FBW7 regulates HIF-1α/VEGF pathway in the IL-1β induced chondrocytes degeneration

W.-J. Zhu, B.-Y. Chang, X.-F. Wang, Y.-F. Zang, Z.-X. Zheng, H.-J. Zhao, Q.-D. Cui

Department of Joint Trauma Surgery, Jiaozhou Central Hospital of Qingdao, Qingdao, China. cby5263128@163.com

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• Orthopedics

OBJECTIVE: The aim of the study was to observe the effect of F-box/WD repeat-containing protein 7 (FBW7) on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in chondrocytes (CHs) under IL-1β induced degeneration.

PATIENTS AND METHODS: We explored the levels of FBW7, HIF-1α, and VEGF in degenerated cartilage from osteoarthritis (OA) and chondrocytes (CHs) treated by IL-1β. Meanwhile, we regulated HIF-1α and FBW7 expression in IL-1β treated CHs and observed the effects FBW7 of the HIF-1α/VEGF pathway.

RESULTS: FBW7 expression was significantly decreased along with the increased HIF-1α and VEGF expression both in OA cartilage and IL-1β induced degenerated CHs. Additionally, suppression of HIF-1α decreased VEGF level, which contributed to the production of collagen II, aggrecan and SOX-9, and inhibited collagen I and Runx-2 expression. Furthermore, FBW7 suppressed HIF-1α/VEGF pathway and promoted the integration of collagen II, aggrecan, and SOX-9, but inhibited the collagen I and Runx-2 expression.

CONCLUSIONS: FBW7 negatively regulates HIF-1α/VEGF pathway and plays a protective role in the IL-1β induced CHs degeneration.

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