TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease

The transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways are pivotal regulators of cellular processes, playing indispensable roles in embryogenesis, postnatal development, and tissue homeostasis. These pathways are particularly critical within the skeletal system, as they coordinate osteogenesis, chondrogenesis, and bone remodeling through intricate molecular mechanisms. TGF-β/BMP signaling is primarily transduced via canonical Smad-dependent pathways (e.g., ligands, receptors, and intracellular Smads) and the non-canonical Smad-independent (e.g., p38 mitogen-activated protein kinase, MAPK) cascade. Both pathways converge on master transcriptional regulators, including…