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Hypoxia‐inducible factor 2α is a novel inhibitor of chondrocyte maturation
Author(s) -
Che Xiangguo,
Park NaRae,
Jin Xian,
Jung YounKwan,
Han MinSu,
Park Clara Yongjoo,
Chun JangSoo,
Kim SeongGon,
Jin Jingchun,
Kim HyunJu,
Lian Jane B.,
Stein Janet L.,
Stein Gary S.,
Choi JeYong
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30356
Subject(s) - chondrocyte , runx2 , microbiology and biotechnology , hypoxia inducible factors , downregulation and upregulation , mesenchymal stem cell , chemistry , cartilage , biology , transcription factor , anatomy , biochemistry , gene
Hypoxic environment is essential for chondrocyte maturation and longitudinal bone growth. Although hypoxia‐inducible factor 1 alpha (Hif‐1α) has been known as a key player for chondrocyte survival and function, the function of Hif‐2α in cartilage is mechanistically and clinically relevant but remains unknown. Here we demonstrated that Hif‐2α was a novel inhibitor of chondrocyte maturation through downregulation of Runx2 stability. Mechanistically, Hif‐2α binding to Runx2 inhibited chondrocyte maturation by Runx2 degradation through disrupting Runx2/Cbfβ complex formation. The Hif‐2α‐mediated‐Runx2 degradation could be rescued by Cbfβ transfection due to the increase of Runx2/Cbfβ complex formation. Consistently, mesenchymal cells derived from Hif‐2α heterozygous mice were more rapidly differentiated into hypertrophic chondrocytes than those of wild‐type mice in a micromass culture system. Collectively, these findings demonstrate that Hif‐2α is a novel inhibitor for chondrocyte maturation by disrupting Runx2/Cbfβ complex formation and consequential regulatory activity.