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.
Highlights
Diabetes mellitus (DM) affected 158.8 million people aged 20–79 years in the Western Pacific region in 2017, translating to a 9.5% prevalence rate [1]
To understand the expression of these genes in the human body more intuitively, we constructed human tissue–enriched protein expression maps using the data from the Genotype-Tissue Expression (GTEX) database, which contains bone marrow data from autopsy specimens obtained from subjects who were healthy before death
We found no miRNA dataset related directly to diabetic bone disease; considering the close relationship between skeletal muscle and bone, and the large size and good quality of the GSE25462 dataset, we used these data in this study (Supplementary Figure 2A– 2D)
Summary
Diabetes mellitus (DM) affected 158.8 million people aged 20–79 years in the Western Pacific region in 2017, translating to a 9.5% prevalence rate [1]. [9] In a rat model of type 2 diabetes mellitus (T2DM), insufficient differentiation of MSCs into osteoblasts led to inflammation that impaired fracture healing, and metformin promoted this differentiation [10, 11]. Stearoyl–coenzyme A desaturase-1 (SCD1) can inhibit the development of diabetic bone disease by promoting osteogenesis. 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. Findings: SCD1 expression in bone marrow was downregulated in patients with T2DM and low-energy fracture, and SCD1 expression promotes BM-MSC osteogenic differentiation. Interpretation: The regulation of BM-MSCs by SCD1 is a necessary condition for osteogenesis through the miR203a/FOS and miR-1908/EXO1 regulatory pathways
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