González-Casaus María Luisa
Laboratory Medicine, University Hospital La Paz Madrid, Madrid, Spain.
Adv Lab Med. 2023 Dec 12;5(1):24-34. doi: 10.1515/almed-2023-0160. eCollection 2024 Mar.
Bone is more than a reservoir of calcium and phosphorus. Its lacuno-canalicular arrangement provides an important pathway for exchange with circulation and currently, the skeleton is considered a large endocrine organ with actions that go beyond the control of calcium-phosphorus balance mediated by fibroblastic growth factor 23 (FGF23). Parallel to the modulating effect of adipokines on bone turnover, certain bone proteins, such as osteocalcin and sclerostin, play a counter-regulatory role on energy metabolism, probably in an attempt to ensure its high energy requirement for bone turnover. In this crosstalk between bone and other tissues, especially with adipose tissue, canonical Wnt/β-catenin signaling is involved and therefore, sclerostin, an osteocyte derived protein that inhibits this signalling, emerges as a potential biomarker. Furthermore, its involvement in diverse pathologic conditions supports sclerostin as a therapeutic target, with an anti-sclerostin antibody recently approved in our country for the treatment of osteoporosis. This review addresses the endocrine nature of bone, the role of osteocalcin, and specially, the regulatory and modulatory role of sclerostin on bone turnover and energy homeostasis through its inhibitory effect on canonical Wnt/β-catenin signaling, as well as its potential utility as a biomarker.
骨骼不仅仅是钙和磷的储存库。其骨陷窝-骨小管排列为与循环系统进行物质交换提供了重要途径，目前，骨骼被认为是一个大型内分泌器官，其作用超出了成纤维细胞生长因子23（FGF23）介导的钙磷平衡控制范围。与脂肪因子对骨转换的调节作用类似，某些骨蛋白，如骨钙素和硬化素，对能量代谢起反调节作用，这可能是为了满足骨骼转换对高能量的需求。在骨骼与其他组织，尤其是与脂肪组织的这种相互作用中，经典的Wnt/β-连环蛋白信号通路参与其中，因此，作为一种抑制该信号通路的骨细胞衍生蛋白，硬化素成为一种潜在的生物标志物。此外，它在多种病理状况中的作用支持其作为治疗靶点，我国最近已批准一种抗硬化素抗体用于治疗骨质疏松症。本综述阐述了骨骼的内分泌特性、骨钙素的作用，特别是硬化素通过对经典Wnt/β-连环蛋白信号通路的抑制作用对骨转换和能量稳态的调节作用，以及其作为生物标志物的潜在用途。
