Transforming growth factor-β and skeletal homeostasis

Transforming growth factor (TGF)-βs are unique multifunctional growth factors mainly secreted and stored as a latent complex in the extracellular matrix. The biological functions of TGF-β in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Our recent findings, along with data reported by others, have clearly shown that temporal and spatial activation of TGF-β is involved in the recruitment of stem/progenitor cell participation in the bone remodeling process, whereas sustained abnormalities in TGF-β ligand activation, regardless of genetic or environmental origin, will inevitably disrupt the normal physiology and lead to the pathobiology of musculoskeletal disorders. A comprehensive understanding of the mechanisms that underlie the physiological and pathological effects of TGF-β, and full interpretation of how cells integrate these signals into coherent responses in a context-dependent way, can lead to promising therapeutics for TGF-β-involved musculoskeletal diseases.