Effects of the fat mass and obesity-associated gene on apoptosis and the inflammatory response of chondrocytes in osteoarthritis
10.3760/cma.j.issn.0254-9026.2024.02.013
- VernacularTitle:脂肪量和肥胖相关基因对骨关节炎软骨细胞凋亡和炎症反应的影响
- Author:
Lini DONG
1
;
Haoyu HE
;
Lei KUANG
;
Zejun CHEN
;
Xiaoxiao WANG
;
Bing WANG
;
Guohua LYU
Author Information
1. 中南大学湘雅二医院老年科，长沙 410011
- Keywords:
Osteoarthritis;
Chondrocytes;
Inflammation;
Apoptosis
- From:
Chinese Journal of Geriatrics
2024;43(2):221-227
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects of the fat mass and obesity-associated gene(FTO)on apoptosis and the inflammatory response of chondrocytes in osteoarthritis(OA).Methods:Differences in FTO expression between normal human cartilage tissue samples and OA cartilage tissue samples were examined.Primary OA chondrocytes were isolated and cultured, and a rat OA model was constructed.The expression of FTO was detected in clinical, animal and cellular samples.Cells were treated with an FTO knockdown lentivirus vector(sh-FTO)and an m 6A methylation inhibitor(cycloleucine). The amount of m 6A and the expression levels of inflammatory cytokines, interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α), were detected.Flow cytometry was used to detect apoptosis in OA chondrocytes, and Western blot was used to detect the expression levels of B-cell lymphoma 2(Bcl-2)and Bcl-2-associated X protein(Bax). Results:Compared with the normal control group, FTO mRNA and protein expression in human OA cartilage tissue, rat OA cartilage tissue and OA chondrocytes was significantly increased(all P<0.05). After FTO knockdown, the level of m 6A increased, the levels of IL-6 and TNF-α decreased considerably, the apoptosis rate decreased, the expression of the proapoptotic protein Bax decreased considerably, and the expression of Bcl-2 increased considerably in primary OA chondrocytes.However, cycloleucine intervention clearly reduced the level of m6A, increased the levels of IL-6 and TNF-α, promoted cell apoptosis and the expression of apoptosis-related proteins, and reversed the effect induced by the FTO knockdown lentivirus in OA chondrocytes(all P<0.05). Conclusions:FTO may be involved in mechanisms related to the action of m 6A to promote OA chondrocyte apoptosis and the inflammatory response, thus accelerating the progression of OA.
