Distinct mechanosensitive Ca2+ influx mechanisms in human primary synovial fibroblasts

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.