Lin Chen, Liesheng Lu, Chunyi Fan, Xiaonan Zhu, Ling Pan, Shanshan Tang, Yufan Wang, Yongde Peng, Li You
{"title":"Autophagy-induced osteoblast-derived exosomes maintain bone formation and prevent osteoporosis by remodeling gut microbiota-metabolism.","authors":"Lin Chen, Liesheng Lu, Chunyi Fan, Xiaonan Zhu, Ling Pan, Shanshan Tang, Yufan Wang, Yongde Peng, Li You","doi":"10.1016/j.bj.2025.100870","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis is a chronic disease of bone metabolism with high incidence rates. Recently, exosome therapy has emerged as a promising avenue for the treatment of osteoporosis. However, the role of autophagy-induced osteoblast-derived exosomes (Auto-exo) in osteoporosis has yet to be elucidated.</p><p><strong>Methods: </strong>The effect of Auto-exo in bone formation was assessed in vivo. The composition of gut microbiota was determined through 16S rDNA sequencing, and metabolite profiles were analyzed using liquid chromatography-mass spectrometry (LC-MS). Cell experiments were conducted to explore the role of bilirubin in bone formation.</p><p><strong>Results: </strong>Auto-exo were successfully isolated and identified. Auto-exo promoted bone formation and alleviated osteoporosis progression in a mouse model of osteoporosis. 16S rDNA sequencing revealed that Auto-exo changed diversity and composition of gut microbiota in osteoporotic mice, with a notable increase in Lactobacillus and a decrease in Dubosiella and Faecalibaculum. LC-MS analysis indicated that Auto-exo treatment reduced the elevated levels of bilirubin in osteoporotic mice. Cell experiments uncovered that bilirubin remarkably inhibited osteoblast differentiation. Furthermore, Auto-exo promoted osteoblast differentiation via inhibiting bilirubin production.</p><p><strong>Conclusions: </strong>Our findings demonstrated that Auto-exo promoted bone formation by modulating the gut microbiota-metabolites bilirubin axis, thereby alleviating osteoporosis progression. This discovery provides a novel perspective on the mechanisms underlying the therapeutic effects of Auto-exo in osteoporosis.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100870"},"PeriodicalIF":4.1000,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.bj.2025.100870","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Osteoporosis is a chronic disease of bone metabolism with high incidence rates. Recently, exosome therapy has emerged as a promising avenue for the treatment of osteoporosis. However, the role of autophagy-induced osteoblast-derived exosomes (Auto-exo) in osteoporosis has yet to be elucidated.
Methods: The effect of Auto-exo in bone formation was assessed in vivo. The composition of gut microbiota was determined through 16S rDNA sequencing, and metabolite profiles were analyzed using liquid chromatography-mass spectrometry (LC-MS). Cell experiments were conducted to explore the role of bilirubin in bone formation.
Results: Auto-exo were successfully isolated and identified. Auto-exo promoted bone formation and alleviated osteoporosis progression in a mouse model of osteoporosis. 16S rDNA sequencing revealed that Auto-exo changed diversity and composition of gut microbiota in osteoporotic mice, with a notable increase in Lactobacillus and a decrease in Dubosiella and Faecalibaculum. LC-MS analysis indicated that Auto-exo treatment reduced the elevated levels of bilirubin in osteoporotic mice. Cell experiments uncovered that bilirubin remarkably inhibited osteoblast differentiation. Furthermore, Auto-exo promoted osteoblast differentiation via inhibiting bilirubin production.
Conclusions: Our findings demonstrated that Auto-exo promoted bone formation by modulating the gut microbiota-metabolites bilirubin axis, thereby alleviating osteoporosis progression. This discovery provides a novel perspective on the mechanisms underlying the therapeutic effects of Auto-exo in osteoporosis.
期刊介绍：
Biomedical Journal publishes 6 peer-reviewed issues per year in all fields of clinical and biomedical sciences for an internationally diverse authorship. Unlike most open access journals, which are free to readers but not authors, Biomedical Journal does not charge for subscription, submission, processing or publication of manuscripts, nor for color reproduction of photographs.
Clinical studies, accounts of clinical trials, biomarker studies, and characterization of human pathogens are within the scope of the journal, as well as basic studies in model species such as Escherichia coli, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealing the function of molecules, cells, and tissues relevant for human health. However, articles on other species can be published if they contribute to our understanding of basic mechanisms of biology.
A highly-cited international editorial board assures timely publication of manuscripts. Reviews on recent progress in biomedical sciences are commissioned by the editors.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
