Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1
Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1
复制标题
DOI：
10.1016/j.yexcr.2019.111556
复制
发表时间：
2019-10-15
影响因子：
3.7
通讯作者：
Hirohata, Satoshi
中科院分区：
文献类型：
--
作者：
Ohtsuki, Takashi;Shinaoka, Akira;Hirohata, Satoshi
骨关节炎 (OA) 患者的滑液中炎症细胞因子水平升高，可诱导软骨细胞中解整合素和具有血小板反应蛋白基序的金属蛋白酶 (ADAMTS) 以及基质金属蛋白酶 (MMP) 的表达。机械应变对生物体有不同的影响，具体取决于压力源的强度、周期和持续时间。然而，尚不清楚在炎症刺激下机械应变如何作用。在这里，我们发现机械应变减弱了炎症细胞因子诱导的基质降解酶的表达。循环拉伸应变 (CTS) 作为机械应激源，可减弱正常软骨细胞 (NHAC-kn) 和软骨细胞系 (OUMS-27) 中白细胞介素 (IL)-1 beta 和肿瘤坏死因子 (TNF)-alpha 诱导的 ADAMTS4、ADAMTS9 和 MMP-13 的 mRNA 表达。通过用机械门控通道抑制剂（例如钆、瞬时受体电位（TRP）家族抑制剂、钌红）以及药理和小干扰RNA介导的TRPV1抑制处理细胞，可以消除这种效应。此外，CTS 还消除了细胞因子刺激导致的核因子 kappa B (NF-kappa B) 从细胞质到细胞核的易位。这些发现表明，TRPV 蛋白等机械传感器是治疗 OA 的潜在治疗靶点。
The synovial fluids of patients with osteoarthritis (OA) contain elevated levels of inflammatory cytokines, which induce the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and of the matrix metalloproteinase (MMP) in chondrocytes. Mechanical strain has varying effects on organisms depending on the strength, cycle, and duration of the stressor; however, it is unclear under inflammatory stimulation how mechanical strain act on. Here, we show that mechanical strain attenuates inflammatory cytokine-induced expression of matrix-degrading enzymes. Cyclic tensile strain (CTS), as a mechanical stressor, attenuated interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha-induced mRNA expression of ADAMTS4, ADAMTS9, and MMP-13 in normal chondrocytes (NHAC-kn) and in a chondrocytic cell line (OUMS-27). This effect was abolished by treating cells with mechano-gated channel inhibitors, such as gadolinium, transient receptor potential (TRP) family inhibitor, ruthenium red, and with pharmacological and small interfering RNA-mediated TRPV1 inhibition. Furthermore, nuclear factor kappa B (NF-kappa B) translocation from the cytoplasm to the nucleus resulting from cytokine stimulation was also abolished by CTS. These findings suggest that mechanosensors such as the TRPV protein are potential therapeutic targets in treating OA.