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.

Authors’ contributions

Feng Wang contributed to the study conception and design. Material preparation and data collection were performed by Yongzhi Li and Zhiping Sun. Data analysis was performed and software was run by Wenxiong Li and Zhen Xiao. The manuscript was written and revised by Zhibin Li. All authors commented on previous versions of the manuscript, and read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data and materials used to support the findings of this study are available from the corresponding author upon reasonable request.

Ethical approval

The study was carried out in accordance with the Declaration of Helsinki and approved by the ethics committee of the Affiliated Hospital of Shaanxi University of Chinese Medicine (number SZFYIEC-PJ-2022[90]). Informed consent was obtained from all participants.