TGF-β Family Signaling in Skeletal Development, Maintenance, and Disease

THE TRANSFORMING GROWTH FACTOR-β (TGF-β) FAMILY is critically involved in the development and maintenance of skeletal tissues. In searches for factors with potent cartilage and bone inductive activities, TGF-β was isolated as cartilage-inducing factor (Seyedin et al. 1987), whereas bone morphogenetic proteins (BMPs) were isolated as factors able to induce cartilage and bone formation (Urist 1965; Luyten et al. 1989). The TGF-β family shows extensive redundancy of ligands, receptors, agonists, and antagonists, yet the diverse temporal and spatial patterns of expression of each pathway component allow these signaling factors to direct skeletal development and homeostasis by regulating patterning, cell-fate determination, cell differentiaton, and bone remodeling. The critical roles of each factor are evident in mice with mutations in components of these pathways, whereas in vitro