ALK3在骨研究中的新进展

由成骨钙化与破骨吸收精密协调进行的骨改建确保了生理情况下骨骼发育、代谢的稳态平衡。骨形态发生蛋白受体1A（activin receptor-like kinase 3, ALK3）是骨形态发生蛋白（bone morphogenetic protein, BMP）因子作用于细胞膜上的一个关键受体，是BMP信号流入细胞内发挥生物学效应的重要“门户”。BMP信号对骨改建作用已得到广泛研究，而近年来依托转基因小鼠模型，围绕ALK3靶点对骨改建、软骨与关节发育以及相关疾病发生与治疗的研究有了诸多新发现，拓宽了固有认知，也对现有BMP的临床应用提出了新的挑战。为此，本文汇总近年来ALK3对骨形成及骨吸收的研究，分析其在骨调控方面的作用机制，总结了ALK3在软骨及颞下颌关节发育中的重要作用，同时跟进了ALK3在临床前研究的治疗新进展，以期为后续研究和临床应用提供参考。

Latest Research Findings on the Regulation of Bone Homeostasis by ALK3

Bone remodeling, which is well orchestrated by osteogenesis of osteoblasts and osteoclastogenesis of osteoclasts, maintains the homeostasis of osteal development and metabolism under physiological conditions. Bone morphogenetic protein receptor type 1A, also known as activin receptor-like kinase 3 (ALK3), which exists on cytomembrane, is one of the key receptors of BMP factors, and is an important "gateway" that regulates the entrance of BMP signaling into cells in order to perform biological functions. The roles of BMP signaling in bone remodeling have been extensively studied. Many new discoveries have been reported in recent years through research based on transgenic mice models and focused on ALK3 as targets, shedding new light on the regulations of bone remodeling, cartilage and joint development, and the occurrence and treatment of bone-related diseases. Established understanding has been expanded, but new challenges on existing clinical application of BMPs also appeared. Hence, we reviewed recent studies on ALK3’s involvement in bone formation and bone resorption, analyzed its mechanism of action in bone regulation, summarized the roles of ALK3 in the development of cartilage and temporomandibular joint, and reported the latest progress in treatment in preclinical studies, intending to provide references for subsequent studies and clinical applications in the future.