Wang Xin-Yue, Niu Zhi-Xing, Zhang De-Mao, Xie Jing, Zhou Xue-Dong
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2022 May;53(3):517-522. doi: 10.12182/20220560304.
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.
骨重塑由成骨细胞的骨生成和破骨细胞的破骨细胞生成精心编排,在生理条件下维持骨发育和代谢的稳态。骨形态发生蛋白1A型受体,也称为激活素受体样激酶3(ALK3),存在于细胞膜上,是骨形态发生蛋白(BMP)因子的关键受体之一,是调节BMP信号进入细胞以执行生物学功能的重要“门户”。BMP信号在骨重塑中的作用已得到广泛研究。近年来,通过基于转基因小鼠模型并以ALK3为靶点的研究报道了许多新发现,为骨重塑、软骨和关节发育以及骨相关疾病的发生和治疗的调控提供了新的线索。已有的认识得到了扩展,但BMPs现有临床应用也出现了新的挑战。因此,我们综述了最近关于ALK3参与骨形成和骨吸收的研究,分析了其在骨调节中的作用机制,总结了ALK3在软骨和颞下颌关节发育中的作用,并报道了临床前研究治疗的最新进展,旨在为后续研究和未来临床应用提供参考。