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

Abstract

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