抑制剂BYL719防治卵巢切除致骨质疏松症的研究

Inhibitor BYL719 Prevented OVX-induced Osteoporosis

目的 PI3K信号通路在破骨细胞前体细胞增殖、破骨细胞分化中均发挥重要功能。BYL719是经典的PI3K通路抑制剂,但其对骨代谢的影响,目前未见报道。方法通过构建卵巢切除后小鼠骨质疏松症模型,运用microCT进行骨组织形态学分析,研究BYL719对骨质疏松症的治疗作用。在此基础上,通过体外研究BYL719对破骨细胞前体细胞活性、破骨细胞分化、破骨细胞特异性基因表达以及破骨细胞骨吸收功能,明确BYL719对破骨细胞的功能。结果 BYL719在5 mg/kg和10 mg/kg浓度下,均可有效防治小鼠卵巢切除导致的骨丢失,可以抑制破骨细胞前体细胞活性,抑制破骨细胞分化以及破骨细胞特异基因表达。结论 PI3K-mTOR抑制剂BYL719可通过影响破骨细胞前体细胞活性、破骨细胞分化,最终达到治疗骨质疏松症的作用。

Objective PI3K signaling pathway plays a pivotal role in osteoclast precursor proliferation, os-teoclast differentiation. In addition, PI3K - mTOR specific inhibitor BYL719 hasnt been shown to affect bone me-tabolism. Methods In this study, we generated OVX - induced osteoporosis mice model and administrated 5 mg/kg and 10 mg/kg BYL719 in these mice. In addition, the effect of BYL719 on osteoclast precursor cell prolif-eration ,osteoclast differentiation, osteoclast specific gene expression and bone - resorption was investigated. Re-sults Both low and high dose BYL719 prevented OVX - induced osteoporosis, which can inhibit osteoclast precur-sor cell proliferation, osteoclast differentiation and gene expression. Conclusion PI3K - mTOR specific inhibitor BYL719 can prevent osteoporosis by inhibiting osteoclast precursor proliferation and osteoclast differentiation, indi-cating BYL719 as a potential candidate for the treatment of osteoporosis.