ZEB2 knockdown inhibits interleukin-1β-induced cartilage degradation and inflammatory response through the Wnt/β-catenin pathway in human chondrocytes.

Abstract

Objective: Osteoarthritis (OA) is a degenerative disease of the joints characterized by inflammation and cartilage degeneration. Zinc finger E-box binding homeobox 2 (ZEB2) contains various function domains that interact with multiple transcription factors involved in various cellular functions. However, the function of ZEB2 in OA has not been clearly illustrated.

Method: Interleukin-1β (IL-1β) was used to establish an OA model in vitro. We quantified the ZEB2 expression in cartilage tissues from OA patients and IL-1β-induced chondrocytes through reverse transcription-quantitative polymerase chain reaction and Western blot. We then used functional assays to explore the function of ZEB2 during OA progression.

Results: ZEB2 expression was increased in OA cartilage tissues and chondrocytes. The silencing of ZEB2 increased aggrecan and collagen II levels, and reduced the content of matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13. ZEB2 knockdown inhibited the effects of IL-1β on the production of nitric oxide and prostaglandin E₂, and the expression of inducible nitric oxide synthase and cyclooxygenase-2. ZEB2 inhibition also suppressed the levels of IL-6 and tumour necrosis factor-α, and increased the IL-10 level in IL-1β-treated cells. Mechanically, ZEB2 knockdown blocked the activation of the Wnt/β-catenin pathway in chondrocytes.

Conclusion: Knockdown of ZEB2 alleviated IL-1β-induced cartilage degradation and the inflammatory response through the Wnt/β-catenin pathway in chondrocytes.