PMID- 29966748
OWN - NLM
STAT- MEDLINE
DCOM- 20180829
LR  - 20180829
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 295
DP  - 2018 Oct 1
TI  - Prenatal caffeine exprosure increases adult female offspring rat's susceptibility 
      to osteoarthritis via low-functional programming of cartilage IGF-1 with histone 
      acetylation.
PG  - 229-236
LID - S0378-4274(18)31471-1 [pii]
LID - 10.1016/j.toxlet.2018.06.1221 [doi]
AB  - Our previous in vivo studies showed that prenatal caffeine exposure (PCE) could 
      restrain the development of chondrogenesis, which may delay fetal articular 
      cartilage development and increase susceptibility to osteoarthritis in adults. 
      So, the goal of the current study is to clarify theincreasing susceptibility to 
      adult osteoarthritis in caffeine-exposed female offspring and its'mechanism. 
      Pregnant rats were treated with 120 mg/kg.d caffeine or equal volumes of saline 
      from gestational day (GD) 9 to 20. knee joints were collected from GD20 female 
      fetuses and 18-week old female offspring which was treated with strenuous running 
      for 6 weeks (55 min/day at 20 m/min) load to induce osteoarthritis. Knee joints 
      from GD20 fetuses and adult offspring were collected for histochemistry and 
      immunohistochemistry. Next, chondrocytes were isolated from 1-day-old newborn 
      rats and in vitro studies were conducted where the cells in primary culture were 
      exposed to 1, 10, and 100 muM caffeine and 250, 500, and 1,250 nM corticosterone. 
      Insulin-like growth factor 1 (IGF-1) signal pathway genes' expression levels in 
      fetal chondrocytes were studied, and IGF-1 histone acetylation was detected in 
      vitro. Immunohistochemical results showed low expression levels of IGF-1 
      signaling genes (IGF-1, IRS-1, AKT, and COL2A1) both in fetal and adult cartilage 
      with PCE. For adult offspring, histological results and Mankin score revealed 
      increased cartilage destruction and accelerated osteoarthritis progression in PCE 
      group with strenuous running exercise. Analysis in vitro revealed that caffeine 
      and corticosterone impeded the expression of IGF-1 signaling pathway aggrecan and 
      COL2A1 genes, but only corticosterone decreased H3K9 and H3K27 acetylation in the 
      IGF-1 promoter region. In concluson, PCE low functional programmed cartilage 
      IGF-1 by histone acetylation modification via overexposure to corticosterone and 
      delayed articular cartilage development from fetus to adults. Then, the delayed 
      cartilage development increased susceptibility to osteoarthritis in offsprings.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Tan, Yang
AU  - Tan Y
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China.
FAU - Lu, Kaihang
AU  - Lu K
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China.
FAU - Li, Jing
AU  - Li J
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China.
FAU - Ni, Qubo
AU  - Ni Q
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China.
FAU - Zhao, Zhe
AU  - Zhao Z
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China.
FAU - Magdalou, Jacques
AU  - Magdalou J
AD  - UMR 7561 CNRS-Universitede Lorraine, Faculte de Medicine, Vandoeuvre-les-Nancy, 
      France.
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
DEP - 20180630
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Aggrecans)
RN  - 0 (COL2A1 protein, rat)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Collagen Type II)
RN  - 0 (Histones)
RN  - 0 (insulin-like growth factor-1, rat)
RN  - 3G6A5W338E (Caffeine)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Acetylation
MH  - Aggrecans/genetics/metabolism
MH  - Animals
MH  - Caffeine/*toxicity
MH  - Cartilage, Articular/*drug effects/metabolism/pathology
MH  - Cells, Cultured
MH  - Central Nervous System Stimulants/*toxicity
MH  - Chondrocytes/drug effects/metabolism/pathology
MH  - Chondrogenesis/*drug effects
MH  - Collagen Type II/genetics/metabolism
MH  - Corticosterone/toxicity
MH  - Disease Progression
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Gestational Age
MH  - Histones/*metabolism
MH  - Insulin-Like Growth Factor I/genetics/*metabolism
MH  - Male
MH  - Maternal Exposure/adverse effects
MH  - Osteoarthritis/*chemically induced/genetics/metabolism/pathology
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats, Wistar
MH  - Risk Assessment
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - caffeine
OT  - glucocorticoid
OT  - insulin-like growth factor 1
OT  - intrauterine programming
OT  - osteoarthritis
EDAT- 2018/07/04 06:00
MHDA- 2018/08/30 06:00
CRDT- 2018/07/04 06:00
PHST- 2017/12/08 00:00 [received]
PHST- 2018/05/30 00:00 [revised]
PHST- 2018/06/27 00:00 [accepted]
PHST- 2018/07/04 06:00 [pubmed]
PHST- 2018/08/30 06:00 [medline]
PHST- 2018/07/04 06:00 [entrez]
AID - S0378-4274(18)31471-1 [pii]
AID - 10.1016/j.toxlet.2018.06.1221 [doi]
PST - ppublish
SO  - Toxicol Lett. 2018 Oct 1;295:229-236. doi: 10.1016/j.toxlet.2018.06.1221. Epub 
      2018 Jun 30.