miR‑205 regulates bone turnover in elderly female patients with type 2 diabetes mellitus through targeted inhibition of Runx2

Abstract

The present study aimed to explore the expression of microribonucleic acid (microRNA) (miR)-205 in bone tissues and serum of elderly female patients with type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP), and to investigate the effect of miR-205 on osteogenesis/adipogenesis of bone marrow mesenchymal stem cells (BMSCs) and its mechanism in elderly female mice with T2DM + OP.

Dietary ω-3 Fatty Acid Supplementation Improves Murine Sickle Cell Bone Disease and Reprograms Adipogenesis

“…The OPG/RankL ratio, used to evaluate osteogenesis vs. osteoclastogenesis, was higher in FD SS mice than in the SD SS mouse group ( Figure 3 b, see also Figure S4 ). In FD SS mice exposed to recurrent H/R, the improvement of osteogenesis at the expense of osteoclastogenesis was also supported by the downregulation of miR205, which positively modulates osteoclast activity ( Figure 3 b) [ 32 , 33 , 34 ]. Since matrix-metalloproteinase (MMP-9) plays an important role in the activation of osteoclasts [ 31 , 35 , 36 , 37 ], we evaluated MMP9 expression in bone from FD and SD mouse groups exposed to Rec H/R.…”

“…Since bone homeostasis depends on the balance between osteoclastogenesis/osteoblastogenesis, the finding that FD supplementation increased molecular osteogenic markers, such as Runx2 and Sparc, is particularly interesting and is in agreement with the increased number of osteoprogenitor cells, evaluated by analyzing the CFU-Ob. We also demonstrated downregulation of miR205, which negatively affects osteogenic activity by directly targeting Runx2 [ 32 , 33 , 34 ]. The miR205/Runx2 ratio has been recently proposed as novel marker of bone loss in osteoporosis [ 33 ].…”

“…We also demonstrated downregulation of miR205, which negatively affects osteogenic activity by directly targeting Runx2 [ 32 , 33 , 34 ]. The miR205/Runx2 ratio has been recently proposed as novel marker of bone loss in osteoporosis [ 33 ]. We found, in this study, that the miR205/Rux2 ratio is significantly reduced in Rec H/R FD SS mice when compared to Rec H/R SD SS animals (FD SS 0.56 ± 0.08 vs. SD SS 7.2 ± 0.4, n = 6; p < 0.02), supporting the multimodal action of FD supplementation against SBD.…”

Bioinformatics Analysis of Key Genes and Pathways for Obesity Associated Type 2 Diabetes Mellitus as a Therapeutic Target

“…DEGs in GO terms and pathways might be linked with advancement of obesity associated type 2 diabetes mellitus. ERBB2 [36], DACT1 [37], ARAP1 [38], MYH9 [39], INPPL1 [40], SARM1 [41], NOTCH1 [42], ROBO1 [43], MAPK8IP1 [44], ANK1 [45], SARM1 [46], SREBF2 [47], SIK1 [48], PASK (PAS domain containing serine/threonine kinase) [49], NOS2 [50], OAS3 [51], KL (klotho) [52], PECAM1 [53], S100A12 [54], S100P [55], BATF3 [56], PLEK (pleckstrin) [57], ALOX5 [58], ARG1 [59], CXCL8 [60], CXCR1 [61], PTAFR (platelet activating factor receptor) [62], PYGL (glycogen phosphorylase L) [63], TCF4 [64], CAMP (cathelicidin antimicrobial peptide) [65], RUNX2 [66], PLA2G2A [67], GCG (glucagon) [68], RARRES2 [69] and HAP1 [70] were involved in the genesis of type 2 diabetes mellitus. Recent studies have reported that ACHE (acetylcholinesterase) [71], FGFR3 [72], VLDLR (very low density lipoprotein receptor) [73], SHC1 [74], HDAC6 [75], CHRNA2 [76], CASR (calcium sensing receptor) [77], ELK1 [78], TYK2 [79], CIITA (class II major histocompatibility complex transactivator) [80], ZAP70 [81], GPT (glutamic--pyruvic transaminase) [82], CHI3L1 [83], AIF1 [84], MMP9 [85], ITGB2 [86], CFD (complement factor D) [87], C3AR1 [88], LGALS1 [89], CD14 [90], TIMP1 [91], TLR2 [92], LTF (lactotransferrin) [93], BRCA2 [94] and IGFBP3 [95] promotes the development of obesity.…”

“…IL1R2 [34] and SPINK5 [35] are involved in the development of asthma, but these genes might be associated with development of obesity associated type 2 diabetes mellitus. [52], PECAM1 [53], S100A12 [54], S100P [55], BATF3 [56], PLEK (pleckstrin) [57], ALOX5 [58], ARG1 [59], CXCL8 [60], CXCR1 [61], PTAFR (platelet activating factor receptor) [62], PYGL (glycogen phosphorylase L) [63], TCF4 [64], CAMP (cathelicidin antimicrobial peptide) [65], RUNX2 [66], PLA2G2A [67], GCG (glucagon) [ [87], C3AR1 [88],…”