骨质疏松（OP）是导致老年患者骨折的最常见病因，其致残、致死率极高，已成为危害人类健康的严重公共卫生问题，但具体机制不清。HP1通过调控H3K9甲基化，在成骨分化中发挥关键作用。课题组前期发现HP1家族基因Cbx1、Cbx3、Cbx5在OP组织及成骨细胞中呈高表达，并伴随成骨分化其表达逐渐下调。下调Cbx1、Cbx3表达能显著促进成骨相关基因表达而促进骨骼矿化；下调Cbx5表达则明显抑制了成骨进程。下调HP1表达抑制了H3K9Me3的表达水平，且致使异染色质结构松弛。以上提示，HP1可通过H3K9甲基化，在表观水平调控成骨分化。本研究拟通过分子生物学及生物化学手段，深入探索HP1/H3K9Me3途径调控成骨的机制；通过构建小鼠OP模型，体内验证HP1/H3K9Me3途径对OP的调控作用。希望本研究的开展，能够阐明HP1/H3K9Me3途径调控成骨分化的具体机制，为OP提供新的临床解决途径。

Osteoporosis (OP) is the most common pathogeny leading to fractures in elder patients, incidence of lethality and disability is extremely high that it has become a serious public problem endangering human health, whereas mechanisms are unknown. Heterochromatin protein 1 (HP1) families play a vital role through regulating H3K9 methylation during osteoblastic differentiation. Our previous study revealed that HP1 families Cbx1, Cbx3 and Cbx5, are fold highly expressed in OP tissues and osteoblasts, meanwhile are down-regulated during osteoblastic differentiation. Knockdown of Cbx1 and Cbx3 expression enhanced related osteogenic genes expression and promoted bone mineralization; whereas knockdown of Cbx5 expression oppositely inhibited osteoblastic process. Down-regulated of HP1 inhibited H3K9Me3 protein expression, and additionally resulted in relaxation of heterochromatin. Above findings indicated, HP1 could regulate osteoblastic differentiation through H3K9 methylation at an epigenetic arena. This study intended to explore the mechanisms of HP1/H3K9Me3 pathway in regulating ossification by means of molecular biology and biochemistry, and was followed by in vivo study to further verify the regulatory role of HP1/H3K9Me3 pathway to OP in a mouse model. Hope this study will elucidate the deeply mechanisms of HP1/H3K9Me3 pathway in regulating ossification, thus provide new clinical approach to OP treatment.