title: Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats.
abstract: Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotine exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis.
authors: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors: Yu
authors: Y
authors: Deng
authors: Hong
authors: H
authors: Cao
authors: Fenglong
authors: F
authors: Cu
authors: Dan
authors: D
authors: Xu
authors: Youying
authors: Y
authors: Lei
authors: Yang
authors: Y
authors: Tan
authors: Jacques
authors: J
authors: Magdalou
authors: Hui
authors: H
authors: Wang
authors: Liaobin
authors: L
authors: Chen
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020219:Chondrogenesis / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D020567:Fetal Weight / Q000187:drug effects; D005865:Gestational Age; D006132:Growth Plate / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D018722:Nicotinic Agonists; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; D009538:Nicotine; D003345:Corticosterone