Osteoarthritis (OA) is a chronic disease and is difficult to cure. Chondrocytes are highly mechanosensitive. Therefore, mechanical therapies have received attention as a therapeutic direction for OA. The stiffness, as a critical cue of the extracellular matrix (ECM), affects cell growth, development, and death. In this study, we use polydimethylsiloxane (PDMS) to create substrates with varying stiffness for chondrocyte growth, interleukin-1β (IL-1β) treatment to mimic the inflammatory environment, and Tubastatin A (Tub A) to inhibit histone deacetylase 6 (HDAC6). Our results show that stiff substrates can be anti-inflammatory and provide a better matrix environment than soft substrates. Inhibition of HDAC6 improves the inflammatory environment caused by IL-1β and coordinates with inflammation to spread the chondrocyte area and primary cilia elongation. Without IL-1β and Tub A treatments, the length of the primary cilia rather than frequency is stiffness-dependent, and their length on stiff substrates are greater than that on soft substrates. In conclusion, we demonstrate that stiff substrates, inflammation, and inhibition of HDAC6 enhance the mechanosensitivity of primary cilia and mediate substrate stiffness to suppress inflammation and protect the matrix.

中文翻译：

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HDAC6 抑制调节软骨细胞中基质硬度介导的炎症信号传导。

骨关节炎（OA）是一种慢性疾病，很难治愈。软骨细胞对机械力高度敏感。因此，机械疗法作为OA的治疗方向受到关注。硬度作为细胞外基质 (ECM) 的关键信号，影响细胞生长、发育和死亡。在这项研究中，我们使用聚二甲基硅氧烷 (PDMS) 制造不同硬度的基质以促进软骨细胞生长，使用白细胞介素 1β (IL-1β) 治疗来模拟炎症环境，并使用图巴他汀 A (Tub A) 来抑制组蛋白脱乙酰酶 6 (HDAC6) 。我们的结果表明，硬质基材可以抗炎，并提供比软质基材更好的基质环境。抑制 HDAC6 可改善 IL-1β 引起的炎症环境，并与炎症协调作用以扩散软骨细胞区域和初级纤毛伸长。如果没有 IL-1β 和 Tub A 处理，初级纤毛的长度而不是频率取决于硬度，并且它们在硬质基底上的长度大于在软质基底上的长度。总之，我们证明坚硬的基质、炎症和 HDAC6 的抑制增强初级纤毛的机械敏感性并介导基质硬度以抑制炎症和保护基质。