维生素D3调节人骨肉瘤细胞系细胞增殖分化的分子机制

The biologically active metabolite of vitamin D, 1a,25-dihydroxyvi-tamin D3 [1,25(OH)2 D3], exerts profound effects on cell proliferation, differentiation, and immunomodulation, in addition to its classical effects on bone mineralization and calcium-phosphorus homeostasis. Taking the human osteosarcoma cell line (HOS-8603) as a cell model, we first confirmed that 1,25(OH)2 D3 exerted its regulatory effect on proliferation and differentiation of HOS-8603 cells and VDR, which possess hormone-dependant transactivation function, did exsist in HOS-8603 cell. After the blockage of expression of VDR by using the technology of antisense nucleotide, the inhibitory effect of 1,25(OH)2 D3 on the proliferation of HOS-8603 cells and the induction of differentiation of HOS-8603 cells were obviously weakened. This result demonstrated that VDR participate in the regulation of proliferation and differentiation of HOS-8603 cells. Further studies shew that the expression of p21, an endogenous target gene of VDR, was markedly induced by 1,25(OH)2 D3. and the stable overexpression of p21 in HOS-8603 cell depressed the proliferation of cells obviously. These results indicated that the induction of p21 expression is one of the regulatory mechanism of 1,25(OH)2 D3 on proliferation and differentiation of HOS-8603 cell. In this study, we have explored the molecular mechanism of the effects of 1,25(OH)2 D3 on proliferation and differentiation of human osteosarcoma cell line. And meanwhile, we have found some interesting questions. All of these are beneficial to our further study of the mechanism of the effects of 1,25(OH)2 D3 on proliferation and differentiation of HOS-8603 cells.

从1，25（OH）2D3受体（VDR）及其靶基因（P21）两个水平上阐明激素调节人骨肉瘤细胞系（HOS-8603）增殖分化的分子机制：用VDR反义mRNA表达载体转梁HOS-8603，筛选出稳定表锟寺。鄄?，25（OH）2D3对转染细胞的影响，以确定内源性VDR在介导激素作用中的决定性作用。观察1，25（OH）2D3对P21表达的诱导作用，构建P21真核表达载体，分析P21过度泶锸倍訦OS-8603细胞表型的影响。