Molecular regulation of mechanotransduction.

There is a common mechanism for mechanotransduction in cells, regardless of the cell type. Integrins, interacting with their matrix/environment, mediate increases in intracellular Ca2+ levels and activate MAP kinase cascades to cause ERK1/2 phosphorylation. Phosphorylated ERK1/2 causes the activation of the AP-1 family of transcription factors that are necessary for the pro-growth response. The pro-bone growth response involves upregulation of the genes c-fos, IGF-1, cyclooxygenase, and osteocalcin. In osteocytes, increases in intracellular Ca2+ levels may additionally occur by extracellular Ca2+ influx through a stretch-activated ion channel. Each bone cell appears fine-tuned for the type of stimulus, with accessory mechanotransduction signaling pathways, such as calcineurin-mediated activation of the tissue-specific transcription factor NF-AT, adjusting the outcome of signaling in each case.