Department of Medicine, McGill University, 687 Pine Avenue West, Montreal, QC H3A 1A1, Canada.
Nat Rev Endocrinol. 2015 May;11(5):298-307. doi: 10.1038/nrendo.2015.30. Epub 2015 Mar 10.
The extracellular calcium-sensing receptor, CaSR, is a member of the G protein-coupled receptor superfamily and has a critical role in modulating Ca(2+) homeostasis via its role in the parathyroid glands and kidneys. New evidence suggests that CaSR expression in cartilage and bone also directly regulates skeletal homeostasis. This Review discusses the role of CaSR in chondrocytes, through which CaSR contributes to the development of the cartilaginous growth plate, as well as in osteoblasts and osteoclasts, through which CaSR has effects on skeletal development and bone turnover in young and mature animals. The interaction of skeletal CaSR activation with parathyroid hormone (PTH), which is secreted by the parathyroid gland, can lead to net bone formation in trabecular bone or net bone resorption in cortical bone. Allosteric modulators of CaSR are beneficial in some clinical conditions, with effects that are mediated by the ability of these agents to alter levels of PTH and improve Ca(2+) homeostasis. However, further insights into the action of CaSR in bone cells might lead to CaSR-based drugs that maximize not only the effects of the receptor on the parathyroid glands and kidneys but also on bone.
细胞外钙敏感受体（CaSR）是 G 蛋白偶联受体超家族的成员，通过其在甲状旁腺和肾脏中的作用，在调节钙稳态方面发挥着关键作用。新的证据表明，软骨和骨骼中的 CaSR 表达也直接调节骨骼稳态。本综述讨论了 CaSR 在软骨细胞中的作用，通过该作用，CaSR 有助于软骨生长板的发育，以及在成骨细胞和破骨细胞中的作用，通过该作用，CaSR 对幼年和成年动物的骨骼发育和骨转换有影响。骨骼 CaSR 激活与甲状旁腺激素（PTH）的相互作用，甲状旁腺分泌 PTH，可导致小梁骨的净骨形成或皮质骨的净骨吸收。CaSR 的变构调节剂在某些临床情况下是有益的，其作用是通过这些药物改变 PTH 水平和改善钙稳态的能力来介导的。然而，进一步了解 CaSR 在骨细胞中的作用可能会导致基于 CaSR 的药物，这些药物不仅能最大限度地发挥受体对甲状旁腺和肾脏的作用，而且还能发挥对骨骼的作用。
