miR-29cb2 promotes angiogenesis and osteogenesis by inhibiting HIF-3α in bone

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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004221015741
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author 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
author_facet 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
author_sort Liping Ouyang
collection DOAJ
description 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
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spelling doaj.art-f30901f1868c4028bbdcd6bdf488291b2022-12-21T17:33:40ZengElsevieriScience2589-00422022-01-01251103604miR-29cb2 promotes angiogenesis and osteogenesis by inhibiting HIF-3α in boneLiping Ouyang0Yingxiao Sun1Dan Lv2Xiaochun Peng3Xiaoming Liu4Lei Ci5Guoning Zhang6Bo Yuan7Ling Li8Jian Fei9Jun Ma10Xuanyong Liu11Yun Liao12Department 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, ChinaDepartment of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, ChinaDepartment of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, ChinaDepartment of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University, Shanghai 200233, ChinaDepartment of Orthopedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, ChinaShanghai Engineering Research Center for Model Organisms, Shanghai Model Organisms Center, INC., Shanghai 201203, ChinaDepartment of Orthopedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, ChinaDepartment of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, ChinaDepartment of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, ChinaShanghai Engineering Research Center for Model Organisms, Shanghai Model Organisms Center, INC., Shanghai 201203, China; School of Life Science and Technology, Tongji University, Shanghai 200092, ChinaHongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China; Corresponding authorState 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 authorDepartment of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China; Corresponding authorSummary: 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 losshttp://www.sciencedirect.com/science/article/pii/S2589004221015741Molecular biologyDevelopmental biology
spellingShingle 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
miR-29cb2 promotes angiogenesis and osteogenesis by inhibiting HIF-3α in bone
iScience
Molecular biology
Developmental biology
title miR-29cb2 promotes angiogenesis and osteogenesis by inhibiting HIF-3α in bone
title_full miR-29cb2 promotes angiogenesis and osteogenesis by inhibiting HIF-3α in bone
title_fullStr miR-29cb2 promotes angiogenesis and osteogenesis by inhibiting HIF-3α in bone
title_full_unstemmed miR-29cb2 promotes angiogenesis and osteogenesis by inhibiting HIF-3α in bone
title_short miR-29cb2 promotes angiogenesis and osteogenesis by inhibiting HIF-3α in bone
title_sort mir 29cb2 promotes angiogenesis and osteogenesis by inhibiting hif 3α in bone
topic Molecular biology
Developmental biology
url http://www.sciencedirect.com/science/article/pii/S2589004221015741
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