2. Academic Validation
  3. Hecogenin alleviates LPS-induced osteolysis via regulating pyroptosis and ROS involved Nrf2 activation

Hecogenin alleviates LPS-induced osteolysis via regulating pyroptosis and ROS involved Nrf2 activation

  • Biomed Pharmacother. 2024 Aug:177:116933. doi: 10.1016/j.biopha.2024.116933.
Zhijuan Liu 1,  Yijie Gao 1,  Xiaoliang Feng 1,  Yuangang Su 1,  Haoyu Lian 1,  Jinmin Zhao 1,  Jiake Xu 2,  Qian Liu 3,  Fangming Song 4
Affiliations

Affiliations

  • 1 Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory of Regenerative Medicine, Orthopaedics Trauma and Hand Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  • 2 Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, China; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; School of Biomedical Sciences, the University of Western Australia, Perth, Australia. Electronic address: jiake.xu@uwa.edu.au.
  • 3 Guangxi Key Laboratory of Regenerative Medicine, Orthopaedics Trauma and Hand Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. Electronic address: liuqian@gxmu.edu.cn.
  • 4 Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory of Regenerative Medicine, Orthopaedics Trauma and Hand Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. Electronic address: songfangming@gxmu.edu.cn.
PMID: 38901204 DOI: 10.1016/j.biopha.2024.116933
Abstract

Reactive oxidative species (ROS) generation triggers Pyroptosis and induces development of inflammatory osteolysis. Hecogenin (HG) has anti-inflammatory and antioxidative property, but its effects on inflammatory osteolysis remains unclear. In our study, we investigated the mechanism of HG on Pyroptosis and its effect on inflammatory osteolysis in vitro and in vivo. The impact of HG on osteoclastogenesis was evaluated using cytotoxicity, TRAcP staining and bone resorption assays. The RNA-sequencing was employed to identify potential signaling pathways, and then RT-qPCR, western blot, immunofluorescence, and ELISA were used to verify. To determine the protective effect of HG in vivo, Lipopolysaccharide (LPS)-induced animal models were utilized, along with micro-CT and histological examination. HG suppressed RANKL-induced osteoclast differentiation, bone resorption, NFATc1 activity and downstream factors. RNA-sequencing results showed that HG inhibited osteoclastogenesis by modulating the inflammatory response and macrophage polarization. Furthermore, HG inhibited the NF-κB pathway, and deactivated the NLRP3 inflammasome. HG activated the expression of nuclear factor E2-related factor 2 (Nrf2) to eliminate ROS generation. Importantly, the inhibitory effect of HG on NLRP3 inflammasome could be reversed by treatment with the Nrf2 inhibitor ML385. In vivo, HG prevented the mice against LPS-induced osteolysis by suppressing osteoclastogenesis and inflammatory factors. In conclusion, HG could activate Nrf2 to eliminate ROS generation, inactivate NLRP3 inflammasome and inhibit Pyroptosis, thereby suppressing osteoclastogenesis in vitro and alleviating inflammatory osteolysis in vivo, which indicating that HG might be a promising candidate to treat inflammatory osteolysis.

Keywords

Hecogenin; NLRP3 inflammasome; Nrf2; Osteoclast; Osteolysis; ROS.

Figures
Products