文献类型：期刊文献

英文题名：Interleukin-1 Receptor-Associated Kinase 3 Attenuates Chondrocyte Senescence and Osteoarthritis via Inhibition of the TLR7/9-NF-κB Axis

作者：Tao, Tao[1,2];Yin, Guangrong[2];Wang, Liangliang[2];Wang, Yuji[1,2,3,4]

第一作者：Tao, Tao

通信作者：Wang, YJ[1];Wang, YJ[2];Wang, YJ[3];Wang, YJ[4]

机构：[1]Dalian Med Univ, Grad Sch, Dalian 116044, Peoples R China;[2]Nanjing Med Univ, Changzhou Peoples Hosp 2, Changzhou Med Ctr, Dept Orthoped,Affiliated Hosp 3, Changzhou, Jiangsu, Peoples R China;[3]Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, 222 Silong Rd, Baiyin 730900, Peoples R China;[4]Mayo Clin, Dept Orthoped Surg & Biochem & Mol Biol, Rochester, MN 55905 USA

第一机构：Dalian Med Univ, Grad Sch, Dalian 116044, Peoples R China

通信机构：[1]corresponding author), Dalian Med Univ, Grad Sch, Dalian 116044, Peoples R China;[2]corresponding author), Nanjing Med Univ, Changzhou Peoples Hosp 2, Changzhou Med Ctr, Dept Orthoped,Affiliated Hosp 3, Changzhou, Jiangsu, Peoples R China;[3]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, 222 Silong Rd, Baiyin 730900, Peoples R China;[4]corresponding author), Mayo Clin, Dept Orthoped Surg & Biochem & Mol Biol, Rochester, MN 55905 USA.|[10735]甘肃中医药大学;

年份：2026

卷号：57

期号：3

外文期刊名：JOURNAL OF MOLECULAR HISTOLOGY

收录：;Scopus(收录号：2-s2.0-105036438462);WOS:【SCI-EXPANDED(收录号:WOS:001748735800002)】；

基金：This research received support from the Changzhou International Scientific and Technological Cooperation Program (CZ20230019) awarded to Tao Tao.

语种：英文

外文关键词：IRAK3; Osteoarthritis; Chondrocyte senescence; TLR/NF-kappa B signaling; Inflammation

摘要：Osteoarthritis (OA) is a common degenerative joint disorder associated with aging, marked by chondrocyte senescence, cartilage degradation, and chronic inflammation. Although cellular senescence significantly contributes to OA progression, the molecular mechanisms governing this process are not fully understood. Interleukin-1 receptor-associated kinase 3 (IRAK3) acts as a negative regulator of Toll-like receptor (TLR) signaling; however, its role in OA and chondrocyte senescence remains unclear. We employed bioinformatics analysis, human OA cartilage samples, a destabilization of the medial meniscus (DMM) mouse model, and in vitro assays in ATDC5 chondrocytes to explore the expression and functional role of IRAK3 in OA. To evaluate senescence, mitochondrial function, reactive oxygen species (ROS), and inflammatory signaling, we conducted gain- and loss-of-function experiments alongside biochemical and histological analyses. IRAK3 expression was markedly reduced in both human and murine osteoarthritis (OA) cartilage. Silencing IRAK3 intensified hydrogen peroxide-induced senescence, mitochondrial dysfunction, reactive oxygen species (ROS) production, and catabolic metabolism, whereas its overexpression offered protective effects. Mechanistically, IRAK3 inhibited the TLR7/TLR9-NF-kappa B pathway, leading to decreased secretion of pro-inflammatory cytokines and reduced chondrocyte senescence. In vivo, intra-articular injection of adeno-associated virus (AAV) to knock down IRAK3 can promote the progression of OA in DMM mice. IRAK3 serves as a crucial inhibitor of chondrocyte senescence and the progression of osteoarthritis (OA) by reducing TLR-mediated inflammation and oxidative stress. These findings highlight IRAK3 as a promising therapeutic target for addressing senescence-related osteoarthritis.