Deficiency of Macf1 inhibits bone formation by attenuating Bmp2/Smad/Runx2 signalling in osteoblasts. Macf1f/fOsx-Cre mice showed decreased bone mass, deteriorated bone microarchitecture and impaired bone strength. We demonstrated that Macf1 affected differentiation of primary osteoblasts through Bmp2/Smad/Runx2 signalling pathway.