Matrix stiffness regulates osteoclast fate through integrin-dependent mechanotransduction

. In particular, increased matrix stiffness inhibited the integrin β3-responsive RhoA-ROCK2-YAP-related mechanotransduction and promoted osteoclastogenesis. Notably, preosteoclast development is facilitated by medium-stiffness hydrogel (M-gel) possessing the same stiffness as vessel ranging from 17.5 kPa to 44.6 kPa by partial suppression of mechanotransduction, which subsequently encouraged revascularization and bone regeneration in mice with bone defects. Our works provide an innovative approach for finely regulating osteoclast differentiation by selecting the optimum matrix stiffness and enable us further to develop a matrix stiffness-based strategy for bone tissue engineering.