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Agrimophol suppresses RANKL-mediated osteoclastogenesis through Blimp1-Bcl6 axis and prevents inflammatory bone loss in mice.
In this study, we found that AGR inhibited RANKL-induced osteoclastogenesis, bone-resorption, F-actin ring formation, and the mRNA expression of osteoclast-associated genes such as CTSK, TRAP, MMP-9, and ATP6v0d2 in vitro. In addition, AGR suppressed RANKL-induced expression of c-Fos and NFATc1. However, AGR treatment did not affect NF-κB activation and MAPKs phosphorylation in RANKL-stimulated BMMs, which implicated that AGR might not influence the initial expression of NFATc1 mediated by NF-κB and MAPKs signaling. Our results further indicated that AGR did not alter phosphorylation levels of GSK3β and the expression o...
Source: International Immunopharmacology - November 13, 2020 Category: Allergy & Immunology Authors: Cao J, Wang S, Wei C, Lin H, Zhang C, Gao Y, Xu Z, Cheng Z, Sun WC, Wang HB Tags: Int Immunopharmacol Source Type: research

Leukotriene D4 induces cellular senescence in osteoblasts.
Abstract Aging is associated with the development of osteoporosis, in which cellular senescence in osteoblasts plays a key role. Leukotriene D4 (LTD4), an important cysteinyl leukotriene (cysLT), is a powerful pro-inflammatory mediator formed from arachidonic acid. However, little information regarding the effects of LTD4 on the pathogenesis of osteoporosis has been reported before. In the present study, we defined the physiological roles of LTD4 in cellular senescence in osteoblasts. Our results indicate that LTD4 treatment decreased the expression of SIRT1 in a dose-dependent manner in MC3T3-E1 osteoblastic cell...
Source: International Immunopharmacology - March 24, 2018 Category: Allergy & Immunology Authors: Wei J, Chen S, Guo W, Feng B, Yang S, Huang C, Chu J Tags: Int Immunopharmacol Source Type: research