Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring.
This study aimed to evaluate whether female adult offspring born with intrauterine growth retardation induced by prenatal nicotine exposure (PNE) are susceptible to osteoarthritis (OA) and to explore the underlying programming mechanisms. Pregnant rats were treated with nicotine or saline at 2.0 mg/kg/d from gestational d 11 to 20. The female adult offspring with or without PNE were forced with a strenuous treadmill running for 6 wk to induce OA. Nicotine's effects on fetal articular chondrocytes were studied by exposing chondrocytes to nicotine for 10 d, and dihydro-β-erythroidine, a selective α4β2-nicotinic acetylcholine receptor (nAChR) inhibitor, was used to identify the change of nicotine's effect. For adult offspring, increased cartilage destruction and accelerated OA progression were observed in the PNE group with running; the expression of α1 chain of type II collagen (Col2A1), aggrecan, SRY-type high mobility group box 9 (Sox9), and IGF1 signaling molecules in the cartilage of PNE offspring were decreased. For fetuses, elevated serum corticosteroid and nicotine levels and suppressed IGF1 levels were observed; expression of Col2A1, aggrecan, Sox9, and IGF1 were reduced. The result of chondrocytes revealed that nicotine impeded the expression of Col2A1, aggrecan, and IGF1; blocking α4β2-nAChR rescued nicotine's suppression. In conclusion, PNE increases the susceptibility of adult offspring to OA; the potential mechanism involves IGF1 low-functional programming in articular cartilage caused directly by the action of nicotine on α4β2-nAChR.
*Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Physiology and Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China; and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China.
Kai
K
Tie
*Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Physiology and Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China; and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China.
Xianrong
X
Zhang
*Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Physiology and Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China; and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China.
Yang
Y
Tan
*Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Physiology and Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China; and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China.
Yu
Y
Deng
*Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Physiology and Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China; and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China.
Jing
J
Li
*Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Physiology and Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China; and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China.
Qubo
Q
Ni
*Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Physiology and Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China; and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China wanghui19@whu.edu.cn lbchen@whu.edu.cn.
Hui
H
Wang
*Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Physiology and Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China; and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China wanghui19@whu.edu.cn lbchen@whu.edu.cn.
Liaobin
L
Chen
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D004198:Disease Susceptibility; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D018811:Maternal Exposure / Q000009:adverse effects*; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology; D010003:Osteoarthritis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; D009538:Nicotine
Sox9; articular cartilage; extracellular matrix; glucocorticoid