瘦素与雌激素对间充质干细胞的协同作用--绝经后骨质疏松症发病机制探讨

Objective: To study the influence and mechanism of leptin, estradiol, leptin and estradiol together on self-renewal capacity in bone marrow mesenchymal stem cells (BMSCs). Method: We stratifiedly randomized two-month-old female SD rats into bilateral ovariectomy (OVX) and sham group according to body weight. 14 weeks after the surgery, bone mineral density (BMD) were measured by dual energy X ray absorptiometry (DXA), seurm leptin and estradiol lever were examinated by Enzyme linked immunosorbent assay (ELISA) and radioimmunoassay respectively. We introduced CCK-8 to figure out the effect of leptin, estradiol, leptin plus estradiol on BMSCs proliferation, adopted qPCR to evaluate mRNA expression of cell cycle related gene, and introduced western blot to examine lever of phosphorylation and protein expression of Akt. Result: BMD of femoral head in OVX group was significantly reduced, and so dose the BMD of femoral shaft. The interaction between estrogen and leptin might had protective effect on mineral density of femoral head. After intervetion for 6 days, leptin but not estradiol can obviously promote proliferation of BMSCs. Leptin plus estradiol had synergistic effect to encourage BMSCs proliferation. mRNA expression of Akt downstream moleculors (cyclinD1, cyclinD2 and PCNA) was elevated in leptin treatment group. Further western blot detection found that both estrodiol and leptin promoting Akt phosphorylation in BMSCs in every time point And the lever of Akt phosphorylation demonstrated time dependent effect under adiministration of both two hormones. Conclusion: Leptin can stimulate proliferarion of BMSCs in vitro. Leptin and estradiol have synergitic effect in promoting self-renewal capacity of BMSCs through Akt signal pathway.