{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:41:52Z","timestamp":1789576912851,"version":"build-2803163510"},"reference-count":50,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR068061"],"award-info":[{"award-number":["AR068061"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","oarsijournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Osteoarthritis and Cartilage"],"published-print":{"date-parts":[[2019,1]]},"DOI":"10.1016\/j.joca.2018.07.020","type":"journal-article","created":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T13:41:59Z","timestamp":1537278119000},"page":"129-139","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":105,"title":["The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis"],"prefix":"10.1016","volume":"27","author":[{"given":"J.D.","family":"Guss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.N.","family":"Ziemian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Luna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.N.","family":"Sandoval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.T.","family":"Holyoak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.G.","family":"Guisado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Roubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2120-7487","authenticated-orcid":false,"given":"R.L.","family":"Callahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.L.","family":"Brito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6637-9808","authenticated-orcid":false,"given":"M.C.H.","family":"van der Meulen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.R.","family":"Goldring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0712-6533","authenticated-orcid":false,"given":"C.J.","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.joca.2018.07.020_bib1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nrrheum.2010.123","article-title":"Obesity punches above its weight in osteoarthritis","volume":"7","author":"Aspden","year":"2011","journal-title":"Nat Rev Rheumatol"},{"issue":"11","key":"10.1016\/j.joca.2018.07.020_bib2","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1016\/j.joca.2015.05.016","article-title":"Metabolic stress-induced joint inflammation and osteoarthritis","volume":"23","author":"Courties","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"key":"10.1016\/j.joca.2018.07.020_bib3","doi-asserted-by":"crossref","DOI":"10.1136\/ard.2005.045724","article-title":"Do metabolic factors add to the effect of overweight on hand osteoarthritis? The Rotterdam Study","volume":"66","author":"Dahaghin","year":"2007","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"10.1016\/j.joca.2018.07.020_bib4","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/ard.2008.106930","article-title":"Association between weight or body mass index and hand osteoarthritis: a systematic review","volume":"69","author":"Yusuf","year":"2010","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"10.1016\/j.joca.2018.07.020_bib5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3810\/pgm.2009.11.2073","article-title":"Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data","volume":"121","author":"Puenpatom","year":"2009","journal-title":"Postgrad Med J"},{"issue":"6","key":"10.1016\/j.joca.2018.07.020_bib6","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.jbspin.2013.09.007","article-title":"Is osteoarthritis a metabolic disease?","volume":"80","author":"Sellam","year":"2013","journal-title":"Jt Bone Spine"},{"issue":"11","key":"10.1016\/j.joca.2018.07.020_bib7","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.joca.2012.06.006","article-title":"Accumulation of metabolic risk factors such as overweight, hypertension, dyslipidaemia, and impaired glucose tolerance raises the risk of occurrence and progression of knee osteoarthritis: a 3-year follow-up of the ROAD study","volume":"20","author":"Yoshimura","year":"2012","journal-title":"Osteoarthritis Cartilage"},{"issue":"5","key":"10.1016\/j.joca.2018.07.020_bib8","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.jdiacomp.2016.02.016","article-title":"Type 2 diabetes and osteoarthritis: a systematic review and meta-analysis","volume":"30","author":"Williams","year":"2016","journal-title":"J\u00a0Diabetes Complicat"},{"issue":"2","key":"10.1016\/j.joca.2018.07.020_bib9","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2337\/dc12-0924","article-title":"Diabetes is an independent predictor for severe osteoarthritis: results from a longitudinal cohort study","volume":"36","author":"Schett","year":"2013","journal-title":"Diabetes Care"},{"issue":"1","key":"10.1016\/j.joca.2018.07.020_bib10","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2015-000077","article-title":"Association between diabetes mellitus and osteoarthritis: systematic literature review and meta-analysis","volume":"1","author":"Louati","year":"2015","journal-title":"RMD Open"},{"issue":"4","key":"10.1016\/j.joca.2018.07.020_bib11","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.semarthrit.2013.07.013","article-title":"Incidence of total knee and hip replacement for osteoarthritis in relation to the metabolic syndrome and its components: a prospective cohort study","volume":"43","author":"Monira Hussain","year":"2014","journal-title":"Semin Arthritis Rheum"},{"issue":"4","key":"10.1016\/j.joca.2018.07.020_bib12","doi-asserted-by":"crossref","first-page":"R130","DOI":"10.1186\/ar3068","article-title":"Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice","volume":"12","author":"Griffin","year":"2010","journal-title":"Arthritis Res Ther"},{"issue":"10","key":"10.1016\/j.joca.2018.07.020_bib13","doi-asserted-by":"crossref","first-page":"3220","DOI":"10.1002\/art.34533","article-title":"Diet-induced obesity significantly increases the severity of post-traumatic arthritis in mice","volume":"64","author":"Louer","year":"2012","journal-title":"Arthritis Rheum"},{"issue":"6","key":"10.1016\/j.joca.2018.07.020_bib14","doi-asserted-by":"crossref","first-page":"R198","DOI":"10.1186\/ar3529","article-title":"High-fat diet accelerates progression of osteoarthritis after meniscal\/ligamentous injury","volume":"13","author":"Mooney","year":"2011","journal-title":"Arthritis Res Ther"},{"issue":"12","key":"10.1016\/j.joca.2018.07.020_bib15","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1016\/j.joca.2016.06.019","article-title":"Diabetes-accelerated experimental osteoarthritis is prevented by autophagy activation","volume":"24","author":"Ribeiro","year":"2016","journal-title":"Osteoarthritis Cartilage"},{"issue":"10","key":"10.1016\/j.joca.2018.07.020_bib16","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1002\/art.24854","article-title":"Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis","volume":"60","author":"Griffin","year":"2009","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.joca.2018.07.020_bib17","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/978-1-61779-430-8_27","article-title":"A\u00a0mouse model of diet-induced obesity and insulin resistance","volume":"821","author":"Wang","year":"2012","journal-title":"Methods Mol Biol"},{"issue":"3","key":"10.1016\/j.joca.2018.07.020_bib18","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/j.1476-5381.2012.01911.x","article-title":"The use of animal models in diabetes research","volume":"166","author":"King","year":"2012","journal-title":"Br J Pharmacol"},{"issue":"Suppl C","key":"10.1016\/j.joca.2018.07.020_bib19","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.lfs.2015.05.025","article-title":"Leptin in osteoarthritis: focus on articular cartilage and chondrocytes","volume":"140","author":"Scotece","year":"2015","journal-title":"Life Sci"},{"issue":"11","key":"10.1016\/j.joca.2018.07.020_bib20","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1002\/art.11303","article-title":"Evidence for a key role of leptin in osteoarthritis","volume":"48","author":"Dumond","year":"2003","journal-title":"Arthritis Rheum"},{"issue":"6","key":"10.1016\/j.joca.2018.07.020_bib21","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1172\/JCI58109","article-title":"Gut microbiome, obesity, and metabolic dysfunction","volume":"121","author":"Tilg","year":"2011","journal-title":"J\u00a0Clin Invest"},{"issue":"1","key":"10.1016\/j.joca.2018.07.020_bib22","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/MOG.0000000000000139","article-title":"The gut microbiome in health and in disease","volume":"31","author":"Shreiner","year":"2015","journal-title":"Curr Opin Gastroenterol"},{"issue":"5975","key":"10.1016\/j.joca.2018.07.020_bib23","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.1179721","article-title":"Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5","volume":"328","author":"Vijay-Kumar","year":"2010","journal-title":"Science"},{"issue":"6","key":"10.1016\/j.joca.2018.07.020_bib24","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1002\/art.37906","article-title":"In\u00a0vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae","volume":"65","author":"Ko","year":"2013","journal-title":"Arthritis Rheum"},{"issue":"7","key":"10.1016\/j.joca.2018.07.020_bib25","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/jbmr.141","article-title":"Guidelines for assessment of bone microstructure in rodents using micro-computed tomography","volume":"25","author":"Bouxsein","year":"2010","journal-title":"J\u00a0Bone Miner Res"},{"issue":"Suppl 3","key":"10.1016\/j.joca.2018.07.020_bib26","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","article-title":"The OARSI histopathology initiative \u2013 recommendations for histological assessments of osteoarthritis in the mouse","volume":"18","author":"Glasson","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"issue":"9","key":"10.1016\/j.joca.2018.07.020_bib27","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1002\/art.11233","article-title":"Osteoarthritis-like changes and decreased mechanical function of articular cartilage in the joints of mice with the chondrodysplasia gene (cho)","volume":"48","author":"Xu","year":"2003","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.joca.2018.07.020_bib28","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1038\/ismej.2012.8","article-title":"Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms","volume":"6","author":"Caporaso","year":"2012","journal-title":"ISME J"},{"issue":"1","key":"10.1016\/j.joca.2018.07.020_bib29","doi-asserted-by":"crossref","DOI":"10.1128\/mSystems.00009-15","article-title":"Improved bacterial 16S rRNA gene (V4 and V4-5) and fungal internal transcribed spacer marker gene primers for microbial community surveys","volume":"1","author":"Walters","year":"2016","journal-title":"mSystems"},{"issue":"5","key":"10.1016\/j.joca.2018.07.020_bib30","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat Methods"},{"key":"10.1016\/j.joca.2018.07.020_bib31","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: high-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat Methods"},{"issue":"2","key":"10.1016\/j.joca.2018.07.020_bib32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/13684730050515796","article-title":"Interleukin\u20136 and interleukin\u20138 levels in serum and synovial fluid of patients with osteoarthritis","volume":"6","author":"Kaneko","year":"2000","journal-title":"Cytokines Cell Mol Ther"},{"key":"10.1016\/j.joca.2018.07.020_bib33","doi-asserted-by":"crossref","first-page":"D694","DOI":"10.2741\/Martel","article-title":"Cytokines and their role in the pathophysiology of osteoarthritis","volume":"4","author":"Martel-Pelletier","year":"1999","journal-title":"Front Biosci"},{"key":"10.1016\/j.joca.2018.07.020_bib34","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrrheum.2015.158","article-title":"Does lipopolysaccharide-mediated inflammation have a role in OA?","volume":"12","author":"Huang","year":"2015","journal-title":"Nat Rev Rheumatol"},{"issue":"10","key":"10.1016\/j.joca.2018.07.020_bib35","doi-asserted-by":"crossref","first-page":"e47713","DOI":"10.1371\/journal.pone.0047713","article-title":"High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway","volume":"7","author":"Kim","year":"2012","journal-title":"PLoS One"},{"issue":"10","key":"10.1016\/j.joca.2018.07.020_bib36","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1016\/j.joca.2016.05.008","article-title":"Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation","volume":"24","author":"Huang","year":"2016","journal-title":"Osteoarthr Cartilage"},{"issue":"3","key":"10.1016\/j.joca.2018.07.020_bib37","doi-asserted-by":"crossref","first-page":"319","DOI":"10.5312\/wjo.v5.i3.319","article-title":"Adipokines: biomarkers for osteoarthritis?","volume":"5","author":"Poonpet","year":"2014","journal-title":"World J Orthop"},{"issue":"10","key":"10.1016\/j.joca.2018.07.020_bib38","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1177\/0363546507307396","article-title":"The long-term consequence of anterior cruciate ligament and meniscus injuries","volume":"35","author":"Lohmander","year":"2007","journal-title":"Am J Sports Med"},{"issue":"1","key":"10.1016\/j.joca.2018.07.020_bib39","doi-asserted-by":"crossref","first-page":"475","DOI":"10.4049\/jimmunol.1102977","article-title":"TLR5, a novel and unidentified inflammatory mediator in rheumatoid arthritis that correlates with disease activity score and joint TNF-\u03b1 levels","volume":"189","author":"Chamberlain","year":"2012","journal-title":"J\u00a0Immunol"},{"issue":"7","key":"10.1016\/j.joca.2018.07.020_bib40","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1002\/art.21122","article-title":"Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial","volume":"52","author":"Brandt","year":"2005","journal-title":"Arthritis Rheum"},{"issue":"10","key":"10.1016\/j.joca.2018.07.020_bib41","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1002\/art.1780351007","article-title":"Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline","volume":"35","author":"Yu","year":"1992","journal-title":"Arthritis Rheum"},{"issue":"9","key":"10.1016\/j.joca.2018.07.020_bib42","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1002\/jbmr.2887","article-title":"Links between the microbiome and bone","volume":"31","author":"Hernandez","year":"2016","journal-title":"J\u00a0Bone Miner Res"},{"issue":"3","key":"10.1016\/j.joca.2018.07.020_bib43","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3109\/10408363.2015.1123215","article-title":"Chasing a ghost? \u2013 Issues with the determination of circulating levels of endotoxin in human blood","volume":"53","author":"Gnauck","year":"2016","journal-title":"Crit Rev Clin Lab Sci"},{"key":"10.1016\/j.joca.2018.07.020_bib44","doi-asserted-by":"crossref","DOI":"10.1038\/bonekey.2014.119","article-title":"Osteoarthritis and bone mineral density: are strong bones bad for joints","volume":"4","author":"Hardcastle","year":"2015","journal-title":"Bonekey Rep"},{"key":"10.1016\/j.joca.2018.07.020_bib45","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/jor.23731","article-title":"Collagen XI mutation lowers susceptibility to load-induced cartilage damage in mice","volume":"36","author":"Holyoak","year":"2018","journal-title":"J\u00a0Orthop Res"},{"issue":"1","key":"10.1016\/j.joca.2018.07.020_bib46","doi-asserted-by":"crossref","first-page":"5931","DOI":"10.1038\/s41598-018-24258-6","article-title":"The effect of ageing and osteoarthritis on the mechanical properties of cartilage and bone in the human knee joint","volume":"8","author":"Peters","year":"2018","journal-title":"Sci Rep"},{"issue":"6","key":"10.1016\/j.joca.2018.07.020_bib47","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/jbmr.3114","article-title":"Alterations to the gut microbiome impair bone strength and tissue material properties","volume":"32","author":"Guss","year":"2017","journal-title":"J\u00a0Bone Miner Res"},{"issue":"12","key":"10.1016\/j.joca.2018.07.020_bib48","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1016\/j.joca.2017.08.016","article-title":"Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice","volume":"25","author":"Adebayo","year":"2017","journal-title":"Osteoarthritis Cartilage"},{"issue":"8","key":"10.1016\/j.joca.2018.07.020_bib49","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.95997","article-title":"Targeting the gut microbiome to treat the osteoarthritis of obesity","volume":"3","author":"Schott","year":"2018","journal-title":"JCI Insight"},{"issue":"9","key":"10.1016\/j.joca.2018.07.020_bib50","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.joca.2007.03.006","article-title":"The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129\/SvEv mouse","volume":"15","author":"Glasson","year":"2007","journal-title":"Osteoarthritis Cartilage"}],"container-title":["Osteoarthritis and Cartilage"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1063458418314614?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1063458418314614?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T03:49:33Z","timestamp":1761018573000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1063458418314614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["S1063458418314614"],"URL":"https:\/\/doi.org\/10.1016\/j.joca.2018.07.020","relation":{},"ISSN":["1063-4584"],"issn-type":[{"value":"1063-4584","type":"print"}],"subject":[],"published":{"date-parts":[[2019,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis","name":"articletitle","label":"Article Title"},{"value":"Osteoarthritis and Cartilage","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.joca.2018.07.020","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}