Jørgensen N R, Syberg S, Ellegaard M
Head of Division, Clinical Biochemistry, Department of Diagnostics, Glostrup Hospital, Ndr. Ringvej 57, DK-2600 Glostrup, Denmark.
Curr Med Chem. 2015;22(7):902-14. doi: 10.2174/0929867321666141215094749.
Bone is a highly dynamic organ, being constantly modeled and remodeled in order to adapt to the changing need throughout life. Bone turnover involves the coordinated actions of bone formation and bone degradation. Over the past decade great effort has been put into the examination of how P2X receptors regulate bone metabolism and especially for the P2X7 receptor an impressive amount of evidence has now documented its expression in osteoblasts, osteoclasts, and osteocytes as well as important functional roles in proliferation, differentiation, and function of the cells of bone. Key evidence has come from studies on murine knockout models and from pharmacologic studies on cells and animals. More recently, the role of P2X receptors in human bone diseases has been documented. Loss-of-functions polymorphisms in the P2X7 receptorare associated with bone loss and increased fracture risk. Very recently a report from a genetic study in multiple myeloma demonstrated that decreased P2X7 receptor function was associated with increased risk of developing multiple myeloma. In contrast, the risk of developing myeloma bone disease and subsequent vertebral fractures was increased in subjects carrying P2X7 receptor gain-of-function alleles as compared to subjects only carrying loss-of-function or normal functioning alleles. It is evident that P2X receptors are important in regulating bone turnover and maintaining bone mass, and thereby holding great potential as novel drug targets for treatment of bone diseases. However, further research is needed before we fully understand the roles and effects of P2X receptors in bone.
骨骼是一个高度动态的器官，为了适应一生中不断变化的需求，它会持续进行塑形和重塑。骨转换涉及骨形成和骨降解的协同作用。在过去十年中，人们付出了巨大努力来研究P2X受体如何调节骨代谢，特别是对于P2X7受体，现在已有大量证据证明其在成骨细胞、破骨细胞和骨细胞中的表达，以及在骨细胞增殖、分化和功能方面的重要作用。关键证据来自对小鼠基因敲除模型的研究以及对细胞和动物的药理学研究。最近，P2X受体在人类骨疾病中的作用也有了相关记录。P2X7受体的功能丧失多态性与骨质流失和骨折风险增加有关。最近一项针对多发性骨髓瘤的基因研究报告表明，P2X7受体功能降低与患多发性骨髓瘤的风险增加有关。相比之下，与仅携带功能丧失或正常功能等位基因的受试者相比，携带P2X7受体功能获得等位基因的受试者发生骨髓瘤骨病和随后椎体骨折的风险增加。显然，P2X受体在调节骨转换和维持骨量方面很重要，因此作为治疗骨疾病的新型药物靶点具有巨大潜力。然而，在我们充分了解P2X受体在骨骼中的作用和影响之前，还需要进一步研究。
