- 作者: Letizia Penolazzi; Ercolina Bianchini; Elisabetta Lambertini; Pier Giovanni Baraldi; Romeo Romagnoli; Roberta Piva; Roberto Gambari
- 作者服務機構: 1 Department of Biochemistry and Molecular Biology, Molecular Biology section, University of Ferrara, 44100, Ferrara, Italy; ; 2 Department of Pharmaceutical Sciences, University of Ferrara, 44100, Ferrara, Italy; ; 3 Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, 44100, Ferrara, Italy; ; 4 ER-GenTech, University of Ferrara, 44100, Ferrara, Italy
- 中文摘要: --
- 英文摘要: The P2X7 nucleotide receptor is an ATP-gated ion channel that plays an important role in bone cell function. Here, we investigated the effects of l-tyrosine derivatives 1-3 as potent P2X7 antagonists on human primary osteoclasts. We found that the level of expression of P2X7 receptor increased after treatment with the derivatives 1-3, together with the induction of high levels of apoptosis. This effect is associated with activation of caspase-3 and inhibition of expression of IL-6. Interestingly, no pro-apoptotic effect of compounds 1-3 was found on human osteoblasts. Our results suggest that the development of specific P2X7 receptor antagonists may be considered a useful tool to modulate apoptosis of human osteoclasts. Since bone loss due to osteoclast-mediated resorption represents one of the major unsolved problem in osteopenic disorders, the identification of molecules able to induce apoptosis of osteoclasts is of great interest for the development of novel therapeutic strategies.
- 中文關鍵字: --
- 英文關鍵字: apoptosis, osteoclasts, P2X7 receptor