PMID- 27128203
OWN - NLM
STAT- MEDLINE
DCOM- 20171017
LR  - 20210109
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 173
IP  - 14
DP  - 2016 Jul
TI  - Mitogen-inducible gene-6 partly mediates the inhibitory effects of prenatal 
      dexamethasone exposure on endochondral ossification in long bones of fetal rats.
PG  - 2250-62
LID - 10.1111/bph.13506 [doi]
AB  - BACKGROUND AND PURPOSE: Prenatal exposure to dexamethasone slows down fetal 
      linear growth and bone mineralization but the regulatory mechanism remains 
      unknown. Here we assessed how dexamethasone regulates bone development in the 
      fetus. EXPERIMENTAL APPROACH: Dexamethasone (1 mg.kg(-1) .day(-1) ) was injected 
      subcutaneously every morning in pregnant rats from gestational day (GD)9 to GD20. 
      Fetal femurs and tibias were harvested at GD20 for histological and gene 
      expression analysis. Femurs of 12-week-old female offspring were harvested for 
      microCT (muCT) measurement. Primary chondrocytes were treated with dexamethasone 
      (10, 50, 250 and 1000 nM). KEY RESULTS: Prenatal dexamethasone exposure resulted 
      in accumulation of hypertrophic chondrocytes and delayed formation of the primary 
      ossification centre in fetal long bone. The retardation was accompanied by 
      reduced maturation of hypertrophic chondrocytes, decreased osteoclast number and 
      down-regulated expression of osteocalcin and bone sialoprotein in long bone. In 
      addition, the mitogen-inducible gene-6 (Mig6) and osteoprotegerin (OPG) 
      expression were stimulated, and the receptor activator of NF-kappaB ligand (RANKL) 
      expression was repressed. Moreover, dexamethasone activated OPG and repressed 
      RANKL expression in both primary chondrocytes and primary osteoblasts, and the 
      knockdown of Mig6 abolished the effect of dexamethasone on OPG expression. 
      Further, muCT measurement showed loss of bone mass in femur of 12-week-old 
      offspring with prenatal dexamethasone exposure. CONCLUSIONS AND IMPLICATIONS: 
      Prenatal dexamethasone exposure delays endochondral ossification by suppressing 
      chondrocyte maturation and osteoclast differentiation, which may be partly 
      mediated by Mig6 activation in bone. Bone development retardation in the fetus 
      may be associated with reduced bone mass in later life.
CI  - (c) 2016 The British Pharmacological Society.
FAU - Zhang, Xianrong
AU  - Zhang X
AD  - Department of Physiology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
FAU - Shang-Guan, Yangfan
AU  - Shang-Guan Y
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 
      China.
FAU - Ma, Jing
AU  - Ma J
AD  - Department of Physiology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
FAU - Hu, Hang
AU  - Hu H
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 
      China.
FAU - Wang, Linlong
AU  - Wang L
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 
      China.
FAU - Magdalou, Jacques
AU  - Magdalou J
AD  - Faculte de Medicine, UMR 7561 CNRS-NancyUniversite, Vandoeuvre-les-Nancy, France.
FAU - Chen, Liaobin
AU  - Chen L
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 
      China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20160602
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Carrier Proteins)
RN  - 0 (Errfi1 protein, rat)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Bone and Bones/*drug effects/metabolism
MH  - Carrier Proteins/genetics/*metabolism
MH  - Dexamethasone/administration & dosage/*toxicity
MH  - Female
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Osteogenesis/*drug effects
MH  - Pregnancy
MH  - Rats
MH  - Rats, Wistar
PMC - PMC4919583
EDAT- 2016/04/30 06:00
MHDA- 2017/10/19 06:00
PMCR- 2017/07/01
CRDT- 2016/04/30 06:00
PHST- 2015/09/15 00:00 [received]
PHST- 2016/04/05 00:00 [revised]
PHST- 2016/04/18 00:00 [accepted]
PHST- 2016/04/30 06:00 [entrez]
PHST- 2016/04/30 06:00 [pubmed]
PHST- 2017/10/19 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - BPH13506 [pii]
AID - 10.1111/bph.13506 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2016 Jul;173(14):2250-62. doi: 10.1111/bph.13506. Epub 2016 Jun 
      2.