StemRegenin 1 attenuates the RANKL-induced osteoclastogenesis via inhibiting AhR- c-src-NF-κB/p-ERK MAPK-NFATc1 signaling pathway

Shengji Zhou; Jiarui Li; Tiantian Ying; Yuxin Wang; Quan Wang; Xiang Li; Fengchao Zhao

doi:10.1016/j.isci.2024.109682

StemRegenin 1 attenuates the RANKL-induced osteoclastogenesis via inhibiting AhR- c-src-NF-κB/p-ERK MAPK-NFATc1 signaling pathway

iScience. 2024 Apr 6;27(5):109682. doi: 10.1016/j.isci.2024.109682. eCollection 2024 May 17.

Authors

Shengji Zhou¹, Jiarui Li¹, Tiantian Ying¹, Yuxin Wang¹, Quan Wang¹, Xiang Li¹, Fengchao Zhao¹

Affiliation

¹ Department of Orthopaedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, P.R. China.

Abstract

The aryl hydrocarbon receptor (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/mitogen-activated protein kinase 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.

Keywords: Cell biology; Immunology; Molecular biology.