Department of Clinical Biochemistry, Rigshospitalet, Valdemar Hansens Vej 13, DK-2600 Glostrup, Denmark; OPEN, Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, J.B.Winsløws Vej 9, DK-5000 Odense C, Denmark.
Curr Opin Pharmacol. 2019 Aug;47:97-101. doi: 10.1016/j.coph.2019.02.013. Epub 2019 Apr 5.
Osteoclasts are cells of the hematopoietic lineage that are responsible for bone resorption. Their activity is crucial in the initiation of bone remodeling and for maintenance of a strong and healthy skeleton. However, in a number of diseases, including inflammatory disorders, inappropriately high osteoclast activity results in excessive bone degradation, bone loss, and subsequently fractures. A range of P2X purinergic receptors are expressed in bone cells, and osteoclasts express most of the P2X receptors. However, until recently only the role of the P2X7 receptor subtype in normal and pathophysiologic bone metabolism was documented while very few studies addressed the role of the remaining six P2X receptor subtypes. Recently, studies have documented that the P2X5 receptor not only controls osteoclastic bone resorption but also mediates inflammation-induced bone loss, while P2X2/3 receptors have dual functions in bone, both regulating bone resorption and mediating bone pain. Finally, an in vivo study showed that reduced P2X7 receptor function aggravates estrogen-withdrawal-induced bone loss, which is in line with the growing number of reports cementing the association between P2X7 receptor polymorphisms and development of osteoporosis and fracture risk. The studies reviewed in this article provide intriguing results highlighting the potential of P2X receptors as promising pharmaceutical targets in the treatment of bone loss associated with inflammatory (and other) diseases.
破骨细胞是造血谱系中的细胞，负责骨吸收。它们的活性对于骨重塑的启动和维持强壮健康的骨骼至关重要。然而，在许多疾病中，包括炎症性疾病，破骨细胞的异常高活性导致过度的骨降解、骨丢失，随后导致骨折。一系列 P2X 嘌呤能受体在骨细胞中表达，破骨细胞表达大多数 P2X 受体。然而，直到最近，只有 P2X7 受体亚型在正常和病理生理骨代谢中的作用得到了记录，而很少有研究涉及其余六个 P2X 受体亚型的作用。最近的研究表明，P2X5 受体不仅控制破骨细胞的骨吸收，还介导炎症引起的骨丢失，而 P2X2/3 受体在骨中有双重功能，既能调节骨吸收，又能介导骨痛。最后，一项体内研究表明，降低 P2X7 受体功能会加重雌激素缺失引起的骨丢失，这与越来越多的报告一致，这些报告证实了 P2X7 受体多态性与骨质疏松症和骨折风险发展之间的关联。本文综述的研究提供了有趣的结果，强调了 P2X 受体作为治疗与炎症（和其他）疾病相关的骨丢失的有前途的药物靶点的潜力。
