期刊
JOURNAL OF BIOMEDICAL SCIENCE
卷 12, 期 6, 页码 1013-1020出版社
BMC
DOI: 10.1007/s11373-005-9029-7
关键词
NF-kappa B; nuclear factor kappa B; OCs - osteoclasts
The P2X(7) 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 P2X(7) antagonists on human primary osteoclasts. We found that the level of expression of P2X(7) 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 P2X(7) 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.
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