{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:43:39Z","timestamp":1784720619259,"version":"3.55.0"},"reference-count":48,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000840"],"award-info":[{"award-number":["82000840"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Journal"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.bj.2025.100870","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T19:26:26Z","timestamp":1746559586000},"page":"100870","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"title":["Autophagy-induced osteoblast-derived exosomes maintain bone formation and prevent osteoporosis by remodeling gut microbiota-metabolism"],"prefix":"10.1016","volume":"49","author":[{"given":"Lin","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesheng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyi","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongde","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bj.2025.100870_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2020.115286","article-title":"Risk of major osteoporotic fracture after first, second and third fracture in Swedish women aged 50 years and older","volume":"134","author":"S\u00f6reskog","year":"2020","journal-title":"Bone"},{"key":"10.1016\/j.bj.2025.100870_bib2","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/978-981-13-3681-2_16","article-title":"Osteoporosis and the ageing skeleton","volume":"91","author":"Aspray","year":"2019","journal-title":"Subcell Biochem"},{"issue":"8","key":"10.1016\/j.bj.2025.100870_bib3","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2021.21106","article-title":"Prevalence of osteoporosis and fracture in China: The China Osteoporosis Prevalence Study","volume":"4","author":"Wang","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"Suppl 6","key":"10.1016\/j.bj.2025.100870_bib4","doi-asserted-by":"crossref","first-page":"s92","DOI":"10.7861\/clinmedicine.15-6-s92","article-title":"Recent advances in the pathogenesis and treatment of osteoporosis","volume":"15 Suppl 6","author":"Curtis","year":"2015","journal-title":"Clin Med"},{"issue":"3","key":"10.1016\/j.bj.2025.100870_bib5","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1302\/2046-3758.103.BJR-2020-0327.R1","article-title":"Do E-cigarettes and vaping have a lower risk of osteoporosis, nonunion, and infection than tobacco smoking?","volume":"10","author":"Nicholson","year":"2021","journal-title":"Bone Joint Res"},{"issue":"16","key":"10.1016\/j.bj.2025.100870_bib6","doi-asserted-by":"crossref","first-page":"9465","DOI":"10.3390\/ijms23169465","article-title":"Current status of the diagnosis and management of osteoporosis","volume":"23","author":"Aibar-Almazan","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"12","key":"10.1016\/j.bj.2025.100870_bib7","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/s41419-019-2159-z","article-title":"eIF2alpha signaling regulates autophagy of osteoblasts and the development of osteoclasts in OVX mice","volume":"10","author":"Li","year":"2019","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.bj.2025.100870_bib8","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.freeradbiomed.2021.05.014","article-title":"Timosaponin BII improved osteoporosis caused by hyperglycemia through promoting autophagy of osteoblasts via suppressing the mTOR\/NFkappaB signaling pathway","volume":"171","author":"Wang","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.bj.2025.100870_bib9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12986-020-00449-9","article-title":"Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy","volume":"17","author":"Wang","year":"2020","journal-title":"Nutr Metab"},{"issue":"9","key":"10.1016\/j.bj.2025.100870_bib10","doi-asserted-by":"crossref","first-page":"8583","DOI":"10.18632\/aging.103168","article-title":"Gut microbiota and metabolite alterations associated with reduced bone mineral density or bone metabolic indexes in postmenopausal osteoporosis","volume":"12","author":"He","year":"2020","journal-title":"Aging"},{"issue":"4","key":"10.1016\/j.bj.2025.100870_bib11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.cmet.2020.08.012","article-title":"Warmth prevents bone loss through the gut microbiota","volume":"32","author":"Chevalier","year":"2020","journal-title":"Cell Metab"},{"issue":"4","key":"10.1016\/j.bj.2025.100870_bib12","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.jcmgh.2020.10.011","article-title":"Hepatic autophagy deficiency remodels gut microbiota for adaptive protection via FGF15-FGFR4 signaling","volume":"11","author":"Yan","year":"2021","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"12","key":"10.1016\/j.bj.2025.100870_bib13","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1111\/jgh.16381","article-title":"Rapamycin extenuates experimental colitis by modulating the gut microbiota","volume":"38","author":"Guo","year":"2023","journal-title":"J Gastroenterol Hepatol"},{"issue":"45","key":"10.1016\/j.bj.2025.100870_bib14","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abi6442","article-title":"Disruption of autophagy by increased 5-HT alters gut microbiota and enhances susceptibility to experimental colitis and Crohn\u2019s disease","volume":"7","author":"Haq","year":"2021","journal-title":"Sci Adv"},{"issue":"5","key":"10.1016\/j.bj.2025.100870_bib15","doi-asserted-by":"crossref","first-page":"3040","DOI":"10.1021\/acs.nanolett.9b00287","article-title":"Reversal of osteoporotic activity by endothelial cell-secreted bone targeting and biocompatible exosomes","volume":"19","author":"Song","year":"2019","journal-title":"Nano Lett"},{"issue":"12","key":"10.1016\/j.bj.2025.100870_bib16","first-page":"3962","article-title":"Exosomes derived from bone marrow mesenchymal stem cells improve osteoporosis through promoting osteoblast proliferation via MAPK pathway","volume":"22","author":"Zhao","year":"2018","journal-title":"Eur Rev Med Pharmacol Sci"},{"issue":"6","key":"10.1016\/j.bj.2025.100870_bib17","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jbiosc.2021.02.007","article-title":"Exosomes from adipose derived mesenchymal stem cells alleviate diabetic osteoporosis in rats through suppressing NLRP3 inflammasome activation in osteoclasts","volume":"131","author":"Zhang","year":"2021","journal-title":"J Biosci Bioeng"},{"key":"10.1016\/j.bj.2025.100870_bib18","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.jconrel.2023.11.020","article-title":"Pueraria lobata-derived exosome-like nanovesicles alleviate osteoporosis by enhacning autophagy","volume":"364","author":"Zhan","year":"2023","journal-title":"J Control Release"},{"issue":"43","key":"10.1016\/j.bj.2025.100870_bib19","doi-asserted-by":"crossref","first-page":"20884","DOI":"10.1039\/C9NR02791B","article-title":"Aptamer-functionalized exosomes from bone marrow stromal cells target bone to promote bone regeneration","volume":"11","author":"Luo","year":"2019","journal-title":"Nanoscale"},{"issue":"1","key":"10.1016\/j.bj.2025.100870_bib20","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s43141-023-00539-0","article-title":"Early diagnostic and prognostic biomarkers for gastric cancer: systems-level molecular basis of subsequent alterations in gastric mucosa from chronic atrophic gastritis to gastric cancer","volume":"21","author":"Selvan","year":"2023","journal-title":"J Genet Eng Biotechnol"},{"issue":"6","key":"10.1016\/j.bj.2025.100870_bib21","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3390\/medicina54060098","article-title":"Biological activities of lactose-based prebiotics and symbiosis with probiotics on controlling osteoporosis, blood-lipid and glucose levels","volume":"54","author":"Nath","year":"2018","journal-title":"Medicina (Kaunas)"},{"issue":"47","key":"10.1016\/j.bj.2025.100870_bib22","doi-asserted-by":"crossref","first-page":"E7554","DOI":"10.1073\/pnas.1607235113","article-title":"Gut microbiota induce IGF-1 and promote bone formation and growth","volume":"113","author":"Yan","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"10.1016\/j.bj.2025.100870_bib23","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s13105-021-00837-6","article-title":"Effects of gut microbiota-derived extracellular vesicles on obesity and diabetes and their potential modulation through diet","volume":"78","author":"Diez-Sainz","year":"2022","journal-title":"J Physiol Biochem"},{"key":"10.1016\/j.bj.2025.100870_bib24","doi-asserted-by":"crossref","DOI":"10.7717\/peerj.3450","article-title":"Diversity analysis of gut microbiota in osteoporosis and osteopenia patients","volume":"5","author":"Wang","year":"2017","journal-title":"PeerJ"},{"issue":"9","key":"10.1016\/j.bj.2025.100870_bib25","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.1002\/fsn3.1824","article-title":"Lactobacillus fermentum ZS40 prevents secondary osteoporosis in wistar rat","volume":"8","author":"Liu","year":"2020","journal-title":"Food Sci Nutr"},{"key":"10.1016\/j.bj.2025.100870_bib26","doi-asserted-by":"crossref","first-page":"581","DOI":"10.2217\/fmb-2022-0211","article-title":"Lactobacillus acidophilus supernatant alleviates osteoporosis by upregulating colonic SERT expression","volume":"18","author":"Zhai","year":"2023","journal-title":"Future Microbiol"},{"issue":"1","key":"10.1016\/j.bj.2025.100870_bib27","doi-asserted-by":"crossref","DOI":"10.1080\/19490976.2023.2190304","article-title":"Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17\/Treg balance and gut microbiota structure","volume":"15","author":"Guo","year":"2023","journal-title":"Gut Microbes"},{"key":"10.1016\/j.bj.2025.100870_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2022.116483","article-title":"Bilirubin increases viability and decreases osteoclast apoptosis contributing to osteoporosis in advanced liver diseases","volume":"162","author":"Jurado","year":"2022","journal-title":"Bone"},{"issue":"6","key":"10.1016\/j.bj.2025.100870_bib29","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1172\/JCI117959","article-title":"Role of hyperbilirubinemia in the impairment of osteoblast proliferation associated with cholestatic jaundice","volume":"95","author":"Janes","year":"1995","journal-title":"J Clin Invest"},{"key":"10.1016\/j.bj.2025.100870_bib30","article-title":"Exercise for osteoporosis: a literature review of pathology and mechanism","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Immunol"},{"issue":"1","key":"10.1016\/j.bj.2025.100870_bib31","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13287-023-03317-4","article-title":"Osteoporosis treatment using stem cell-derived exosomes: a systematic review and meta-analysis of preclinical studies","volume":"14","author":"He","year":"2023","journal-title":"Stem Cell Res Ther"},{"key":"10.1016\/j.bj.2025.100870_bib32","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41413-019-0058-7","article-title":"Autophagy in bone homeostasis and the onset of osteoporosis","volume":"7","author":"Yin","year":"2019","journal-title":"Bone Res"},{"issue":"10","key":"10.1016\/j.bj.2025.100870_bib33","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1080\/15548627.2021.2017587","article-title":"Degradation of the NOTCH intracellular domain by elevated autophagy in osteoblasts promotes osteoblast differentiation and alleviates osteoporosis","volume":"18","author":"Yoshida","year":"2022","journal-title":"Autophagy"},{"issue":"5","key":"10.1016\/j.bj.2025.100870_bib34","first-page":"3676","article-title":"Vitamin K2 stimulates MC3T3-E1 osteoblast differentiation and mineralization through autophagy induction","volume":"19","author":"Li","year":"2019","journal-title":"Mol Med Rep"},{"issue":"9","key":"10.1016\/j.bj.2025.100870_bib35","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1080\/15548627.2021.2016231","article-title":"Negative pressure wound therapy improves bone regeneration by promoting osteogenic differentiation via the AMPK-ULK1-autophagy axis","volume":"18","author":"Zhang","year":"2022","journal-title":"Autophagy"},{"issue":"8","key":"10.1016\/j.bj.2025.100870_bib36","doi-asserted-by":"crossref","DOI":"10.1002\/mbo3.810","article-title":"Microbial osteoporosis: the interplay between the gut microbiota and bones via host metabolism and immunity","volume":"8","author":"Li","year":"2019","journal-title":"MicrobiologyOpen"},{"issue":"3","key":"10.1016\/j.bj.2025.100870_bib37","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1021\/acs.jafc.8b05164","article-title":"Dietary fructooligosaccharide and glucomannan alter gut microbiota and improve bone metabolism in senescence-accelerated mouse","volume":"67","author":"Tanabe","year":"2019","journal-title":"J Agric Food Chem"},{"key":"10.1016\/j.bj.2025.100870_bib38","article-title":"Soy-whey dual-protein alleviates osteoporosis of ovariectomized rats via regulating bone fat metabolism through gut-liver-bone axis","volume":"103\u20134","author":"Zhang","year":"2022","journal-title":"Nutrition"},{"issue":"7","key":"10.1016\/j.bj.2025.100870_bib39","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202100451R","article-title":"Gut microbiota and bone metabolism","volume":"35","author":"Lu","year":"2021","journal-title":"FASEB J"},{"issue":"1","key":"10.1016\/j.bj.2025.100870_bib40","doi-asserted-by":"crossref","DOI":"10.1080\/19490976.2024.2437247","article-title":"Gut microbiota and microbial metabolites for osteoporosis","volume":"17","author":"Zheng","year":"2025","journal-title":"Gut Microbes"},{"issue":"1","key":"10.1016\/j.bj.2025.100870_bib41","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1080\/13880209.2022.2056208","article-title":"Gut microbiota and metabonomics used to explore the mechanism of Qing\u2019e Pills in alleviating osteoporosis","volume":"60","author":"Xie","year":"2022","journal-title":"Pharm Biol"},{"key":"10.1016\/j.bj.2025.100870_bib42","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bonr.2018.02.001","article-title":"Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in osteoporotic mice via modulating Treg-Th17 cell balance","volume":"8","author":"Dar","year":"2018","journal-title":"Bone Rep"},{"key":"10.1016\/j.bj.2025.100870_bib43","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1285442","article-title":"Lactobacillus plantarum attenuates glucocorticoid-induced osteoporosis by altering the composition of rat gut microbiota and serum metabolic profile","volume":"14","author":"Li","year":"2024","journal-title":"Front Immunol"},{"issue":"3","key":"10.1016\/j.bj.2025.100870_bib44","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/joim.12805","article-title":"Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial","volume":"284","author":"Nilsson","year":"2018","journal-title":"J Intern Med"},{"issue":"20","key":"10.1016\/j.bj.2025.100870_bib45","doi-asserted-by":"crossref","first-page":"23689","DOI":"10.18632\/aging.203641","article-title":"Analysis of gut microbiota and metabolites in patients with rheumatoid arthritis and identification of potential biomarkers","volume":"13","author":"Chen","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"10.1016\/j.bj.2025.100870_bib46","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2020.535310","article-title":"Fecal and serum metabolomic signatures and microbial community profiling of postmenopausal osteoporosis mice model","volume":"10","author":"Wen","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"issue":"11","key":"10.1016\/j.bj.2025.100870_bib47","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1111\/liv.14630","article-title":"Bilirubin and bile acids in osteocytes and bone tissue. Potential role in the cholestatic-induced osteoporosis","volume":"40","author":"Ruiz-Gaspa","year":"2020","journal-title":"Liver Int"},{"issue":"12","key":"10.1016\/j.bj.2025.100870_bib48","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1111\/eci.12355","article-title":"Ursodeoxycholic acid decreases bilirubin-induced osteoblast apoptosis","volume":"44","author":"Ruiz-Gaspa","year":"2014","journal-title":"Eur J Clin Invest"}],"container-title":["Biomedical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2319417025000447?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2319417025000447?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T20:27:37Z","timestamp":1776198457000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2319417025000447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["S2319417025000447"],"URL":"https:\/\/doi.org\/10.1016\/j.bj.2025.100870","relation":{},"ISSN":["2319-4170"],"issn-type":[{"value":"2319-4170","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Autophagy-induced osteoblast-derived exosomes maintain bone formation and prevent osteoporosis by remodeling gut microbiota-metabolism","name":"articletitle","label":"Article Title"},{"value":"Biomedical Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bj.2025.100870","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University.","name":"copyright","label":"Copyright"}],"article-number":"100870"}}