Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Central Arkansas Veterans Healthcare System, John L. McClellan Little Rock, Little Rock, AR, USA.
Nat Rev Endocrinol. 2024 Nov;20(11):661-672. doi: 10.1038/s41574-024-01014-7. Epub 2024 Jul 17.
Basic, translational and clinical research over the past few decades has provided new understanding on the mechanisms by which activation of the receptor of parathyroid hormone (parathyroid hormone 1 receptor (PTH1R)) regulates bone physiology and pathophysiology. A fundamental change in the field emerged upon the recognition that osteocytes, which are permanent residents of bone and the most abundant cells in bone, are targets of the actions of natural and synthetic ligands of PTH1R (parathyroid hormone and abaloparatide, respectively), and that these cells drive essential actions related to bone remodelling. Among the numerous genes regulated by PTH1R in osteocytes, SOST (which encodes sclerostin, the WNT signalling antagonist and inhibitor of bone formation) has a critical role in bone homeostasis and changes in its expression are associated with several bone pathologies. The bone fragility syndrome induced by diabetes mellitus is accompanied by increased osteocyte apoptosis and changes in the expression of osteocytic genes, including SOST. This Review will discuss advances in our knowledge of the role of osteocytes in PTH1R signalling and the new opportunities to restore bone health in diabetes mellitus by targeting the osteocytic PTH1R-sclerostin axis.
在过去几十年中，基础、转化和临床研究为我们提供了关于甲状旁腺激素受体（甲状旁腺激素 1 受体（PTH1R））激活调节骨生理学和病理生理学机制的新认识。该领域出现了根本性的变化，人们认识到成骨细胞是骨的常驻细胞，也是骨中最丰富的细胞，是 PTH1R（甲状旁腺激素和abaloparatide，分别为）天然和合成配体作用的靶点，这些细胞驱动与骨重塑相关的基本作用。在成骨细胞中受 PTH1R 调节的众多基因中，SOST（编码骨硬化蛋白，WNT 信号拮抗剂和骨形成抑制剂）在骨稳态中具有关键作用，其表达的变化与几种骨病理学有关。糖尿病引起的骨脆性综合征伴随着成骨细胞凋亡的增加和骨细胞基因表达的变化，包括 SOST。本综述将讨论我们对成骨细胞在 PTH1R 信号中的作用的认识进展，以及通过靶向成骨细胞 PTH1R-骨硬化蛋白轴恢复糖尿病患者骨健康的新机会。
