Calcium Regulates Cyclic Compression-Induced Early Changes In Chondrocytes During In Vitro Tissue Formation

A single application of cyclic compression to bioengineered cartilage improves tissue formation through cell shape changes that are mediated by α5β1 integrin and membrane-type metalloprotease (MT1-MMP). To determine if this response is controlled by calcium, we investigated how calcium regulated cell shape changes, MT1-MMP and integrin activity in response to stimulation. Stimulation-induced changes in cell shape and MT1-MMP expression were abolished with chelation of extracellular calcium, and reinstated with its re-introduction. Spreading and retraction were inhibited by blocking the stretch-activated and L-Type voltage- gated channels, respectively; channel blocking also inhibited MT1-MMP upregulation. Channels’ role was confirmed through treatment with calcium A23187 ionophore, which alleviated the effects of channel blocking. Calcium regulated the integrin-mediated signalling pathway, which was facilitated through the kinase Src. Both calcium- and integrin-mediated pathways converged on activating ERK in response to stimulation. Understanding the molecular mechanisms regulating chondrocyte mechanotransduction may lead to the development of improved bioengineered cartilage.