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    Osteoarthritis (OA) is an aging-related degenerative joint disease with a poorly defined mechanism. Here we report that kindlin-2 is highly expressed in articular chondrocytes and downregulated in the degenerated cartilage of aged mice and patients with OA. Kindlin-2 deletion in articular chondrocytes leads to spontaneous OA and exacerbates instability-induced OA lesions in adult mice. Kindlin-2 deficiency promotes mitochondrial oxidative stress and activates Stat3, leading to Runx2-mediated chondrocyte catabolism. Pharmacological inhibition of Stat3 activation or genetic ablation of Stat3 in chondrocytes reverses aberrant accumulation of Runx2 and extracellular-matrix-degrading enzymes and limits OA deteriorations caused by kindlin-2 deficiency. Deleting Runx2 in chondrocytes reverses structural changes and OA lesions caused by kindlin-2 deletion without downregulating p-Stat3. Intra-articular injection of AAV5-kindlin-2 decelerates progression of aging- and instability-induced knee joint OA in mice. Collectively, we identify a pathway consisting of kindlin-2, Stat3 and Runx2 in articular chondrocytes that is responsible for maintaining articular cartilage integrity and define a potential therapeutic target for OA. © 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.


    Xiaohao Wu, Yumei Lai, Sheng Chen, Chunlei Zhou, Chu Tao, Xuekun Fu, Jun Li, Wei Tong, Hongtao Tian, Zengwu Shao, Chuanju Liu, Di Chen, Xiaochun Bai, Huiling Cao, Guozhi Xiao. Kindlin-2 preserves integrity of the articular cartilage to protect against osteoarthritis. Nature aging. 2022 Apr;2(4):332-347

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    PMID: 37117739

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