1. Hypoxia-inducible factor 2α is a novel inhibitor of chondrocyte maturation.
- Author
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Che X, Park NR, Jin X, Jung YK, Han MS, Park CY, Chun JS, Kim SG, Jin J, Kim HJ, Lian JB, Stein JL, Stein GS, and Choi JY
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Cell Hypoxia, Cell Line, Tumor, Core Binding Factor Alpha 1 Subunit genetics, Core Binding Factor Alpha 1 Subunit metabolism, Core Binding Factor beta Subunit genetics, Core Binding Factor beta Subunit metabolism, Mice, Knockout, Protein Stability, Proteolysis, Rats, Ubiquitination, Mice, Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Differentiation, Chondrocytes metabolism, Chondrogenesis
- Abstract
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., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
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