Cianferotti L, Gomes A R, Fabbri S, Tanini A, Brandi M L
Metabolic Bone Diseases Unit, Department of Surgery and Translational Medicine, University of Florence, 50134, Florence, Italy.
Osteoporos Int. 2015 Aug;26(8):2055-71. doi: 10.1007/s00198-015-3203-1. Epub 2015 Jun 23.
The calcium-sensing receptor (CaSR), a key player in the maintenance of calcium homeostasis, can influence bone modeling and remodeling by directly acting on bone cells, as demonstrated by in vivo and in vitro evidence. The modulation of CaSR signaling can play a role in bone anabolism.
The calcium-sensing receptor (CaSR) is a key player in the maintenance of calcium homeostasis through the regulation of PTH secretion and calcium homeostasis, thus indirectly influencing bone metabolism. In addition to this role, in vitro and in vivo evidence points to direct effects of CaSR in bone modeling and remodeling. In addition, the activation of the CaSR is one of the anabolic mechanisms implicated in the action of strontium ranelate, to reduce fracture risk.
This review is based upon the acquisition of data from a PubMed enquiry using the terms "calcium sensing receptor," "CaSR" AND "bone remodeling," "bone modeling," "bone turnover," "osteoblast," "osteoclast," "osteocyte," "chondrocyte," "bone marrow," "calcilytics," "calcimimetics," "strontium," "osteoporosis," "skeletal homeostasis," and "bone metabolism."
A fully functional CaSR is expressed in osteoblasts and osteoclasts, so that these cells are able to sense changes in the extracellular calcium and as a result modulate their behavior. CaSR agonists (calcimimetics) or antagonists (calcilytics) have the potential to indirectly influence skeletal homeostasis through the modulation of PTH secretion by the parathyroid glands. The bone anabolic effect of strontium ranelate, a divalent cation used as a treatment for postmenopausal and male osteoporosis, might be explained, at least in part, by the activation of CaSR in bone cells.
Calcium released in the bone microenvironment during remodeling is a major factor in regulating bone cells. Osteoblast and osteoclast proliferation, differentiation, and apoptosis are influenced by local extracellular calcium concentration. Thus, the calcium-sensing properties of skeletal cells can be exploited in order to modulate bone turnover and can explain the bone anabolic effects of agents developed and employed to revert osteoporosis.
钙敏感受体（CaSR）是维持钙稳态的关键因素，体内和体外证据表明，它可通过直接作用于骨细胞来影响骨塑形和重塑。CaSR信号传导的调节可在骨合成代谢中发挥作用。
钙敏感受体（CaSR）通过调节甲状旁腺激素（PTH）分泌和钙稳态，在维持钙稳态中起关键作用，从而间接影响骨代谢。除此之外，体内和体外证据表明CaSR对骨塑形和重塑有直接作用。此外，CaSR的激活是雷奈酸锶发挥作用以降低骨折风险的合成代谢机制之一。
本综述基于通过在PubMed上检索“钙敏感受体”“CaSR”以及“骨重塑”“骨塑形”“骨转换”“成骨细胞”“破骨细胞”“骨细胞”“软骨细胞”“骨髓”“钙敏感受体拮抗剂”“钙敏感受体激动剂”“锶”“骨质疏松症”“骨骼稳态”和“骨代谢”等术语获取的数据。
成骨细胞和破骨细胞中表达有功能完整的CaSR，因此这些细胞能够感知细胞外钙的变化，并据此调节其行为。CaSR激动剂（钙敏感受体激动剂）或拮抗剂（钙敏感受体拮抗剂）有可能通过调节甲状旁腺分泌PTH间接影响骨骼稳态。雷奈酸锶是一种用于治疗绝经后和男性骨质疏松症的二价阳离子，其骨合成代谢作用至少部分可通过激活骨细胞中的CaSR来解释。
重塑过程中骨微环境中释放的钙是调节骨细胞的主要因素。成骨细胞和破骨细胞的增殖、分化和凋亡受局部细胞外钙浓度影响。因此，可利用骨骼细胞的钙传感特性来调节骨转换，并可解释为逆转骨质疏松症而研发和使用的药物的骨合成代谢作用。
