Liu Zhen, Qiu Lijie, Zhang Yongqiang, Zhao Gang, Sun Xuecheng, Luo Wenming
Department of Orthopedics, The First Affiliated Hospital of Weifang Medical University (Weifang People's Hospital), Weifang, 261000, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Weifang Medical University (Weifang People's Hospital), Weifang, 261000, China.
J Mol Med (Berl). 2025 Mar;103(3):273-284. doi: 10.1007/s00109-025-02519-y. Epub 2025 Jan 28.
Osteoarthritis (OA) is a common degenerative bone and joint disease with an unclear pathogenesis. Our study identified that the histone acetyltransferase encoded by Kat7 is upregulated in the affected articular cartilage of OA patients and in a mice model of medial meniscal instability-induced OA. Chondrocyte-specific knockdown of Kat7 expression exhibited a protective effect on articular cartilage integrity. In vitro experiments demonstrated that KAT7 promotes cartilage catabolism, inhibits cartilage anabolism, and induces chondrocyte senescence and apoptosis. Conversely, knocking down Kat7 was shown to protect chondrocyte function. Corresponding in vivo results indicated that silencing Kat7 effectively enhances cartilage anabolism, prevents articular cartilage damage, and significantly slows OA progression. Mechanistically, KAT7 activates the TLR4/NF-κB signaling pathway, and inhibition of this pathway reverses the catabolic effects and restores anabolic activity in the presence of Kat7 overexpression. Collectively, these findings confirm the critical role of KAT7 in the pathogenesis of OA and suggest that Kat7 represents a potential therapeutic target for OA treatment. KEY MESSAGES: There is a lack of clinically effective drugs for the treatment of osteoarthritis (OA). Kat7 plays a key role in the development of OA. Knocking down Kat7 expression can alleviate the progression of OA. Kat7 accelerates the progression of OA by activating the TLR4/NF-KB signaling pathway.
骨关节炎（OA）是一种常见的退行性骨和关节疾病，其发病机制尚不清楚。我们的研究发现，Kat7编码的组蛋白乙酰转移酶在OA患者受影响的关节软骨以及内侧半月板不稳定诱导的OA小鼠模型中上调。软骨细胞特异性敲低Kat7表达对关节软骨完整性具有保护作用。体外实验表明，KAT7促进软骨分解代谢，抑制软骨合成代谢，并诱导软骨细胞衰老和凋亡。相反，敲低Kat7可保护软骨细胞功能。相应的体内结果表明，沉默Kat7可有效增强软骨合成代谢，预防关节软骨损伤，并显著减缓OA进展。机制上，KAT7激活TLR4/NF-κB信号通路，抑制该通路可逆转分解代谢作用，并在Kat7过表达的情况下恢复合成代谢活性。总的来说，这些发现证实了KAT7在OA发病机制中的关键作用，并表明Kat7是OA治疗的潜在治疗靶点。关键信息：目前缺乏治疗骨关节炎（OA）的临床有效药物。Kat7在OA的发展中起关键作用。敲低Kat7表达可缓解OA的进展。Kat7通过激活TLR4/NF-KB信号通路加速OA的进展。
