Grebennikova T A, Belaya Zh E, Rozhinskaya L Ya, Melnichenko G A
Endocrinology Research Center, Ministry of Health of Russia, Moscow, Russia.
Ter Arkh. 2016;88(10):74-81. doi: 10.17116/terarkh201688674-81.
The Wnt/β signaling pathway (Wnt-SP) is a phylogenetically ancient mechanism that regulates development and maintains tissue homeostasis through the control of cell proliferation, differentiation, migration, and apoptosis. The accurate regulation of the canonical Wnt/β-catenin signaling pathway (Wnt-SP) is critical for embryogenesis and postnatal development; and impaired signal transduction at one of its stages leads to various diseases, including organ malformations, cancers, metabolic and neurodegenerative disorders. The literature review discusses the biological role of the canonical Wnt-SP in the development of the skeleton and in the remodeling of bone tissue. The Wnt signal transmission changes observed during genetic mutations cause various human skeletal diseases. Understanding the functional mechanism involved in the development of bone abnormality could open new horizons in the treatment of osteoporosis, by affecting the Wnt-SP. The design of antibodies to sclerostin, a Wnt-SP inhibitor, is most promising now. The paper summarizes the studies that have investigated the canonical Wnt-SP and designed drugs to treat osteoporosis.
Wnt/β信号通路（Wnt-SP）是一种在系统发育上古老的机制，通过控制细胞增殖、分化、迁移和凋亡来调节发育并维持组织稳态。经典Wnt/β-连环蛋白信号通路（Wnt-SP）的精确调控对于胚胎发育和出生后发育至关重要；其任何一个阶段的信号转导受损都会导致各种疾病，包括器官畸形、癌症、代谢和神经退行性疾病。文献综述讨论了经典Wnt-SP在骨骼发育和骨组织重塑中的生物学作用。基因突变过程中观察到的Wnt信号传递变化会导致各种人类骨骼疾病。了解骨异常发育所涉及的功能机制可能会通过影响Wnt-SP为骨质疏松症的治疗开辟新的前景。目前，针对Wnt-SP抑制剂硬化蛋白设计抗体最具前景。本文总结了研究经典Wnt-SP并设计治疗骨质疏松症药物的相关研究。
