College of Life Science and Medicine, Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Zhejiang Sci-Tech University, Hangzhou, China.
Clinical Laboratory, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China.
FASEB J. 2024 Sep 15;38(17):e70031. doi: 10.1096/fj.202401298R.
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.
骨骼在维持器官功能和日常活动中起着至关重要的作用。胰岛素样生长因子 (IGF) 家族是一组具有明显作用的多肽物质，在成骨细胞分化、骨发育和代谢中发挥作用。IGFs 和 IGF 信号通路的紊乱与各种发育缺陷、生长异常和骨骼结构受损密切相关。最近的研究结果表明，通过生长因子和受体，IGF 信号通路的作用及其与不同信号通路（Wnt/β-catenin、BMP、TGF-β 和 Hh/PTH 信号通路）的相互作用在促进成骨细胞的生长、存活和分化方面具有重要意义。IGF 信号通路还通过自分泌、旁分泌和内分泌方式在全身和局部的多种细胞-细胞相互作用中对软骨和骨骼发育以及骨骼内稳态产生深远影响。我们的综述总结了 IGF 信号通路与其他信号通路在骨骼和软骨发育及骨骼内稳态中的作用和调节功能，以及潜在的综合基因网络，这反过来为可视化有希望的分子靶标提供了一个启示，以便有资格设计有效的药物来治疗骨骼疾病和失调，如骨质疏松症、骨关节炎和侏儒症。
