Osteoporosis is a widespread disease characterized by bone mass loss and microarchitectural deterioration. The side effects of clinical drugs make mesenchymal stem cells (MSCs)-based therapy gain increasing focus in the treatment of osteoporosis. MSCs need to migrate to the site of damage and undergo differentiation in order to participate in the subsequent bone repair process. Therefore, the homing ability of MSCs may be related to the repair ability. Here, we proposed a novel method to screen MSCs with high migration capacity and confirmed that these MSCs exhibited higher osteogenic differentiation ability both in vivo and in vitro. Further results indicated that MSCs with high migration ability could partly rescue the bone loss of ovarectomized (OVX) rats. Higher expression of Platelet-derived growth factors receptor β- (PDGFRβ) and more nuclear transduction of β-catenin in MSCs with high migration ability may be responsible for biological functions. This article may provide a method to improve the efficacy of MSCs-based therapy in the clinic. MSCs with high migration ability promote bone remodeling through the PDGFR/Wnt/β-catenin pathway. (A) MSCs with high migration ability rescue bone loss in OVX mice. (B) Potential mechanisms for differences in the multidirectional differentiation ability of MSCs with different migratory abilities. • Increased osteogenic differentiation and reduced lipogenic differentiation of MSCs with high migration capacity. • MSCs with high migration capacity partially rescued bone loss in OVX rats. • More PDGFRβ expression and activation of the Wnt/β-catenin pathway in MSCs with high migratory capacity.