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Abstract <p>Osteoarthritis (OA) is a common degenerative bone and joint disease with an unclear pathogenesis. Our study identified that the histone acetyltransferase encoded by <i>Kat7</i> 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 <i>Kat7</i> 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 <i>Kat7</i> was shown to protect chondrocyte function. Corresponding in vivo results indicated that silencing <i>Kat7</i> 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 <i>Kat7</i> overexpression. Collectively, these findings confirm the critical role of KAT7 in the pathogenesis of OA and suggest that <i>Kat7</i> represents a potential therapeutic target for OA treatment.</p> Key messages <p><UnorderedList Mark="Bullet"> <ItemContent> <p>There is a lack of clinically effective drugs for the treatment of osteoarthritis (OA).</p> </ItemContent> <ItemContent> <p><i>Kat7</i> plays a key role in the development of OA.</p> </ItemContent> <ItemContent> <p>Knocking down <i>Kat7</i> expression can alleviate the progression of OA.</p> </ItemContent> <ItemContent> <p><i>Kat7</i> accelerates the progression of OA by activating the TLR4/NF-KB signaling pathway.</p> </ItemContent> </UnorderedList></p>

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Kat7 accelerates osteoarthritis disease progression through the TLR4/NF-κB signaling pathway

  • 期刊论文

  • 发表日期：

    2025年1月28日

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  • Zhen Liu,
  • Lijie Qiu,
  • Yongqiang Zhang,
  • Gang Zhao,
  • Xuecheng Sun,
  • Wenming Luo

摘要

Abstract

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.