Indian hedgehog (Ihh), a member of the vertebrate hedgehog morphogen family, is 
a key signaling molecule that controls chondrocyte proliferation and 
differentiation. In this study, we show a novel function of Ihh. Namely, it acts 
as an essential mediator of mechanotransduction in cartilage. Cyclic mechanical 
stress greatly induces the expression of Ihh by chondrocytes. This induction is 
abolished by gadolinium, an inhibitor of stretch-activated channels. This 
suggests that the IHH gene is mechanoresponsive. The mechano-induction of Ihh is 
essential for stimulating chondrocyte proliferation by mechanical loading. The 
presence of an Ihh functional blocking antibody during loading completely 
abolishes the stimulatory effect of mechanical load on proliferation. 
Furthermore, Ihh mediates the mechanotransduction process in a bone morphogenic 
protein (BMP)-dependent and parathyroid hormone-related peptide-independent 
manner. BMP 2/4 are up-regulated by mechanical stress through the induction of 
Ihh, and BMP antagonist noggin inhibits mechanical stimulation of chondrocyte 
proliferation. This suggests BMP lies downstream of Ihh in mechanotransduction 
pathway. Our data suggest that Ihh may transduce mechanical signals during 
cartilage growth and repair processes.