title: Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage.
abstract: Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats' articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway.
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.|Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Tan
authors.affiliation: UMR 7561 CNRS-Universitéde Lorraine, Faculté de Médicine, Vandoeuvre-lès-Nancy, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Magdalou
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.|Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
authors.forename: Liaobin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.|Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002110:Caffeine / Q000009:adverse effects*; D002358:Cartilage, Articular / Q000196:embryology / Q000378:metabolism* / Q000473:pathology*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D059305:Diet, High-Fat; D005260:Female; D005333:Fetus / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000473:pathology*; D017208:Rats, Wistar; D014886:Weaning; D015430:Weight Gain / Q000187:drug effects
chemical_list: D002110:Caffeine; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol