The dichotomy in the effects of 1,25 dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 on bone γ-carboxyglutamic acid-containing protein in serum and bone in vitamin D-deficient rats |
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Authors: | Shlomo Wientroub Paul A Price A H Reddi |
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Institution: | (1) Department of Orthopedic Surgery, Tel-Aviv Medical Center, Sackler School of Medicine, Tel-Aviv University, 6 Weizman St., 64239 Tel-Aviv, Israel;(2) Department of Biology (B-022), University of California, San Diego, 92093 La Jolla, California, USA;(3) Bone Cell Biology Section, Mineralized Tissue Research Branch National Institute of Dental Research, NIH, 20892 Bethesda, Maryland, USA |
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Abstract: | Summary Vitamin D-deficient, second generation, rachitic rats showed significant decrease in bone Gla protein (BGP) levels in circulation
and in the skeleton. 1,25 dehydroxyvitamin D3 (1,25 (OH)2D3) exhibited the most potent influence on serum BGP levels in a dose-dependent manner. At a dose 25 ng/100 g body weight 1,25
(OH)2D3 showed a cumulative effect, i.e., the longer the treatment, the more circulating BGP was detected 24,25 dehydroxyvitamin
D3 (24,25(OH)2D3) at the same doses did not show similar effect on the serum BGP levels, regardless of the serum calcium levels. Bone BGP
levels assayed at various sites representing endochondral and intramenbranous ossification demonstrated an opposite pattern.
1,25(OH)2D3 administration was not sufficient to restore bone BGP levels to normalcy, whereas in animals treated with 24,25(OH)2D3 bone BGP and calcium levels were significantly higher than control (Vitamin D3-repleted) levels. The present results can be explained by the dual action of 1,25 (OH)2D3 on both synthesis and release of BGP by bone turnover, whereas 24,25 (OH)2D3 stimulates synthesis and accumulation of BGP in bone. These observations imply that caution is required in the interpretation
of clinical data based solely on serum BGP determination. |
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Keywords: | Bone Gla Protein 1 25 Dihydroxyvitamin D3 24 25 Dihydroxyvitamin D3 Rickets Mineralization |
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