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肠道-骨骼轴的调节:LC86通过抗炎代谢途径改善骨质疏松和软骨损伤斑马鱼模型的骨骼健康。

Modulation of the gut-bone axis: LC86 improves bone health via anti-inflammatory metabolic pathways in zebrafish models of osteoporosis and cartilage damage.

作者信息

Dong Yao, Sun Yukun, Zhou Zhipeng, Gai Zhonghui, Cai Yihui, Han Mei, Zou Kang

机构信息

Germline Stem Cells and Microenvironment Lab, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.

Stem Cell Research and Translation Center, Nanjing Agricultural University, Nanjing, China.

出版信息

Front Immunol. 2025 Apr 16;16:1493560. doi: 10.3389/fimmu.2025.1493560. eCollection 2025.

DOI:10.3389/fimmu.2025.1493560
PMID:40308595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12041650/
Abstract

AIM

Osteoporosis and cartilage injury are major health concerns with limited treatment options. This study investigates the therapeutic effects of LC86 (LC86) on osteoporosis and cartilage damage in a zebrafish () model, focusing on its modulation of the gut-bone axis and its potential mechanisms for enhancing bone health.

METHODS

A Dexamethasone-induced zebrafish model was used to mimic osteoporosis and cartilage injury. Zebrafish were divided into control, model, and LC86 treatment groups (3×10 CFU/mL). Bone and cartilage health were assessed using Alizarin red staining and fluorescence microscopy. Bone marker expression (, , , , and ) was quantified via qPCR. Metabolic alterations were analyzed using untargeted metabolomics, and changes in gut microbiota were examined through 16S rRNA gene sequencing.

RESULTS

LC86 treatment significantly improved bone and cartilage health, as evidenced by increased fluorescence intensity in the skull, hard bone, and cartilage ( < 0.01, < 0.05). qPCR results showed upregulation of key bone-related genes (, , , , and ), indicating enhanced bone and cartilage structure. Metabolomics analysis revealed alterations in over 300 metabolites, with changes in anti-inflammatory and energy pathways. Gut microbiota analysis demonstrated an increase in beneficial bacteria and a decrease in pathogenic genera.

CONCLUSIONS

LC86 significantly improved bone health, cartilage structure, and gut microbiota composition in a Dexamethasone-induced zebrafish model, supporting its potential as a therapeutic strategy for osteoporosis and cartilage injury via modulation of the gut-bone axis.

摘要

目的

骨质疏松症和软骨损伤是主要的健康问题,治疗选择有限。本研究在斑马鱼模型中研究了LC86对骨质疏松症和软骨损伤的治疗效果,重点关注其对肠-骨轴的调节作用及其促进骨骼健康的潜在机制。

方法

使用地塞米松诱导的斑马鱼模型模拟骨质疏松症和软骨损伤。将斑马鱼分为对照组、模型组和LC86治疗组(3×10 CFU/mL)。使用茜素红染色和荧光显微镜评估骨骼和软骨健康状况。通过qPCR对骨标志物表达(、、、和)进行定量分析。使用非靶向代谢组学分析代谢变化,并通过16S rRNA基因测序检查肠道微生物群的变化。

结果

LC86治疗显著改善了骨骼和软骨健康,颅骨、硬骨和软骨中的荧光强度增加证明了这一点(<0.01,<0.05)。qPCR结果显示关键骨相关基因(、、、和)上调,表明骨骼和软骨结构得到增强。代谢组学分析揭示了300多种代谢物的变化,抗炎和能量途径发生了改变。肠道微生物群分析表明有益细菌增加,致病属减少。

结论

在由地塞米松诱导的斑马鱼模型中,LC86显著改善了骨骼健康、软骨结构和肠道微生物群组成,支持其作为通过调节肠-骨轴治疗骨质疏松症和软骨损伤的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/a0506a8501dc/fimmu-16-1493560-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/17823bbaf427/fimmu-16-1493560-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/544b01d79477/fimmu-16-1493560-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/b07c994c693e/fimmu-16-1493560-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/e3e0a0414f1d/fimmu-16-1493560-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/6fe49275c4e6/fimmu-16-1493560-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/a0506a8501dc/fimmu-16-1493560-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/17823bbaf427/fimmu-16-1493560-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/544b01d79477/fimmu-16-1493560-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/b07c994c693e/fimmu-16-1493560-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/e3e0a0414f1d/fimmu-16-1493560-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/6fe49275c4e6/fimmu-16-1493560-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f948/12041650/a0506a8501dc/fimmu-16-1493560-g006.jpg

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