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A Core Omnigenic Non-coding Trait Governing Dex-Induced Osteoporotic Effects Identified Without DEXA.
Lu, Li; Cai, Yanzhen; Luo, Xiaoling; Wang, Zhangting; Fung, Sin Hang; Jia, Huanhuan; Yu, Chi Lam; Chan, Wai Yee; Miu, Kai Kei; Xiao, Wende.
Afiliação
  • Lu L; Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, School of Life Science and Biopharmacy, Guangdong Pharmaceutical University, Guangzhou, China.
  • Cai Y; Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, School of Life Science and Biopharmacy, Guangdong Pharmaceutical University, Guangzhou, China.
  • Luo X; Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, School of Life Science and Biopharmacy, Guangdong Pharmaceutical University, Guangzhou, China.
  • Wang Z; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR China.
  • Fung SH; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR China.
  • Jia H; Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, School of Life Science and Biopharmacy, Guangdong Pharmaceutical University, Guangzhou, China.
  • Yu CL; Guangdong Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China.
  • Chan WY; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR China.
  • Miu KK; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR China.
  • Xiao W; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR China.
Front Pharmacol ; 12: 750959, 2021.
Article em En | MEDLINE | ID: mdl-34899306
ABSTRACT
Iatrogenic glucocorticoid (GC)-induced osteoporosis (GIO) is an idiosyncratic form of secondary osteoporosis. Genetic predisposition among individuals may give rise to variant degree of phenotypic changes but there has yet been a documented unified pathway to explain the idiosyncrasy. In this study, we argue that the susceptibility to epigenetic changes governing molecular cross talks along the BMP and PI3K/Akt pathway may underline how genetic background dictate GC-induced bone loss. Concordantly, osteoblasts from BALB/c or C57BL/6 neonatal mice were treated with dexamethasone for transcriptome profiling. Furthermore, we also confirmed that GC-pre-conditioned mesenchymal stem cells (MSCs) would give rise to defective osteogenesis by instigating epigenetic changes which affected the accessibility of enhancer marks. In line with these epigenetic changes, we propose that GC modulates a key regulatory network involving the scavenger receptor Cd36 in osteoblasts pre-conditioning pharmacological idiosyncrasy in GIO.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article