultured cells by serum and growth factors |
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Journal of Bone and Mineral Research,
Volume 6,
Issue 10,
1991,
Page 1099-1107
Aruna V. Krishnan,
David Feldman,
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摘要:
AbstractThe abundance of 1,25‐dihydroxyvitamin D3receptors (VDR) in bone cells has been shown to vary in direct relation to the rate of cell proliferation. In this study we further explored this upregulation of VDR as it relates to the mitogenic response using NIH‐3T3 mouse fibroblasts and MCF‐7 human breast cancer cells as model systems. Serum and growth factors, such as EGF, high concentrations of insulin (2 μM), and IGF‐I, were mitogenic and stimulated the proliferation of both cells types. These factors also caused significant increases in VDR levels as measured by ligand binding assays, which preceded the rise in cell proliferation rate measured by [3H]thymidine incorporation. Serum and growth factors increased the abundance of VDR but did not affect the concentrations of other steroid receptors in MCF‐7 cells. Mouse cells have been reported to have several VDR mRNA transcripts. Our northern blot analysis revealed three mRNA species at approximately 7.5, 4.4, and 3 kb of which the 4.4 kb species was the most prominent and the 7.5 kb the least. Serum and growth factor stimulation of quiescent 3T3 cells led to significant increases in all the transcripts, suggesting that the upregulation occurs at the level of VDR mRNA expression. A time course analysis of serum stimulation in 3T3 cells showed that the mRNA species reached peak levels 4 h after serum addition. When serum stimulation was carried out in the presence of the protein synthesis inhibitor cycloheximide, the 3 kb transcript as well as the 7.5 kb transcript were superinduced but the stimulation of the 4.4 kb transcript was inhibited. Hydroxyurea (an inhibitor of DNA synthesis) and colchicine (a microtubule disruptive agent) had no effect on serum stimulation of the mRNA species, indicating that the enhanced expression of the VDR gene is not dependent upon theS,G2, orMphase of the cell cycle. The results suggest that the VDR gene appears to be one of a set of early genes activated when quiescent cells are stimulated by a mitoge
ISSN:0884-0431
DOI:10.1002/jbmr.5650061011
出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
年代:1991
数据来源: WILEY
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