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.
Highlights
Bone tissue plays several essential physiological roles within the human body, in particular mechanical functions such as protection, rigid support, and an anchoring site for soft organs and metabolic functions [1,2]
The mechanisms based on Wnt and mitogen-activated protein kinase (MAPK) (Mitogen-activated protein kinase) pathways that control reciprocal expression of Runx2 and PPARγ and their phosphorylation state are essential in mesenchymal stem cells (MSCs) fate determination [32]
When mature osteoblasts are surrounded by secreted extracellular matrix, they undergo some morphologic changes characterized by a decreased volume, number of organelles, and star-shaped cell, to become osteocytes
Summary
Bone tissue plays several essential physiological roles within the human body, in particular mechanical functions such as protection, rigid support, and an anchoring site for soft organs (skeletal muscles) and metabolic functions [1,2]. The growth factors belonging to the TGF-β (transforming growth factor β) superfamily ( bone morphogenetic proteins (BMP) and TGF-β1) are known to act locally on bone formation, by stimulating the proliferation and chondrogenic/osteogenic differentiation of mesenchymal stem cells (MSCs) [12]. They constitute promising local therapeutic agents to promote bone repair. The TGF-β superfamily is an evolutionary conserved family of structurally related dimeric factors They are secreted growth factors, which act as multifunctional regulatory peptides involved in a wide range of processes, including cell development, proliferation, and differentiation; wound healing; and carcinogenesis [15,16]. The controversial clinical uses of members of the TGF-β superfamily in orthopedic surgery is debated
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