摘要
骨是高度动态的器官,被不断地建模和改造,以适应整个生命改变的需要。骨反过来协调参与骨的形成和骨的降解。在过去的十年,我们努力研究了P2X受体如何调节骨代谢,特别是 P2X7受体,大量证据数量现在已经证明其表达于成骨细胞,破骨细胞,骨以及在增殖的骨细胞分化中发挥重要的功能。关键的证据来自对基因敲除小鼠的模型研究和对细胞、动物的药理学研究。最近, 人体骨骼疾病中P2X受体的作用已经被报道。P2X7 受体基因多态性功能缺失与骨量丢失和骨折风险的增加相关 。最近一个多发性骨髓瘤的基因研究报告表明,削弱P2X7受体的功能与多发性骨髓瘤的发病率增加有关。与此相反,携带P2X 7受体功能获得性的等位基因的受试者相比只携带功能缺失主体或正常功能的等位基因的受试者显影骨髓瘤骨病和随后的椎体骨折的风险增加。显而易见的是, P2X受体对调节骨代谢和维持骨量很重要,从而成为用于骨疾病治疗的具有很大的潜力新型药物靶标。
关键词: 骨生物学,骨形成,骨吸收,骨转换, P2X受体,成骨细胞,破骨细胞,骨细胞,骨质疏松症,单核苷酸多态性。
Current Medicinal Chemistry
Title:The Role of P2X Receptors in Bone Biology
Volume: 22 Issue: 7
Author(s): N.R. Jorgensen, S. Syberg and M. Ellegaard
Affiliation:
关键词: 骨生物学,骨形成,骨吸收,骨转换, P2X受体,成骨细胞,破骨细胞,骨细胞,骨质疏松症,单核苷酸多态性。
摘要: 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.
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Cite this article as:
N.R. Jorgensen, S. Syberg and M. Ellegaard , The Role of P2X Receptors in Bone Biology, Current Medicinal Chemistry 2015; 22 (7) . https://dx.doi.org/10.2174/0929867321666141215094749
DOI https://dx.doi.org/10.2174/0929867321666141215094749 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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