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

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

“…Husain et al (35) confirmed that activation of PLCγ1 is required for vascular endothelial growth factor receptor-2 (VEGFR-2)-induced endothelial cell proliferation in vitro. It has been demonstrated that in our previous study (12) periodic mechanical stress can up-regulate the phosphorylation of PLCγ1 in chondrocytes, leading to cell area expansion and migration. Given the broad spectrum of roles in which PLCγ1 is involved, it is possible that PLCγ1 is associated with other mechanical stress responses of chondrocytes, including proliferation and matrix synthesis.…”

“…Hung et al (10) found that MEK-ERK1/2 participates in fluid flow-induced chondrocyte mechanotransduction, leading to regulation of expression of the aggrecan gene, and Perera et al (13) demonstrated that activated ERK1/2 signaling is required for the mitogenic response of human chondrocytes to cyclic mechanical strain. A previous study by our group has also confirmed that periodic mechanical stress promotes rat chondrocyte area expansion and migra-tion through the ERK1/2 signaling pathway (12). The MEK1/2-ERK1/2 signal is regulated by many kinases (14)(15)(16); however, the upstream mediators of MEK1/2-ERK1/2, which are responsible for periodic mechanical stimulation-induced chondrocyte proliferation and matrix synthesis, have not been completely characterized.…”

“…Construction of a periodic mechanical stress field. A periodic stress field of the perfusion culture system with adjustable stress intensity and frequency was built by connecting the reciprocating intensifier pump to the air-tight cell culture device through a barrier type pressure transducer, as previously described (12). The pressure in this system ranged from 0 to 300 kPa and the frequency from 0 to 1 Hz.…”

“…Indeed, these different signaling transduction pathways initiated by the same stimuli can also converge upon some signaling molecules, such as ERK1/2, mediating different cellular responses (17,18). Our previous study demonstrated that periodic mechanical stress promotes chondrocyte area expansion and migration through the Src-PLCγ1-ERK1/2 signaling pathway (12). Thus, one concern is whether or not cyclic mechanical stimulation modulates chondrocyte proliferation and matrix synthesis through the Src-PLCγ1-MEK1/2-ERK1/2 signaling pathway as well.…”

“…MEK1/2 and ERK1/2 exist in virtually all eukaryotic cells and control fundamental cellular functions (6)(7)(8). There is increasing evidence that MEK and ERK1/2 are involved in the regulation of chondrocyte proliferation, matrix synthesis, and migration in response to periodic mechanical stimulation (9)(10)(11)(12). Hung et al (10) found that MEK-ERK1/2 participates in fluid flow-induced chondrocyte mechanotransduction, leading to regulation of expression of the aggrecan gene, and Perera et al (13) demonstrated that activated ERK1/2 signaling is required for the mitogenic response of human chondrocytes to cyclic mechanical strain.…”