Suppression of NFATc1 through NF-kB/PI3K signaling pathway by Oleandrin to inhibit osteoclastogenesis and bone resorption

Autor: Zhikun Li, Kai Chen, Qifeng Yu, Yifan Li, Shichao Tong, Ruijun Xu, Ruixi Hu, Yi Zhang, Wei Xu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Engineered Regeneration, Vol 5, Iss 3, Pp 342-349 (2024)
Druh dokumentu: article
ISSN: 2666-1381
DOI: 10.1016/j.engreg.2024.01.005
Popis: Inflammation can initiate osteolysis, which is the breakdown of bone by fully developed osteoclasts. The compound Oleandrin is recognized for its effects against inflammation and tumors. Our objective was to examine the effects of Oleandrin on osteoclastogenesis and osteolysis, both in vitro and in vivo. In vitro, the impact of Oleandrin on osteoclastogenesis was assessed using CCK-8 assays, TRAP staining, and bone resorption assays. Additionally, a mouse model of osteolysis caused by LPS injection into the calvaria was used to conduct an in vivo investigation, examining bone histomorphology, histology, and immunohistochemistry. In vitro, concentrations of 5 nM and 10 nM of Oleandrin were found to be non-cytotoxic based on the results obtained. In vitro, Oleandrin hindered the osteoclastogenesis and bone resorption induced by RANKL. Oleandrin successfully inhibited the phosphorylation of NF-κB p65 and PI3K p85 in osteolytic tissue, thereby suppressing LPS-induced inflammatory osteolysis in mice calvaria during the in vivo study. Furthermore, the Oleandrin-treated group exhibited a noteworthy decrease in the expression level of NFATc1, which is a crucial controller of osteoclastogenesis. To sum up, our discoveries indicate that Oleandrin could hinder osteoclastogenesis and bone resorption, thereby having the ability to suppress inflammation-induced osteolysis. The underlying mechanism involves the NF-κB/PI3K pathway and inhibition of NFATc1 activation. Therefore, the findings suggest that Oleandrin holds potential as a therapeutic remedy for osteolytic ailments.
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