Bone marrow mesenchymal stem cells and TGF-β signaling in bone remodeling

During bone resorption, abundant factors previously buried in the bone matrix are released into the bone marrow microenvironment, which results in recruitment and differentiation of bone marrow mesenchymal stem cells (MSCs) for subsequent bone formation, temporally and spatially coupling bone remodeling. Parathyroid hormone (PTH) orchestrates the signaling of many pathways that direct MSC fate. The spatiotemporal release and activation of matrix TGF-beta during osteoclast bone resorption recruits MSCs to bone-resorptive sites. Dysregulation of TGF-beta alters MSC fate, uncoupling bone remodeling and causing skeletal disorders. Modulation of TGF-beta or PTH signaling may reestablish coupled bone remodeling and be a potential therapy.