Periodic mechanical stress enhances rat chondrocyte area expansion and migration through Src-PLCγ1-ERK1/2 signaling

The signal transduction pathways of chondrocyte area expansion and migration under periodic mechanical stress remain a matter of debate. We explore this question by performing cell culture experiments in our self-developed periodic stress field and perfusion culture system. Under periodic mechanical stress, we find that both rat chondrocyte area and migration are significantly amplified. These changes are associated with increases in the phosphorylation of Src, PLCγ1 and ERK1/2. Area expansion, migration and phosphorylation of PLCγ1-Tyr783 and ERK1/2-Thr202/Tyr204 are inhibited (p < 0.05) after pretreatment with Src inhibitor (PP2). We further demonstrate that area expansion, migration and phosphorylation of ERK1/2-Thr202/Tyr204 are significantly inhibited (p < 0.05) after pretreatment with PLCγ1 inhibitor (U73122); the phosphorylation site of Src-Tyr418 is not affected. After pretreatment with an ERK1/2 inhibitor (PD98059), area expansion and migration are inhibited (p < 0.05), while the phosphorylation sites of Src-Tyr418 and PLCγ1-Tyr783 are not affected. These findings suggest that periodic mechanical stress promotes chondrocyte area expansion and migration in part through the Src-PLCγ1-ERK1/2 signaling pathway.