| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
It has been generally accepted that most of the biological actions of vitamin D_3 are exerted by the vitamin D receptor (VDR)-mediated gene expression. In fact, bone formation was severely impaired in VDR null mutant mice). However, recent reports have been suggested that normalization of mineral ion homeostasis may prevent the development of osteomalacia and rickets morphologically in VDR null mutant mice. Here, we focused on the expression of osteogenic factors, such as osteocalcin and osteopontin, in femurs and lumber spines. Although mRNA expression of osteopontin, a functional but non-specific protein in bone, is activated by 1α, 25-dihydroxyvitamin D3 (1,25(OH)_2_3), mRNA expression of osteocalcin. a developmentally regulated bone-specific protein, is not, activated by 1,25(OH)_2_3 in mice. The differential effect of 1,25(OH)_2_3 on osteocalcin and osteopontin mRNA expression was investigated using VDR null mutant mice. We measured levels of osteocalcin and osteopontin mRNA expression in femurs and lumber spines of 3- and 7-week-old C57BL/6 strain mice of wild type and VDR null mutant. Femoral osteocalcin mRNA expression in 7-week-old VDR null mice was lower than that in the wild-type mice, whereas osteopontin mRNA expression in both mice was almost same. Lumbar osteopontin mRNA expression in the both mice was also almost the same. Bone mineral density (BMD) and mechanical bone strength (MBS) of femurs were extremely lower in VDR null mice. Compared with those in wild-type mice at 7 weeks. From these results, marked decreases of BMD and MBS in VDR null mice may not be due to reduced mRNA expression of osteocalcin and osteopontin. Therefore, the substitutive factors should be considered to regulate mRNA expression of osteogenic factors in the absence of VDR, although their contribution may not be enough for osteogenesis.
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