StemRegenin 1 attenuates the RANKL-induced osteoclastogenesis and ovariectomized osteoporosis via inhibiting AhR-c-src-NF-κB/p-ERK MAPK-NFATc1 signaling pathway
iScience(2024)
摘要
The AhR pathway may play an important role in the regulation of osteoclasts, but there are still conflicting studies on this aspect, and the specific mechanism of action has not been fully elucidated. Therefore, we conducted this study to find a drug to treat osteoporosis that targets AhR. We found that StemRegenin 1 inhibited RANKL-induced osteoclastogenesis in a concentration-dependent and time-dependent manner. Through further experiments, we found that SR1 can inhibit nuclear transcription of AhR and inhibit c-src phosphorylation, and ultimately regulates the activation of the NF-κB and p-ERK/MAPK pathways. Therefore, for the first time, we discovered the way in which the AhR-c-src-NF-κB/p-ERK MAPK-NFATc1 signaling pathway regulates the expression of osteoclast differentiation-associated proteins. Finally, SR1 was shown to successfully reverse bone loss in OVX mice. These studies provide us with ideas for finding new way to treat osteoporosis.
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关键词
osteoporosis,StemRegenin 1,osteoclast,Aryl hydrocarbon receptor,nuclear factor-kappa B,p-ERK mitogen-activated protein kinase
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