{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:05:16Z","timestamp":1791889516218,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Children's Hospital of Fudan University","award":["DGJFYJK01"],"award-info":[{"award-number":["DGJFYJK01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Epidemiological data suggest that various noncommunicable diseases develop as a result of altered maternal metabolic and physiological status due to exposure to several adverse factors during pregnancy. However, evidence for intrauterine exposure factors and mechanisms underlying the origin of early cartilage disease in chronic osteoarthritic disease is still lacking. In this study, we found that persistent overnutrition during pregnancy in obese mothers led to cartilage damage in neonatal male mice. This was mainly characterized by increased apoptosis with decreased expression of chondrocyte collagen II and low expression of Runx family transcription factor 2 (RUNX2) and SRY-box transcription factor 9 (SOX9). This reduction was also found to be associated with high leptin expression in newborn male mice of obese maternal offspring. Furthermore, the administration of leptin and mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) inhibitors in primary chondrocytes showed that leptin mediated MAPK\/ERK signaling activation and thus affected the key regulators of cartilage matrix metallopeptidase 1 (MMP1) and tissue inhibitor of metalloproteinase 1 (TIMP1), thereby altering the expression of collagen II in mouse cartilage. Altogether, this study provided insights into the molecular mechanisms of cartilage-related disease development and also new clues and evidence for the fetogenetic origin of cartilage diseases.<\/jats:p>","DOI":"10.3390\/biom12030477","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T13:24:59Z","timestamp":1647869099000},"page":"477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Effects of the Leptin-Mediated MAPK\/ERK Signaling Pathway on Collagen II Expression in Knee Cartilage of Newborn Male Mice from Obese Maternal Offspring"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8215-1034","authenticated-orcid":false,"given":"Wenji","family":"Wang","sequence":"first","affiliation":[{"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Fudan University, Shanghai 201102, China"},{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialing","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Fudan University, Shanghai 201102, China"},{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"},{"name":"Institute of Pediatrics, Children\u2019s Hospital, Fudan University, Shanghai 201102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huo","sequence":"additional","affiliation":[{"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Fudan University, Shanghai 201102, China"},{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanzheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Fudan University, Shanghai 201102, China"},{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghao","family":"Gui","sequence":"additional","affiliation":[{"name":"National Children\u2019s Medical Center, Children\u2019s Hospital, Fudan University, Shanghai 201102, China"},{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1136\/jech.58.2.114","article-title":"Developmental origins of adult health and disease","volume":"58","author":"Barker","year":"2004","journal-title":"J. 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