广西医科大学学报2025，Vol.42Issue(2)：174-184,11.DOI:10.16190/j.cnki.45-1211/r.2025.02.003
基于RANKL/RANK/TRAF6信号通路和肠道菌群探讨买麻藤醇对骨质疏松性骨缺损小鼠的影响
Effect of gnetol on osteoporotic bone defect mice based on RANKL/RANK/TRAF6 and gut microbiota
摘要
Abstract
Objective:To explore the potential mechanism of gnetol in the treatment of osteoporotic bone defects and its effect on the gut microbiota.Methods:A total of 30 C57BL/6J mice were randomly divided into sham group,model group,alendronate sodium group,low-dose gnetol group,and high-dose gnetol group.An osteopo-rosis model was constructed by bilateral ovarian enucleation,and then a skull defect model was constructed using lipopolysaccharide(LPS)on this model.Micro-CT and hematoxylin-eosin(HE)staining were used to observe the bone mineral density and bone microstructure of the skull of mice,the expression of tumor necrosis factor-α(TNF-α)and C-terminal telopeptide of type Ⅰ collagen(CTX-I)in the serum was detected by enzyme-linked im-munosorbent assay(ELISA),the expression of cathepsin K(CTSK)was detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and the expression of NFATc1,c-fos,TNF-α,TRAP,CTSK,RANK,TRAF6,RANKL,p-p65 and p-IκBα was detected by western blotting.The abundance of gut microbiota in the sham,model and high-dose groups was detected by 16sRNA sequencing.Results:Compared with the sham group,the BMD and bone microstructure of the skull in the model group were significantly damaged.The protein expression levels of TRAP,CTSK,CTX-I,TNF-α,c-Fos,NFATc1,as well as those related to the osteo-clast differentiation pathway(RANK,RANKL,TRAF6),inflammatory pathway(p-P65 and p-IκBα)were in-creased,and the expression of bone resorption marker CTSK gene was also increased.Moreover,the gut micro-biota richness was increased,while the structure of the normal gut microbiota community was disrupted.Gnetol ameliorated impaired bone microarchitecture and bone loss caused by lipopolysaccharide(LPS)in osteoporotic states,inhibited the protein expression of TNF-α,c-Fos and NFATc1 which promote osteoclast differentiation,as well as the protein expression of the osteoclast differentiation pathways(RANK,RANKL,TRAF6)and inflam-matory pathways(p-P65,p-IκBα),and reduced the gene expression of CTSK.It reduced the abundance of harm-ful bacteria such as Lachnospiraceae and Alistipes that have a negative impact on bone tissue,and increased the abundance of beneficial bacteria such as Erysipelothrichaceae,and Bifidobacteriaceae(including Bifidobacte-rium).Conclusion:Gnetol effectively ameliorates bone microstructural disruption and excessive bone resorption in the body due to LPS in osteoporotic states.It down-regulates the expression of the RANKL/RANK/TRAF6 sig-naling pathway,inhibits the activation of the NF-κB signaling pathway,and regulates the abundance of both ben-eficial and harmful bacteria.关键词
买麻藤醇/破骨细胞/骨质疏松性骨缺损/RANK/RANKL/TRAF6信号通路/肠道菌群Key words
gnetol/osteoclast/osteoporotic bone defects/RANK/RANKL/TRAF6 signaling pathway/gut micro-biota分类
临床医学引用本文复制引用
韦宇杭,曾高峰..基于RANKL/RANK/TRAF6信号通路和肠道菌群探讨买麻藤醇对骨质疏松性骨缺损小鼠的影响[J].广西医科大学学报,2025,42(2):174-184,11.基金项目
国家自然科学基金(No.82260437) （No.82260437）
广西科技基地和人才专项资助项目(No.桂科AD23026324) （No.桂科AD23026324）
