PMID- 32454462 OWN - NLM STAT- MEDLINE DCOM- 20210219 LR - 20210219 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 12 IP - 10 DP - 2020 May 26 TI - MiR-1908/EXO1 and MiR-203a/FOS, regulated by scd1, are associated with fracture risk and bone health in postmenopausal diabetic women. PG - 9549-9584 LID - 10.18632/aging.103227 [doi] AB - 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. FAU - Chen, Yi-Sheng AU - Chen YS AD - Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China. FAU - Kang, Xue-Ran AU - Kang XR AD - 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. FAU - Zhou, Zi-Hui AU - Zhou ZH AD - Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China. FAU - Yang, Jiang AU - Yang J AD - Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China. FAU - Xin, Qi AU - Xin Q AD - Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China. FAU - Ying, Chen-Ting AU - Ying CT AD - Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China. FAU - Zhang, Yun-Peng AU - Zhang YP AD - Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China. FAU - Tao, Jie AU - Tao J AD - Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200526 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (CDKN1A protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p21) RN - 0 (FOS protein, human) RN - 0 (Genetic Markers) RN - 0 (MIRN1908 microRNA, human) RN - 0 (MIRN203 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Proto-Oncogene Proteins c-fos) RN - EC 1.14.19.1 (SCD1 protein, human) RN - EC 1.14.19.1 (Stearoyl-CoA Desaturase) RN - EC 3.1.- (EXO1 protein, human) RN - EC 3.1.- (Exodeoxyribonucleases) RN - EC 6.5.1.- (DNA Repair Enzymes) SB - IM MH - Cyclin-Dependent Kinase Inhibitor p21/metabolism MH - DNA Repair Enzymes/metabolism MH - Diabetes Mellitus, Type 2/*genetics MH - Down-Regulation/genetics MH - Exodeoxyribonucleases/metabolism MH - Female MH - Fractures, Bone/*genetics MH - Genetic Markers/genetics MH - Humans MH - Mesenchymal Stem Cells/metabolism MH - MicroRNAs/*metabolism MH - Nomograms MH - Postmenopause/*genetics MH - Proto-Oncogene Proteins c-fos/metabolism MH - Risk Assessment/methods MH - Risk Factors MH - Stearoyl-CoA Desaturase/*metabolism PMC - PMC7288911 OTO - NOTNLM OT - bone mesenchymal stem cell (BMSC) OT - diabetes OT - fracture risk OT - nomogram OT - stearoyl-coenzyme A desaturase (SCD1) COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest. EDAT- 2020/05/27 06:00 MHDA- 2021/02/20 06:00 PMCR- 2020/05/31 CRDT- 2020/05/27 06:00 PHST- 2019/09/03 00:00 [received] PHST- 2020/04/13 00:00 [accepted] PHST- 2020/05/27 06:00 [pubmed] PHST- 2021/02/20 06:00 [medline] PHST- 2020/05/27 06:00 [entrez] PHST- 2020/05/31 00:00 [pmc-release] AID - 103227 [pii] AID - 10.18632/aging.103227 [doi] PST - ppublish SO - Aging (Albany NY). 2020 May 26;12(10):9549-9584. doi: 10.18632/aging.103227. Epub 2020 May 26.