当前位置: X-MOL 学术Theranostics › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Probiotics Stimulate Bone Formation in Obese Mice via Histone Methylations
Theranostics ( IF 12.4 ) Pub Date : 2021-7-25 , DOI: 10.7150/thno.63749
Jyotirmaya Behera 1 , Jessica Ison 1 , Michael J Voor 2, 3 , Neetu Tyagi 1
Affiliation  

Rationale: Manipulation of the gut microbiome can prevent pathologic bone loss. However, the effects of probiotics on mitochondrial epigenetic remodeling and skeletal homeostasis in the high-fat diet (HFD)-linked obesity remains to be explored. Here, we examined the impact of probiotics supplementation on mitochondrial biogenesis and bone homeostasis through the histone methylation mechanism in HFD fed obese mice./nMethods: 16S rRNA gene sequencing was performed to study the microbiota composition in the gut and microbial dysbiosis in obese mouse model. High resolution (microPET/CT) imaging was performed to demonstrate the obese associated colonic inflammation. Obese-associated upregulation of target miRNA in osteoblast was investigated using a microRNA qPCR array. Osteoblastic mitochondrial mass was evaluated using confocal imaging. Overexpression of mitochondrial transcription factor (Tfam) was used to investigate the glycolysis and mitochondrial bioenergetic metabolism using Tfam-transgenic (Tg) mice fed on HFD. The bone formation and mechanical strength was evaluated by microCT analysis and three-point bending analysis./nResults: High-resolution imaging (µ-CT) and mechanical testing revealed that probiotics induced a significant increase of trabecular bone volume and bone mechanical strength respectively in obese mice. Probiotics or Indole-3-propionic acid (IPA) treatment directly to obese mice, prevents gut inflammation, and improved osteoblast mineralization. Mechanistically, probiotics treatment increases mitochondrial transcription factor A (Tfam) expression in osteoblasts by promoting Kdm6b/Jmjd3 histone demethylase, which inhibits H3K27me3 epigenetic methylation at the Tfam promoter. Furthermore, Tfam-transgenic (Tg) mice, fed with HFD, did not experience obesity-linked reduction of glucose uptake, mitochondrial biogenesis and mineralization in osteoblasts./nConclusions: These results suggest that the probiotics mediated changes in the gut microbiome and its derived metabolite, IPA are potentially be a novel agent for regulating bone anabolism via the gut-bone axis.

中文翻译:

益生菌通过组蛋白甲基化刺激肥胖小鼠的骨形成

理由:对肠道微生物组的操作可以防止病理性骨质流失。然而,益生菌对高脂饮食(HFD)相关肥胖症中线粒体表观遗传重塑和骨骼稳态的影响仍有待探索。在这里,我们通过 HFD 喂养的肥胖小鼠的组蛋白甲基化机制检查了补充益生菌对线粒体生物发生和骨稳态的影响。/n方法:进行 16S rRNA 基因测序以研究肥胖小鼠模型中肠道中的微生物群组成和微生物失调。进行高分辨率 (microPET/CT) 成像以证明肥胖相关的结肠炎症。使用 microRNA qPCR 阵列研究了成骨细胞中与肥胖相关的靶 miRNA 上调。使用共聚焦成像评估成骨细胞线粒体质量。线粒体转录因子 (Tfam) 的过表达用于研究使用以 HFD 喂养的 Tfam 转基因 (Tg) 小鼠的糖酵解和线粒体生物能量代谢。通过显微CT分析和三点弯曲分析评估骨形成和机械强度。/n结果:高分辨率成像 (µ-CT) 和机械测试表明,益生菌分别显着增加了肥胖小鼠的骨小梁体积和骨机械强度。益生菌或吲哚-3-丙酸 (IPA) 直接治疗肥胖小鼠,预防肠道炎症,并改善成骨细胞矿化。从机制上讲,益生菌治疗通过促进 Kdm6b/Jmjd3 组蛋白去甲基化酶来增加成骨细胞中线粒体转录因子 A (Tfam) 的表达,该酶抑制 Tfam 启动子处的 H3K27me3 表观遗传甲基化。此外,喂食 HFD 的 Tfam 转基因 (Tg) 小鼠没有经历与肥胖相关的成骨细胞中葡萄糖摄取、线粒体生物发生和矿化的减少。/n结论:这些结果表明,益生菌介导肠道微生物组及其衍生代谢物 IPA 的变化可能是一种通过肠道-骨轴调节骨合成代谢的新型药物。
更新日期:2021-08-15
down
wechat
bug