文献类型：期刊文献

英文题名：Theaflavin-3,3′-digallate attenuates chondrocyte senescence via modulating FGF7 and KEAP1/NRF2 signaling pathway

作者：Kou, Hongwei[1];Lu, Feng[2];Li, Maoyuan[2];Liu, Yimin[2];Li, Shishou[1];Yin, Guangrong[3];Chen, Jie[6];Zhao, Gongyin[3];Wang, Liangliang[3];Wang, Yuji[3,4,5];Xu, Chao[6]

第一作者：Kou, Hongwei

通信作者：Wang, YJ[1];Xu, C[2]

机构：[1]Dalian Med Univ, Sch Grad, 9 West Sect,Shunnan Rd, Dalian 116044, Peoples R China;[2]Nanjing Med Univ, Nanjing 210000, Peoples R China;[3]Nanjing Med Univ, Peoples Hosp Changzhou 2, Dept Orthoped, Affiliated Hosp 3, Changzhou 213003, Peoples R China;[4]Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, 222 Silong Rd, Baiyin 730900, Peoples R China;[5]Nanjing Med Univ, Peoples Hosp Changzhou 2, Ctr Bone Dis Rehabil, Affiliated Hosp 3, Changzhou 213003, Peoples R China;[6]Nanjing Med Univ, Peoples Hosp Changzhou 2, Trauma Cent, Affiliated Hosp 3, Changzhou 213003, Peoples R China

第一机构：Dalian Med Univ, Sch Grad, 9 West Sect,Shunnan Rd, Dalian 116044, Peoples R China

通信机构：[1]corresponding author), Nanjing Med Univ, Peoples Hosp Changzhou 2, Dept Orthoped, Affiliated Hosp 3, Changzhou 213003, Peoples R China;[2]corresponding author), Nanjing Med Univ, Peoples Hosp Changzhou 2, Trauma Cent, Affiliated Hosp 3, Changzhou 213003, Peoples R China.

年份：2026

卷号：253

起止页码：1

外文期刊名：FREE RADICAL BIOLOGY AND MEDICINE

收录：;Scopus(收录号：2-s2.0-105039307836);WOS:【SCI-EXPANDED(收录号:WOS:001780616500001)】；

基金：This work was supported by grants from the Changzhou Science Technology Program (grant number CJ20245028), the Changzhou Science and Technology Bureau (grant number WZ202204), Changzhou No. 2. People's Hospital Foundation (grant number YJRC202437), the Clinical Research Project of Changzhou Medical Center of Nanjing Medical University (grant number CZKYCMCB202215). This work was also supported by Changzhou key medical breakthrough technology: one-stop resuscitation and combined surgery for severe polytrauma.

语种：英文

外文关键词：Osteoarthritis; Cellular senescence; Theaflavin-3; 3 ' -digallate; Fibroblast growth factor 7; Nuclear factor erythroid -related factor 2

摘要：Studies have demonstrated that chondrocyte senescence is involved in the pathological progression of osteoarthritis. This study aimed to investigate the effect of TF3 on chondrocyte senescence and its underlying molecular mechanism. Primary chondrocytes were isolated from mice, and senescence-related markers, mitochondrial metabolism levels, and the expression of the FGF7/Keap1-NRF2-related pathway were examined using CCK-8 assay, Western blot, beta-galactosidase staining, and fluorescence staining. RNA sequencing and molecular docking were further employed to explore the mechanisms by which TF3 inhibits chondrocyte senescence. A mouse model of destabilization of the medial meniscus (DMM) was established, and the anti-senescence and cartilage protective effects of TF3 were evaluated through H&E staining, immunohistochemistry, micro-CT, and Safranin O/Fast Green staining. The results showed that TF3 suppressed the expression of senescence-associated proteins, including p16Ink4a, p21, IL-6, and MMP13, while promoting the expression of Coll2a1 in IL-1 beta induced cell senescence model. Additionally, TF3 reduced beta-galactosidase activity and alleviated DNA damage. RNA sequencing and experimental findings revealed that the anti-senescence effect of TF3 might be related to the regulation of oxidative stress and mitochondrial metabolism. Furthermore, the FGF7 and Keap1/NRF2 pathway were involved in TF3-mediated inhibition of chondrocyte senescence. NRF2 knockdown and exogenous rFGF7 supplementation abrogated the protective effects of TF3 against chondrocyte senescence. Animal experiments further confirmed that TF3 exerted anti-senescence effects and delayed joint degeneration. This study reveals important molecular mechanisms by which TF3 inhibits chondrocyte senescence and retards OA progression, suggesting that TF3 may serve as a potential novel therapeutic strategy for OA.