title: Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway.
abstract: Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.|Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors.forename: Qubo
authors.initials: Q
authors.lastname: Ni
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: Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
authors.forename: Xianrong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Université de Lorraine, Ingénierie Moléculaire, Physiopathologie Articulaire (IMoPA), UMR 7365 CNRS, Biopôle, F-54505 Vandœuvre-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: D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D004198:Disease Susceptibility; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood* / Q000139:chemically induced; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007596:Joints / Q000473:pathology; D008297:Male; D010003:Osteoarthritis / Q000097:blood* / Q000139:chemically induced; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood* / Q000139:chemically induced; D017208:Rats, Wistar; D012420:Running; D015398:Signal Transduction
chemical_list: C548904:insulin-like growth factor-1, rat; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D003345:Corticosterone