FLUID SHEAR-STRESS INCREASES TRANSFORMING-GROWTH-FACTOR-BETA-1 EXPRESSION IN HUMAN OSTEOBLAST-LIKE CELLS - MODULATION BY CATION CHANNEL BLOCKADES

Mechanical stress is an important regulator of bone metabolism. Fluid shear stress caused by mechanical load in bone tissue has been shown t o be important to both the bone structure and function through its eff ects on osteocytes and osteoblasts. We explored the effects of the flu id shear stress on the expression of growth factors and cytokines in h uman osteoblast-like SaOS-2 cells with a purpose-built cone-plate visc ometer. We showed that the physiological level (1.7-2.0 Pascal) of flu id shear stress increased the mRNA expression of TGF-beta 1 about thre efold after 3 hours and also increased TGF-beta 1 protein about threef old after 24 hours in the SaOS-2 cells. However, no mRNA expression of PDGF-A, IGF-I, IGF-II, or IL-6 was detected. To explore the mechanism of up-regulation of TGF-beta 1 expression, we examined the effects of a stretch activated cation nonselective (SA-cat) channel blockade wit h gadolinium and a voltage-dependent L-type Ca2+ channel blockade with verapamil on the TGF-beta 1 expression at the mRNA levels. The fluid shear stress-induced increase in the TGF-beta 1 mRNA levels was signif icantly inhibited by both gadolinium and verapamil. These findings sug gest that the physiological level of fluid shear stress induces the pr oduction of TGF-beta 1 by the SaOS-2 cells via the cation channel func tion and, as a result, may therefore promote bone formation.