Effect of Raloxifene on The Proliferation 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 from a switch of cell differentiation faxoring adipogenesis. Raloxifene, selective estrogen receptor modulator, prevent bone loss. Although it is largely used for the treatment of osteoporosis, the mechani는 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 the treatment agter this period the animals were divided into three experimental groups consisting of sham poerated(CON), Ovariectomy(OVX) and OVX-Raloxifene-treated rats(OVX-Ral) all animals received daily treatment of raloxifene 1mg/kg or placebo for 12weeks. OVX and OVX-Ral were compared with the CON group and were assessed for the alteration of these cell's proliferation and differentiation. The proliferation of stromal stem cells was measured by CFU-F assay. CFU-F count were not different among 3 groups. But Alkaline phosphatase(ALP)-positive colony count was decreased in bone marrow stromal cells derived form OVX group, was increased in OVX-Ral group. Differentiation of bone marrow stromal cell were assessed in vitro. Marrow stromal cells underwent differentiation in a osteogenic medium containing dexamethasone, ascorbic acid, glycerophsphate. In cells of OVX-Ral group, alkaline phosphatase activity and nodule formation were increased compared with one of OVX. The mRNA expression of ALP, osteocalcin were dccreased in OVX, but maintained in OVX-Ral. During the adipogenic differentiation, m굼 expression of PPAR gamma, FAS of OVX-Ral were decreased than those of OVX group. Oil-red O stains showed similar findings. In conclusion,