Research Paper Volume 12, Issue 10 pp 9549—9584
MiR-1908/EXO1 and MiR-203a/FOS, regulated by scd1, are associated with fracture risk and bone health in postmenopausal diabetic women
- 1 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China
- 2 Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
- 3 Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China
Received: September 3, 2019 Accepted: April 13, 2020 Published: May 26, 2020
https://doi.org/10.18632/aging.103227How to Cite
Copyright © 2020 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Stearoyl–coenzyme A desaturase-1 (SCD1) can inhibit the development of diabetic bone disease by promoting osteogenesis. In this study, we examined whether this regulation by SCD1 is achieved by regulating the expression of related miRNAs.
Methods: SCD1 expression levels were observed in human bone-marrow mesenchymal stem cells (BM-MSCs) of patients with type 2 diabetes mellitus (T2DM), and the effect of SCD1 on osteogenesis was observed in human adipose-derived MSCs transfected with the SCD1 lentiviral system. We designed a bioinformatics prediction model to select important differentially expressed miRNAs, and established protein–protein interaction and miRNA–mRNA networks. miRNAs and mRNAs were extracted and their differential expression was detected. The SCD1–miRNA–mRNA network was validated.
Findings: SCD1 expression in bone marrow was downregulated in patients with T2DM and low-energy fracture, and SCD1 expression promotes BM-MSC osteogenic differentiation. The predictors in the nomogram were seven microRNAs, including hsa-miR-1908 and hsa-miR-203a. SCD1 inhibited the expression of CDKN1A and FOS, but promoted the expression of EXO1 and PLS1. miR-1908 was a regulator of EXO1 expression, and miR-203a was a regulator of FOS expression.
Interpretation: The regulation of BM-MSCs by SCD1 is a necessary condition for osteogenesis through the miR-203a/FOS and miR-1908/EXO1 regulatory pathways.
Abbreviations
ALP: Alkaline phosphatase; BMD: bone mineral density; BM-MSCs: bone marrow–derived mesenchymal stem cells; BPs: biological processes; CCs: cellular components; CDKN1A: cyclin-dependent kinase inhibitor 1A; CIs: confidence intervals; DE-miRNAs: differentially expressed micro-RNAs; DEMs: differentially expressed mRNAs; DM: diabetes mellitus; T2DM: postmenopausal women with; DF: with histories of at least one osteoporotic fracture; EV: empty vector; EXO1: exonuclease 1; FBS: fasting blood-glucose; FOS: c-Fos; GEO: the Gene Expression Omnibus; GO: gene ontology; GTEX: Genotype-Tissue Expression; LASSO: the least absolute shrinkage and selection operator; KEGG: Kyoto Encyclopedia of Genes and Genomes; T2DM: postmenopausal women without, NF with histories of at least one osteoporotic fracture; NC: normal control; T2DM: postmenopausal women without; NM: without histories of at least one osteoporotic fracture; NRF2: the nuclear factor erythroid 2–related factor 2; miRNA: micro-RNA; MFs: molecular functions; mRNAs: expressed messenger RNAs; OA: oleic acid; PLS1: plastin 1; PPI: protein–protein interaction; RT-PCR: Real-time polymerase chain reaction; SCD1: stearoyl–coenzyme A desaturase-1; SCD1-OE: SCD1 overexpression; T2DM: type 2 diabetes mellitus; TCGA: The Cancer Genome Atlas; TNF: tumor necrosis factor; 2HPG: 2h postprandial blood glucose.