The LIM-only protein FHL2 controls mesenchymal cell osteogenic differentiation and bone formation through Wnt5a and Wnt10b

► FHL2, a LIM-only protein with four and a half LIM domains, controls mesenchymal cell osteogenic differentiation. ► Here, we report that Wnt3a increases FHL2 expression, and that FHL2 silencing reduces Wnt5a and Wnt10b expression in mesenchymal cells. ► Wnt10b overcomes the negative effect of FHL2 silencing on osteoblast gene expression. ► Wnt5a and Wnt10b expression is reduced in FHL2 knockout mice, which is associated with decreased osteoblast function and bone mass. ► We conclude that FHL2 regulates mesenchymal cell osteogenic differentiation in part through modulation of Wnt molecules.