University Denis Diderot, 75475 Paris Cedex 10, France.
Bone. 2010 Mar;46(3):571-6. doi: 10.1016/j.bone.2009.07.082. Epub 2009 Aug 4.
Recent progress has been made in our understanding of the functional role of the seven-transmembrane-spanning extracellular calcium-sensing receptor (CaSR) in bone cells. Both in vitro and in vivo data indicate that the CaSR is a physiological regulator of bone cell metabolism. The CaSR regulates the recruitment, differentiation and survival of osteoblasts and osteoclasts through activation of multiple CaSR-mediated intracellular signaling pathways in bone cells. This raises the possibility that the bone CaSR could potentially be targeted by allosteric modulators, either agonists (calcimimetics) or antagonists (calcilytics) to control bone remodeling. The therapeutic potential of CaSR agonists or antagonists in bone cells is however hampered by their effects on the CaSR in nonskeletal tissues. Rather, direct targeting of the bone CaSR may be of potential interest for the treatment of bone diseases. Targeting the bone CaSR using a bone-seeking CaSR agonist offers a potential mean to modulate bone cell metabolism. The development of drugs that preferentially target the CaSR and possibly other cation-sensing receptors in bone cells may thus be helpful for the treatment of osteoporosis.
近年来，我们对跨膜七次的细胞外钙敏感受体（CaSR）在骨细胞中的功能作用有了更多的了解。无论是在体外还是体内数据都表明，CaSR 是骨细胞代谢的生理调节剂。CaSR 通过激活骨细胞中多个 CaSR 介导的细胞内信号通路，调节成骨细胞和破骨细胞的募集、分化和存活。这就提出了一种可能性，即通过变构调节剂（激动剂[钙敏感受体激动剂]或拮抗剂[钙敏感受体拮抗剂]）靶向骨 CaSR，以控制骨重塑。然而，CaSR 激动剂或拮抗剂在骨细胞中的治疗潜力受到其对非骨骼组织中 CaSR 影响的限制。相反，直接靶向骨 CaSR 可能对治疗骨疾病具有潜在意义。使用骨靶向 CaSR 激动剂靶向骨 CaSR 提供了一种调节骨细胞代谢的潜在方法。因此，开发优先靶向骨细胞中的 CaSR 以及可能的其他阳离子敏感受体的药物可能有助于骨质疏松症的治疗。
