Controlling hypoxia-inducible factor-2α is critical for maintaining bone homeostasis in mice

Controlling hypoxia-inducible factor-2α is critical

for maintaining bone homeostasis in mice

Sun Young Lee[1,2];Ka Hyon Park[1,2];Hyung-Gu Yu[2];Eunbyul Kook[2];Won-Hyun Song[2];Gyuseok Lee[2];Jeong-Tae Koh[1,2];Hong-In Shin[3];Je-Yong Choi[4];Yun Hyun Huh[5];Je-Hwang Ryu[1,2];;;;;

【期刊名称】《骨研究：英文》 【年(卷),期】2019(007)002

【摘要】Pathological bone loss is caused by an imbalance between bone formation and resorption.The bone microenvironments are hypoxic,and hypoxia-inducible factor (HIF) is known to play notable roles in bone remodeling.However,the relevant functions of HIF-2α are not well understood.Here,we have shown that HIF-2α deficiency in mice enhances bone mass through its effects on the differentiation of osteoblasts and osteoclasts.In vitro analyses revealed that HIF-2α inhibits osteoblast differentiation by targeting Twist2 and stimulates RANKL-induced

osteoclastogenesis

via

regulation

of

Traf6.In

addition,HIF-2α appears to contribute to the crosstalk between osteoblasts and osteoclasts by directly targeting RANKL in osteoprogenitor cells.Experiments performed with osteoblast- and osteoclast-specific conditional knockout mice supported a role of HIF-2α in this crosstalk.HIF-2α deficiency alleviated ovariectomy-induced bone loss in mice,and specific inhibition of HIF-2α with ZINC04179524