Sulforaphene suppresses RANKL-induced osteoclastogenesis and LPS-induced bone erosion by activating Nrf2 signaling pathway

Hantao Yao; Yangge Du; Bulin Jiang; Yilin Liao; Yaoyu Zhao; Mengjie Yin; Ting Li; Yue Sheng; Yaoting Ji; Minquan Du

doi:10.1016/j.freeradbiomed.2023.07.009

Sulforaphene suppresses RANKL-induced osteoclastogenesis and LPS-induced bone erosion by activating Nrf2 signaling pathway

Free Radic Biol Med. 2023 Oct:207:48-62. doi: 10.1016/j.freeradbiomed.2023.07.009. Epub 2023 Jul 7.

Authors

Hantao Yao¹, Yangge Du¹, Bulin Jiang¹, Yilin Liao¹, Yaoyu Zhao¹, Mengjie Yin¹, Ting Li¹, Yue Sheng¹, Yaoting Ji², Minquan Du³

Affiliations

¹ The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
² The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: yaotingji@whu.edu.cn.
³ The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: duminquan@whu.edu.cn.

PMID: 37423561
DOI: 10.1016/j.freeradbiomed.2023.07.009

Abstract

Background and purpose: Inflammatory disorders have been found to induce bone loss through sustained and persistent activation of osteoclast differentiation, leading to heightened bone resorption. The current pharmacological interventions for combating bone loss to harbor adverse effects or contraindications. There is a pressing need to identify drugs with fewer side effects.

Experimental approach: The effect and underlying mechanism of sulforaphene (LFS) on osteoclast differentiation were illustrated in vitro and in vivo with RANKL-induced Raw264.7 cell line osteoclastogenesis and lipopolysaccharide (LPS)-induced bone erosion model.

Key results: In this study, LFS has been shown to effectively impede the formation of mature osteoclasts induced from both Raw264.7 cell line and bone marrow macrophages (BMMs), mainly at the early stage. Further mechanistic investigations uncovered that LFS suppressed AKT phosphorylation. SC-79, a potent AKT activator, was found to reverse the inhibitory impact of LFS on osteoclast differentiation. Moreover, transcriptome sequencing analysis revealed that treatment with LFS led to a significant upregulation in the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant-related genes. Then it's validated that LFS could promote NRF2 expression and nuclear translocation, as well as effectively resist oxidative stress. NRF2 knockdown reversed the suppression effect of LFS on osteoclast differentiation. In vivo experiments provide convincing evidence that LFS is protective against LPS-induced inflammatory osteolysis.

Conclusion and implications: These well-grounded and promising findings suggest LFS as a promising agent to addressing oxidative-stress related diseases and bone loss disorders.

Keywords: Bone loss; Nrf2; Osteoclast differentiation; Sulforaphene.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Resorption* / chemically induced
Bone Resorption* / drug therapy
Bone Resorption* / genetics
Cell Differentiation
Humans
Lipopolysaccharides / pharmacology
NF-E2-Related Factor 2 / genetics
NF-E2-Related Factor 2 / metabolism
NF-kappa B / metabolism
Osteoclasts / metabolism
Osteogenesis*
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism
RANK Ligand / genetics
RANK Ligand / pharmacology
Signal Transduction

Substances

Lipopolysaccharides
sulphoraphene
NF-E2-Related Factor 2
Proto-Oncogene Proteins c-akt
RANK Ligand
NF-kappa B