Hypoxia-inducible factor 2α is a novel inhibitor of chondrocyte maturation.
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.
['Che|Xiangguo|X|', 'Park|Na-Rae|NR|', 'Jin|Xian|X|', 'Jung|Youn-Kwan|YK|', 'Han|Min-Su|MS|', 'Park|Clara Yongjoo|CY|', 'Chun|Jang-Soo|JS|', 'Kim|Seong-Gon|SG|', 'Jin|Jingchun|J|', 'Kim|Hyun-Ju|HJ|0000-0002-5836-5841', 'Lian|Jane B|JB|', 'Stein|Janet L|JL|', 'Stein|Gary S|GS|', 'Choi|Je-Yong|JY|0000-0002-5057-8842']
D000818:Animals D051792:Basic Helix-Loop-Helix Transcription Factors D002454:Cell Differentiation D015687:Cell Hypoxia D045744:Cell Line, Tumor D019902:Chondrocytes D020219:Chondrogenesis D050659:Core Binding Factor Alpha 1 Subunit D050658:Core Binding Factor beta Subunit D018345:Mice, Knockout D055550:Protein Stability D059748:Proteolysis D051381:Rats D054875:Ubiquitination
chondrocyte maturation Hif-2α Runx2 Cbfβ Proteasomal degradation