ANXA2 Improves Inflammatory Injury in ATDC5 Cells by Regulating YAP and p38 MAPK Signaling Pathways

doi:10.13701/j.cnki.kqyxyj.2025.03.012

Abstract

Abstract: Objective: To investigate the role and molecular mechanism of Annexin A2 (ANXA2) in inflammatory injury of ATDC5 cells induced by IL-1β. Methods: After injecting the temporomandibular joint of mice with monosodium iodoacetate (MIA) or saline for 2 weeks,the condylar sections were analyzed the expression level of ANXA2 in arthritis cartilage. qRT-PCR was used to detect the effects of different concentrations of IL-1β on ANXA2 and cartilage anabolism markers SRY-box transcription factor 9 (Sox9) and collagen type Ⅱ alphal chain (Col2a1), cartilage catabolism markers matrix metalloproteinase 13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin 5 (Adamts5), and inflammatory response-related factors cyclooxygenase 2 (Cox2) and inducible nitric oxide synthase (iNOS) in ATDC5 cells. After ATDC5 cells were transfected with lentiviruses that knocked down and overexpressed ANXA2, transfection efficiency was detected by Western blotting. qRT-PCR and Western blot were used to detect the effects of ANXA2 on the mRNA and protein expressions of cartilage catabolism, anabolism, and inflammation-related factors in ATDC5 cells under physiological and inflammatory conditions, respectively. Western blot was used to detect the phosphorylation levels of Yes-associated protein (YAP) and p38 mitogen-activated protein kinase (p38 MAPK), as well as the protein expression levels of SOX9, MMP-13, and iNOS after the addition of the YAP inhibitor Verteporfin. Results: The condylar cartilage of MIA-induced temporomandibular joint osteoarthritis mice significantly degenerated, and the expression of ANXA2 in arthritic cartilage increased.As the concentration of IL-1β increased, the expression of cartilage anabolism markers decreased, while the expression of cartilage catabolism and inflammatory response markers and ANXA2 increased significantly.Knockdown of ANXA2 inhibited cartilage anabolism under inflammatory conditions and promoted cartilage catabolism and the expression of inflammatory-related factors; overexpression of ANXA2 showed the opposite results.Overexpression of ANXA2 promoted YAP phosphorylation under inflammatory conditions and inhibited p38 phosphorylation. Inhibition of YAP could partially reverse the protective effect of ANXA2 on inflammatory injury in ATDC5 cells. Conclusion: ANXA2 improves IL-1β-induced inflammatory injury of ATDC5 cells partially by regulating YAP and p38 MAPK pathways.

Key words: chondrocytes, inflammatory injury, YAP signaling pathway, p38 MAPK signaling pathway

WANG Xinru, WANG Xinyi, YANG Chang, DONG Wei, WANG Jiawei. ANXA2 Improves Inflammatory Injury in ATDC5 Cells by Regulating YAP and p38 MAPK Signaling Pathways[J]. Journal of Oral Science Research, 2025, 41(3): 243-249.

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