HUMAN OSTEOBLAST-LIKE CELLS RESPOND TO MECHANICAL STRAIN WITH INCREASED BONE-MATRIX PROTEIN-PRODUCTION INDEPENDENT OF HORMONAL-REGULATION

Exposure of osteosarcoma cell lines to chronic intermittent strain inc reases the activity of mechano-sensitive cation (SA-cat) channels. The impact of mechano-transduction on osteoblast function has not been we ll studied. We analyzed the expression and production of bone matrix p roteins in human osteoblast-like osteosarcoma cells, OHS-4, in respons e to chronic intermittent mechanical strain. The OHS-4 cells exhibit t ype I collagen production, 1,25-Dihydroxyvitamin D-inducible osteocalc in, and mineralization of the extracellular matrix. The matrix protein message level was determined from total RNA isolated from cells expos ed to 1-4 days of chronic intermittent strain. Northern analysis for t ype I collagen indicated that strain increased collagen message after 48 h. Immunofluorescent labeling of type I collagen demonstrated that secretion was also enhanced with mechanical strain. Osteopontin messag e levels were increased severalfold by the application of mechanical l oad in the absence of vitamin D, and the two stimuli together produced an additive effect. Osteocalcin secretion was also increased with cyc lic strain. Osteocalcin levels were not detectable in vitamin D-untrea ted control cells. However, after 4 days of induced load, significant levels of osteocalcin were observed in the medium. With vitamin D pres ent, osteocalcin levels were 4 times higher in the medium of strained cells compared to nonstrained controls. We conclude that mechanical st rain of osteoblast-like cells is sufficient to increase the transcript ion and secretion of matrix proteins via mechano-transduction without hormonal induction.