miR-29cb2 promotes angiogenesis and osteogenesis by inhibiting HIF-3α in bone
Liping Ouyang,
Yingxiao Sun,
Dan Lv,
Xiaochun Peng,
Xiaoming Liu,
Lei Ci,
Guoning Zhang,
Bo Yuan,
Ling Li,
Jian Fei,
Jun Ma,
Xuanyong Liu,
Yun Liao
Affiliations
Liping Ouyang
Department of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China; Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Yingxiao Sun
Department of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Dan Lv
Department of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Xiaochun Peng
Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China
Xiaoming Liu
Department of Orthopedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Lei Ci
Shanghai Engineering Research Center for Model Organisms, Shanghai Model Organisms Center, INC., Shanghai 201203, China
Guoning Zhang
Department of Orthopedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Bo Yuan
Department of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Ling Li
Department of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Jian Fei
Shanghai Engineering Research Center for Model Organisms, Shanghai Model Organisms Center, INC., Shanghai 201203, China; School of Life Science and Technology, Tongji University, Shanghai 200092, China
Jun Ma
Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China; Corresponding author
Xuanyong Liu
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China; School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; Corresponding author
Yun Liao
Department of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China; Corresponding author
Summary: Coordination between osteogenesis and angiogenesis is required for bone homeostasis. Here, we show that miR-29cb2 is a bone-specific miRNA and plays critical roles on angiogenesis-osteogenesis coupling during bone remodeling. Mice with deletion of miR-29cb2 exhibit osteopenic phenotypes and osteoblast impairment, accompanied by pronounced decreases in specific H vessels. The decrease in bone miR-29cb2 was associated with pathological ovariectomy stimuli. Mechanistically, hypoxia-inducible factor (HIF)-3α, as a target for miR-29cb2, inhibits HIF-1α activity by competitively bonding with HIF-1β. Notably, miR-29cb2 in peripheral blood (PB) nearly is undetectable in sham and significantly increases in ovariectomy mice. Further evaluation from osteoporosis patients demonstrates similar signatures. ROC analysis shows miR-29cb2 in PB has higher sensitivity and specificity for diagnosing osteoporosis when compared with four clinical biomarkers. Collectively, these findings reveal that miR-29cb2 is essential for bone remodeling by inhibiting HIF-3α and elevated bone-specific miR-29cb2 in PB, which may be a promising biomarker for bone loss
