Department of Orthopaedics, Juntendo University School of Medicine, Tokyo, Japan.
J Orthop Res. 2010 Jul;28(7):859-64. doi: 10.1002/jor.21080.
Synovial cells are exposed to continually changing dynamic forces and are implicated in the maintenance of joint homeostasis. However, the mechanisms of synovial cell responses to mechanical stress are unclear. In this study, we investigated the difference between the mechanosensitive channels of human primary synovial fibroblasts (SFBs) and human primary dermal fibroblasts (DFBs) in response to mechanical stretch by uniaxial cyclic stretching and mechanical cell membrane deformation in vitro. Cyclic stretching induced orientation of SFBs and DFBs perpendicularly to the stretching direction. Furthermore, uniaxial stretching increased intracellular Ca(2+) levels in both cell types. The perpendicular orientation of DFBs was blocked by gadolinium (III) chloride (Gd(3+), a mechanosensitive Ca(2+) channel blocker) or ruthenium red (RR, a nonselective Ca(2+) channel blocker). However, Gd(3+) did not block the stretch-induced perpendicular orientation in SFBs, while RR inhibited this orientation. Similarly, Ca(2+) influx in DFBs induced by uniaxial stretching and membrane deformation was inhibited by Gd(3+), RR, and GsMTx-4 (another mechanosensitive Ca(2+) channel blocker), while only RR inhibited Ca(2+) influx in SFBs. Our results suggest that SFBs respond to mechanical stretch through mechanosensitive channels that are distinct from those of DFBs.
滑膜细胞暴露于不断变化的动态力中，并被认为与关节内稳态的维持有关。然而，滑膜细胞对机械应激的反应机制尚不清楚。在这项研究中，我们通过体外的单轴循环拉伸和细胞膜机械变形研究了人原代滑膜成纤维细胞（SFBs）和人原代真皮成纤维细胞（DFBs）对机械拉伸的机械敏感通道的差异。循环拉伸诱导 SFBs 和 DFBs 垂直于拉伸方向排列。此外，单轴拉伸增加了两种细胞类型的细胞内 Ca(2+)水平。DFBs 的垂直排列被钆（III）氯化物（Gd(3+)，一种机械敏感的 Ca(2+)通道阻断剂）或钌红（RR，一种非选择性的 Ca(2+)通道阻断剂）阻断。然而，Gd(3+) 并没有阻断 SFBs 中拉伸诱导的垂直取向，而 RR 抑制了这种取向。同样，Gd(3+)、RR 和 GsMTx-4（另一种机械敏感的 Ca(2+)通道阻断剂）抑制了 DFBs 中单轴拉伸和细胞膜变形诱导的 Ca(2+)内流，而只有 RR 抑制了 SFBs 中的 Ca(2+)内流。我们的结果表明，SFBs 通过不同于 DFBs 的机械敏感通道对机械拉伸作出反应。
