Effect of Raloxifene on Prolifertion and Differentiation of Bone Marrow Stromal Stem Cells in Ovariectomized Rats

초록

Since osteoblast and adipocytes originate from a common mesencymal precursor cell, it has been proposed that osteoporosis might in part result form a switch of cell differentiation favoring adipogenesis. Raloxifene, selective estrogen receptor modulator, prevent bone loss. Although it is largely used for the treatment of osteoporosis, the mechanisms by which this compound modulate bone cells are poorly understood. So, We used a rat model in which estrogen depletion was established for a period of 1 months before treatment After this period the animals were divided into three experimental groups consisting of sham operated(CON), Ovariectomy(OVX) and OVX-Raloxifene-treated rats(OVX-Ral). All animals received daily treatment of raloxifene or placebo for 12 weeks. OVX and OVX-treated rat were compared with CON group and assessed for the alteration of these cell’s differentiation. The proliferation of stromal stem cells was measured by CFU-F assay in vitro. CFU-F count were not different among 3 groups. Alkaline phosphatase positive colonies of ovariectomized rats with raloxifene were significant increase than those of OVX rats. The mineralization counts of OVX-Ral were siginificantly increase than those of OVX group. Marrow stromal cells undergo differentiation in a osteogenic medium containing fetal bovine serum, ascorbic acid, b-glycerophsphate. Alkaline phosphatase activity increased in OVX-Ral. Raloxifene increased alkaline phosphatase activity and nodule formation and stimulated messenger RNA(mRNA) expression of ALP, Adipocytic differentiation observed in the presence of the adipogenic media. In conclusion, osteogenic differentiation of mesenchymal stem cells were enhanced after treated with raloxifene Out results indicate that raloxifene inhibit adipogenesis, which might explain the clinical observation that raloxifene treatment decrease fracture incidence.