{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:28:42Z","timestamp":1785184122782,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG46927"],"award-info":[{"award-number":["AG46927"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Obesity and osteoarthritis (OA) are 2 major public health issues affecting millions of people worldwide. Whereas parental obesity affects the predisposition to diseases such as cancer or diabetes in children, transgenerational influences on musculoskeletal conditions such as OA are poorly understood. This study was undertaken to assess the intergenerational effects of a parental\/grandparental high\u2010fat diet on the metabolic and skeletal phenotype, systemic inflammation, and predisposition to OA in 2 generations of offspring in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Metabolic phenotype and predisposition to OA were investigated in the first and second (F1 and F2) generations of offspring (n = 10\u201316 mice per sex per diet) bred from mice fed a high\u2010fat diet (HFD) or a low\u2010fat control diet. OA was induced by destabilizing the medial meniscus. OA, synovitis, and adipose tissue inflammation were determined histologically, while bone changes were measured using micro\u2013computed tomography. Serum and synovial cytokines were measured by multiplex assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Parental high\u2010fat feeding showed an intergenerational effect, with inheritance of increased weight gain (up to 19% in the F1 generation and 9% in F2), metabolic imbalance, and injury\u2010induced OA in at least 2 generations of mice, despite the fact that the offspring were fed the low\u2010fat diet. Strikingly, both F1 and F2 female mice showed an increased predisposition to injury\u2010induced OA (48% higher predisposition in F1 and 19% in F2 female mice fed the HFD) and developed bone microarchitectural changes that were attributable to parental and grandparental high\u2010fat feeding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of this study reveal a detrimental effect of parental HFD and obesity on the musculoskeletal integrity of 2 generations of offspring, indicating the importance of further investigation of these effects. An improved understanding of the mechanisms involved in the transmissibility of diet\u2010induced changes through multiple generations may help in the development of future therapies that would target the effects of obesity on OA and related conditions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41147","type":"journal-article","created":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T12:18:56Z","timestamp":1571919536000},"page":"632-644","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Intergenerational Transmission of Diet\u2010Induced Obesity, Metabolic Imbalance, and Osteoarthritis in Mice"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2140-4157","authenticated-orcid":false,"given":"Natalia S.","family":"Harasymowicz","sequence":"first","affiliation":[{"name":"Washington University in St. Louis and Shriners Hospitals for Children  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Rak","family":"Choi","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis and Shriners Hospitals for Children, St. Louis, Missouri, and Yonsei University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Lung","family":"Wu","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis and Shriners Hospitals for Children  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"Iannucci","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis and Shriners Hospitals for Children  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhang","family":"Tang","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis and Shriners Hospitals for Children  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farshid","family":"Guilak","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis and Shriners Hospitals for Children  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61729-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-133-8-200010170-00016"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu464"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199806)41:6<1064::AID-ART13>3.0.CO;2-K"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205601"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33332"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/GRF.0b013e318299c39d"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816781116"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-016-0807-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.167.10.1068"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.005"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00017.2016"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2017.03.008"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00342"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043123"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.03.006"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22940"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34533"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2016.01.001"},{"key":"e_1_2_7_22_1","unstructured":"LittleD WuCL D'AmicoR CorcoranD GregoryS GuilakF.Epigenetic analysis of adipose stem cells in obesity identifies dysregulation of critical pathways in musculoskeletal regeneration and disease [poster]. 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