|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1993 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1992 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Vitamin D receptor(VDR) is a nuclear transcription factor which binds to vitamin D response element(VDRE) of human osteocalcin gene and regulates expression. Human VDR defect shouws clinical heterogeneity among patients with the same point mutation their VDR gene. In addition, rickets did not recur after the cessation of therapy during 6 to 24 years of follow up. To elucidate these clinical findings, the complex formations of VDRE and nuclear extracts of cultured skin fibroblasts treated with 1,25-dihydroxyvitamin D_3(1,25(OH)_2D_3), retinoic acid(RA) and/or triiodothyronine(T3) were investigated as a molecular parameters of transcriptional activity. The complex formation in control cells was increased by the treatment of either 0.1nM, 1nM, 10nM 1,25(OH)_2D_3, 100nM RA or 100nM T3, however additive effect of these combinations was not found. In patient's cells, either 1,25(OH)_2D_3, RA or T3 increased the complex formation, while neither combination also additively stimulated. These results indicated that 1,25(OH)_2D_3. RA and T3 had some role in the regulation of bone remodeling through modulating osteocalcin expression. Therefore, clinical observation in patients with VDR defect might be at least patrly explained by overlapping control in the regulation of osteocalcin expession.