IGF signaling pathway in bone and cartilage development, homeostasis, and disease

The skeleton plays a fundamental role in the maintenance of organ function and daily activities. The insulin-like growth factor (IGF) family is a group of polypeptide substances with a pronounced role in osteoblast differentiation, bone development, and metabolism. Disturbance of the IGFs and the IGF signaling pathway is inextricably linked with assorted developmental defects, growth irregularities, and jeopardized skeletal structure. Recent findings have illustrated the significance of the action of the IGF signaling pathway via growth factors and receptors and its interactions with dissimilar signaling pathways (Wnt/β-catenin, BMP, TGF-β, and Hh/PTH signaling pathways) in promoting the growth, survival, and differentiation of osteoblasts. IGF signaling also exhibits profound influences on cartilage and bone development and skeletal homeostasis via versatile cell–cell interactions in an autocrine, paracrine, and endocrine manner systemically and locally. Our review summarizes the role and regulatory function as well as a potentially integrated gene network of the IGF signaling pathway with other signaling pathways in bone and cartilage development and skeletal homeostasis, which in turn provides an enlightening insight into visualizing bright molecular targets to be eligible for designing effective drugs to handle bone diseases and maladies, such as osteoporosis, osteoarthritis, and dwarfism.