Mechanical force induces G2/M cell cycle arrest in human osteosarcoma cells and inhibits their differentiation

[[abstract]]Fluid shear stress plays important roles in proliferation and differentiation of bone cells. We investigated the effects of shear stress on MG63 human osteosarcoma cells. Application of shear stress (12 dynes/cm2) to MG63 cells induced G2/M arrest and inhibited differentiation. Pre-treatment of MG63 cells with antibodies against alphavbeta3 and beta1 integrins inhibited these shear-induced responses. Shear stress caused sustained increases in cyclin B and p21CIP1 and decrease in CDK1 expression in MG63 cells. Moreover, shear stress induced sustained activations of Smad1/5 and decrease in runt-related transcription factor 2 (Runx2) activity in MG63 cells. Transfection of MG63 cells with Smad1/5-specifc siRNA inhibited these shear-mediated expression and activation of cell cycle regulators and Runx2. Our results demonstrated that shear stress induces G2/M arrest in MG63 cells and inhibits their differentiation, and that these responses are regulated by alphavbeta3 and beta1 integrins through Smad1/5 and their modulation in Runx2, as well as specific cell cycle regulators. Our findings provide insights into the mechanisms by which shear stress regulates cell cycle progression and differentiation in human osteosarcoma cells