ELECTROPHYSIOLOGICAL RESPONSES OF HUMAN BONE-CELLS TO MECHANICAL STIMULATION - EVIDENCE FOR SPECIFIC INTEGRIN FUNCTION IN MECHANOTRANSDUCTION

Bone cells respond to mechanical stimuli, but the transduction mechani sms responsible are not fully understood, Integrins, a family of heter odimeric transmembrane glycoproteins, which link components of the ext racellular matrix with the actin cytoskeleton, have been implicated as mechanoreceptors. We have assessed the roles of integrins in the tran sduction of cyclical mechanical stimuli to human bone cells (HBCs), wh ich results in changes in membrane potential, HBC showed membrane depo larization following 0.104 Hz mechanical stimulation and membrane hype rpolarization following stimulation at 0.33 Hz, The membrane depolariz ation response involved tetrodotoxin-sensitive sodium channels and cou ld be inhibited by antibodies against alpha V, beta 1, and beta 5 inte grins. In contrast, the hyperpolarization response was inhibited by ga dolinium and antibodies to the integrin-associated protein (CD47), alp ha 5 and beta 1 integrin, Both responses could be abrogated by Arg-Gly -Asp (RGD)-containing peptides, inhibition of tyrosine kinase activity , and disruption of the cytoskeleton, These results demonstrate differ ential electrophysiological responses of HBC to different frequencies of mechanical strain, Furthermore, they suggest that integrins act as HBC mechanoreceptors with distinct signaling pathways being activated by different frequencies of mechanical stimuli.