PMID- 31874197 OWN - NLM STAT- MEDLINE DCOM- 20200127 LR - 20200127 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 321 DP - 2020 Mar 15 TI - Subchondral bone dysplasia mediates susceptibility to osteoarthritis in female adult offspring rats induced by prenatal caffeine exposure. PG - 122-130 LID - S0378-4274(19)30420-5 [pii] LID - 10.1016/j.toxlet.2019.12.026 [doi] AB - Our previous studies confirmed that prenatal caffeine exposure (PCE) could induce susceptibility to osteoarthritis in adult offspring rats due to poor chondrocyte differentiation, but its mechanism remains to be further investigated. This study aimed to explore whether subchondral bone dysplasia mediates susceptibility to osteoarthritis in adult offspring rats induced by PCE. Pregnant Wistar rats were treated with caffeine (120 mg/kg.d) or saline from gestational day (GD) 9 to 20. The female offspring were euthanized to collect femurs at GD20, postnatal week (PW) 6, and PW28 (non-ovariectomy and ovariectomy groups) to detect osteoarthritis-like phenotype, subchondral bone mass, ossification center development, and other evidence. The results showed that PCE increased the Mankin score of pathological articular cartilage, but decreased articular cartilage thickness and subchondral bone mass, which were more obvious after ovariectomy. Meanwhile, the correlation analysis results demonstrated that the Mankin score of articular cartilage was significantly negatively correlated with subchondral bone mass, and the thickness of articular cartilage was significantly positively correlated with subchondral bone mass. Further, the length and area of the primary and secondary ossification centers, the number of osteoblasts, and the related genes' expression of osteogenic differentiation (e.g., Runx2, BSP, ALP, and OCN) were all significantly decreased in the PCE group before and after birth. Taken together, PCE induced susceptibility to osteoarthritis in adult female offspring, which was likely related to the subchondral bone dysplasia and reduction of subchondral bone mass production due to developmental disorder of primary and secondary ossification centers caused by osteoblast differentiation disability before and after birth. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Xie, Xingkui AU - Xie X AD - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China. 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 - Xiao, Hao AU - Xiao H AD - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. FAU - Wen, Yinxian AU - Wen 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 - 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, Wuhan University School of Basic Medical Sciences, 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 - 20191223 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Central Nervous System Stimulants) RN - 3G6A5W338E (Caffeine) SB - IM MH - Age Factors MH - Animals MH - Bone Diseases, Developmental/*chemically induced/genetics/metabolism/pathology MH - Caffeine/*toxicity MH - Cartilage, Articular/*drug effects/pathology MH - Cell Differentiation/drug effects MH - Central Nervous System Stimulants/*toxicity MH - Female MH - Femur/drug effects/metabolism/pathology MH - Gestational Age MH - Osteoarthritis/*chemically induced/genetics/metabolism/pathology MH - Osteoblasts/drug effects/metabolism/pathology MH - Osteogenesis/*drug effects/genetics MH - Ovariectomy MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Rats, Wistar MH - Sex Factors MH - Tibia/drug effects/metabolism/pathology OTO - NOTNLM OT - Caffeine OT - Dysplasia OT - Osteoarthritis OT - Subchondral bone EDAT- 2019/12/25 06:00 MHDA- 2020/01/28 06:00 CRDT- 2019/12/25 06:00 PHST- 2019/10/18 00:00 [received] PHST- 2019/12/17 00:00 [revised] PHST- 2019/12/18 00:00 [accepted] PHST- 2019/12/25 06:00 [pubmed] PHST- 2020/01/28 06:00 [medline] PHST- 2019/12/25 06:00 [entrez] AID - S0378-4274(19)30420-5 [pii] AID - 10.1016/j.toxlet.2019.12.026 [doi] PST - ppublish SO - Toxicol Lett. 2020 Mar 15;321:122-130. doi: 10.1016/j.toxlet.2019.12.026. Epub 2019 Dec 23.