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 ă intrauterine growth retardation (IUGR) and skeletal growth retardation. ă Among a multitude of chemicals associated with cigarette smoking, ă nicotine is one of the leading candidates for causing low birth weights. ă However, the possible mechanism of delayed chondrogenesis by prenatal ă nicotine exposure remains unclear. We investigated the effects of ă nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats ă were given 2.0 mg/kg . d of nicotine subcutaneously from gestational ă days 11 to 20. Prenatal nicotine exposure increased the levels of fetal ă blood corticosterone and resulted in fetal skeletal growth retardation. ă Moreover, nicotine exposure induced the inhibition of matrix synthesis ă and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in ă fetal growth plates. The effects of nicotine on growth plates were ă studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, ă 10, or 100 mu M of nicotine for 10 days. Nicotine inhibited matrix ă synthesis and down-regulated IGF-1 signaling in chondrocytes in a ă concentration-dependent manner. These results suggest that prenatal ă nicotine exposure induces delayed chondrogenesis and that the mechanism ă may involve the down-regulation of IGF-1 signaling and the inhibition of ă matrix synthesis by growth plate chondrocytes. The present study aids in ă the characterization of delayed chondrogenesis caused by prenatal ă nicotine exposure, which might suggest a candidate mechanism for ă intrauterine origins of osteoporosis and osteoarthritis. (C) 2013 ă Elsevier Inc. All rights reserved.
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Toxicology and Applied Pharmacology, Elsevier, 2013, 269 (1), pp.25-33. 〈10.1016/j.taap.2013.02.008〉
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Soumis le : vendredi 10 février 2017 - 13:23:52
Dernière modification le : jeudi 11 janvier 2018 - 06:25:37

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Yu Deng, Hong Cao, Fenglong Cu, Dan Xu, Youying Lei, et al.. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats. Toxicology and Applied Pharmacology, Elsevier, 2013, 269 (1), pp.25-33. 〈10.1016/j.taap.2013.02.008〉. 〈hal-01464672〉

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