PMID- 29981921
OWN - NLM
STAT- MEDLINE
DCOM- 20180829
LR  - 20180829
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 295
DP  - 2018 Oct 1
TI  - Prenatal nicotine exposure retards osteoclastogenesis and endochondral 
      ossification in fetal long bones in rats.
PG  - 249-255
LID - S0378-4274(18)31489-9 [pii]
LID - 10.1016/j.toxlet.2018.07.005 [doi]
AB  - This study investigated the mechanisms underlying the retarded development of 
      long bone in fetus by prenatal nicotine exposure (PNE) which had been 
      demonstrated by our previous work. Nicotine (2.0 mg/kg.d) or saline was injected 
      subcutaneously into pregnant rats every morning from gestational day (GD) 9 to 
      20. Fetal femurs or tibias were harvested for analysis on GD 20. We found massive 
      accumulation of hypertrophic chondrocytes and a delayed formation of primary 
      ossification center (POC) in the fetal femur or tibia of rat fetus after PNE, 
      which was accompanied by a decreased amount of osteoclasts in the POC and 
      up-regulated expression of osteoprotegerin (OPG) but by no obvious change in the 
      expression of receptor activator of NF-kappaB ligand (RANKL). In primary osteoblastic 
      cells, both nicotine (0, 162, 1620, 16,200 ng/ml) and corticosterone (0, 50, 250, 
      1250 nM) promoted the mRNA expression of OPG but concentration-dependently 
      suppressed that of RANKL. Furthermore, blocking alpha4beta2-nicotinic acetylcholine 
      receptor (alpha4beta2-nAChR) or glucocorticoid receptor rescued the above effects of 
      nicotine and corticosterone, respectively. In conclusion, retarded 
      osteoclastogenesis may contribute to delayed endochondral ossification in long 
      bone in fetal rats with PNE. The adverse effects of PNE may be mediated via the 
      direct effect of nicotine and indirect effect of maternal corticosterone on 
      osteoblastic cells.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Hu, Hang
AU  - Hu H
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Hubei 
      Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, 
      China; Department of Physiology, Basic Medical School of Wuhan University, Wuhan 
      430071, China.
FAU - Zhao, Xin
AU  - Zhao X
AD  - Department of Physiology, Basic Medical School of Wuhan University, Wuhan 430071, 
      China.
FAU - Ma, Jing
AU  - Ma J
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Hubei 
      Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, 
      China; Department of Physiology, Basic Medical School of Wuhan University, Wuhan 
      430071, China.
FAU - Shangguan, Yangfan
AU  - Shangguan Y
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Hubei 
      Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, 
      China; Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, 
      Wuhan 430071, China.
FAU - Pan, Zhengqi
AU  - Pan Z
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Hubei 
      Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, 
      China; Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, 
      Wuhan 430071, China.
FAU - Chen, Liaobin
AU  - Chen L
AD  - Department of Orthopaedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China.
FAU - Zhang, Xianrong
AU  - Zhang X
AD  - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical 
      University, Guangdong Provincial Key Laboratory of Bone and Cartilage 
      Regenerative Medicine, Nanfang Hospital, Southern Medical University, No.1838 
      North of Guangzhou Avenue, Guangzhou, 510515, China. Electronic address: 
      xianrongzh@smu.edu.cn.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Hubei 
      Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, 
      China. Electronic address: wanghui19@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20180705
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Osteoprotegerin)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (Tnfrsf11b protein, rat)
RN  - 0 (nicotinic receptor alpha4beta2)
RN  - 6M3C89ZY6R (Nicotine)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Bone Development/*drug effects
MH  - Cells, Cultured
MH  - Chondrocytes/drug effects/metabolism/pathology
MH  - Corticosterone/toxicity
MH  - Female
MH  - Femur/*drug effects/embryology/metabolism
MH  - Gestational Age
MH  - Maternal Exposure/adverse effects
MH  - Nicotine/*toxicity
MH  - Nicotinic Agonists/*toxicity
MH  - Osteoclasts/drug effects/metabolism/pathology
MH  - Osteogenesis/*drug effects
MH  - Osteoprotegerin/metabolism
MH  - Pregnancy
MH  - RANK Ligand/metabolism
MH  - Rats, Wistar
MH  - Receptors, Glucocorticoid/metabolism
MH  - Receptors, Nicotinic/metabolism
MH  - Tibia/*drug effects/embryology/metabolism
OTO - NOTNLM
OT  - Endochondral ossification
OT  - Nicotine
OT  - Osteoclastogenesis
OT  - Prenatal exposure
EDAT- 2018/07/10 06:00
MHDA- 2018/08/30 06:00
CRDT- 2018/07/09 06:00
PHST- 2017/11/14 00:00 [received]
PHST- 2018/06/06 00:00 [revised]
PHST- 2018/07/04 00:00 [accepted]
PHST- 2018/07/10 06:00 [pubmed]
PHST- 2018/08/30 06:00 [medline]
PHST- 2018/07/09 06:00 [entrez]
AID - S0378-4274(18)31489-9 [pii]
AID - 10.1016/j.toxlet.2018.07.005 [doi]
PST - ppublish
SO  - Toxicol Lett. 2018 Oct 1;295:249-255. doi: 10.1016/j.toxlet.2018.07.005. Epub 
      2018 Jul 5.