PMID- 27338645
OWN - NLM
STAT- MEDLINE
DCOM- 20170529
LR  - 20180103
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 305
DP  - 2016 Aug 15
TI  - Suppressed osteoclast differentiation at the chondro-osseous junction mediates 
      endochondral ossification retardation in long bones of Wistar fetal rats with 
      prenatal ethanol exposure.
PG  - 234-241
LID - S0041-008X(16)30155-7 [pii]
LID - 10.1016/j.taap.2016.06.021 [doi]
AB  - Prenatal ethanol exposure (PEE) inhibits longitudinal growth of fetal bones, but 
      the underlying mechanisms remain unknown. In this study, we aimed to investigate 
      how PEE induces the retardation of long bone development in fetal rats. Pregnant 
      Wistar rats were treated with ethanol or distilled water (control group) by 
      gavage from gestational day (GD) 9 to 20. Fetuses were delivered by cesarean 
      section on GD20. Fetal sera were collected for assessing corticosterone (CORT) 
      level. Fetal long bones were harvested for histochemical, immunohistochemical and 
      gene expression analysis. Primary chondrocytes were treated with ethanol or CORT 
      for analyzing genes expression. PEE fetuses showed a significant reduction in 
      birth weight and body length. The serum CORT concentration in PEE group was 
      significantly increased, while the body weight, body length and femur length all 
      were significantly decreased in the PEE group. The length of the epiphyseal 
      hypertrophy zone was enlarged, whereas the length of the primary ossification 
      center was significantly reduced in PEE fetuses. TUNEL assay showed reduced 
      apoptosis in the PEE group. Further, the gene expression of osteoprotegerin (OPG) 
      was markedly up-regulated. In vitro experiments showed that CORT (but not 
      ethanol) treatment significantly activated the expression of OPG, while the 
      application of glucocorticoid receptor inhibitor, mifepristone, attenuated these 
      change induced by CORT. These results indicated that PEE-induced glucocorticoid 
      over-exposure enhanced the expression of OPG in fetal epiphyseal cartilage and 
      further lead to the suppressed osteoclast differentiation in the chondro-osseous 
      junction and consequently inhibited the endochondral ossification in long bones 
      of fetal rats.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Pan, Zhengqi
AU  - Pan Z
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China; Department of Pharmacology, Basic Medical School of Wuhan 
      University, Wuhan 430071, China.
FAU - Zhang, Xianrong
AU  - Zhang X
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 
      430071, China.
FAU - Shangguan, Yangfan
AU  - Shangguan Y
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China.
FAU - Hu, Hang
AU  - Hu H
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China.
FAU - Chen, Liaobin
AU  - Chen L
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China. Electronic address: lbchen@whu.edu.cn.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160623
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Chondrocytes/drug effects/physiology
MH  - Ethanol/*toxicity
MH  - Female
MH  - Femur/*drug effects/growth & development
MH  - Fetus
MH  - Osteoclasts/drug effects/physiology
MH  - Osteogenesis/*drug effects
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Endochondral ossification retardation
OT  - Osteoclast
OT  - Osteoprotegerin (OPG)
OT  - Prenatal ethanol exposure
OT  - Receptor activator for nuclear factor-kappab ligand (RANKL)
EDAT- 2016/06/25 06:00
MHDA- 2017/05/30 06:00
CRDT- 2016/06/25 06:00
PHST- 2016/04/12 00:00 [received]
PHST- 2016/06/17 00:00 [revised]
PHST- 2016/06/18 00:00 [accepted]
PHST- 2016/06/25 06:00 [entrez]
PHST- 2016/06/25 06:00 [pubmed]
PHST- 2017/05/30 06:00 [medline]
AID - S0041-008X(16)30155-7 [pii]
AID - 10.1016/j.taap.2016.06.021 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2016 Aug 15;305:234-241. doi: 10.1016/j.taap.2016.06.021. 
      Epub 2016 Jun 23.