Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions

Abstract

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors—in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins—not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of osteoclastogenesis, osteogenic differentiation of stem cells, and osteoblasts/osteoclasts balance. After introducing the main types of bone cells, their differentiation and cooperation during bone remodeling and fracture healing processes are discussed. Then, the TGF-β superfamily, its signaling via canonical and non-canonical pathways, as well as its regulation by Wnt/Notch or microRNAs are described and discussed. Its important role in bone homeostasis, repair, or disease is also highlighted. Finally, the clinical therapeutic uses of members of the TGF-β superfamily and their associated complications are debated.