Regulation of bone-associated genes in smooth muscle with mechanical strain

Calcification is a common problem associated with cardiovascular disease, injury, aging, and as a result of biomaterial implantation. Osteopontin (OPN) and matrix gla protein (MGP) are key bone-associated molecules in the calcification process, and we hypothesize that mechanical strain is an important signal mediating their expression in the cardiovasculature. To address this, we studied the effects of cyclic mechanical strain (7% strain, 1 Hz) on bone-associated gene expression in rat aortic smooth muscle cells grown in a three-dimensional tissue model. Mechanical strain was found to modulate the expression of OPN, MGP, and CBFA-1, a transcription factor normally found in osteoblasts. Significant increases in their expression were noted without chronic cyclic strain exposure. Long-term strain of these tissues appeared to play a protective role in regards to calcification, as strained tissues exhibited decreased amounts of total calcium. with respect to controls. These studies suggest that mechanical strain is an important signal in maintaining the smooth muscle phenotype, and its absence leads cells to switch to a phenotype that is more bone-like.