MicroRNA-23/27基因簇在雌激素调控破骨细胞分化及骨吸收中的作用和分子机制研究

雌激素减少引起的破骨细胞分化及骨吸收增加是PMOP发生的重要机制之一。我们最近研究发现，雌激素能够明显上调破骨细胞前体细胞中microRNA-23/27基因簇的表达，而这一基因簇的高表达会导致破骨细胞分化和骨吸收减少。因此，推测雌激素可能通过诱导microRNA-23/27基因簇表达抑制破骨细胞的分化及功能。为进一步证实该推测并探索其具体的分子机制，本研究拟通过体内和体外实验、应用分子生物学及生物信息学技术、结合RNAi或过表达等干预手段，明确microRNA-23/27基因簇在雌激素调控破骨细胞分化及骨吸收中的作用、揭示microRNA-23/27基因簇的具体作用机制、初步确定雌激素对microRNA-23/27基因簇的调控方式。本研究结果将为完善PMOP的发病机理提供有效证据，并有望为临床治疗提供新的策略。

Estrogen deficiency is an important reason of osteoporosis in postmenopausal women. Researchers confirmed that osteoporosis can be produced by estrogen deficiency through increasing osteoclasts defferentiation and bone resorption. However, the exact mechanisms of estrogen impacting osteoclasts defferentiation and function are unclear. Recently, we found that microRNA-23/27 cluster expressions were significently up-regulated by estrogen and osteoclasts differentiation and function were inhibited by microRNA-23/27 cluster. Therefore, we speculated that microRNA-23/27 cluster may be involved in osteoclasts differentiation and founction regulated by estrogen. Molecular biology and bioinformatics technologys will be applied in vivo and vitro to further confirm speculation and to explore the mechanisms of estrogen-decreasing osteoclasts differentiation through microRNA-23/27 cluster. Furthremore, the way of microRNA-23/27 cluster rugulated by esrogen will be validated. This study provides an important theoretical basis for clarifying the etiology of postmenopausal osteoporosis and a new strategy for clinic treatment.