MicroRNA-495 Inhibits New Bone Regeneration via Targeting High Mobility Group AT-Hook 2 (HMGA2)

Abstract

BackgroundMicroRNAs play critical roles in post-translational gene expression. In this study, we explored the role of miR-495 in new bone regeneration.Material/MethodsMurine calvarial osteoblasts were isolated and cultured. Microarray was performed to identify differential miRNAs in medicarpin-induced osteoblasts differentiation. Luciferase reporter assay was performed to identify the target gene of miRNA. Murine osteoblast cells were transfected with miC, miR-495, or anti-miR-495. CCK-8 and flow cytometry were performed to detect osteoblasts proliferation and apoptosis. Western blot was used to analyze apoptosis-related proteins. qRT-PCR analysis was performed to detect gene expression. ALP activity and mineralized nodule formation test were used to evaluate bone formation. Dill-hole injury model was constructed and micro CT was utilized to measuring bone healing.ResultsMicroarray analysis identified miR-495 as our miRNA of interest and luciferase reporter assay identified HMGA2 as its target gene. Over-expression of miR-495 significantly inhibited ALP activity and mineralized nodule formation as well as the expression of RUNX-2, BMP-2, and Osterix. Also, miR-495 over-expression inhibited osteoblasts proliferation and promoted apoptosis obviously. In this in vivo study, the downregulation of miR-495 promoted murine femur healing.ConclusionsMiR-495 inhibits new bone regeneration via targeting high mobility group AT-Hook 2 (HMGA2). We propose that targeting miR-495 may be a promising therapeutic approach for bone regeneration.

MicroRNA‑98‑5p prevents bone regeneration by targeting high mobility group AT‑Hook 2

“…The effect of miR-98-5p on the osteogenic differentiation of the mouse preosteoblast cell line, MC3T3-E1, was subsequently investigated in the current study. Consistent with previous studies (27,29), the results of the present study demonstrated that miR-98-5p significantly inhibited MC3T3-E1 cell osteogenic differentiation by repressing the expression of HMGA2. In addition, miR-98-5p upregulation significantly inhibited cell viability and induced apoptosis in MC3T3-E1 cells and these effects were eliminated by HMGA2 overexpression.…”

“…Wei et al (28) demonstrated that miR let-7 promoted MSC osteogenesis in vitro and in vivo by inhibiting HMGA2 expression (28). It has also been demonstrated that miR-495 prevents new bone regeneration by targeting HMGA2 (29). However, the association between miR-98-5p and HMGA2 has not yet been elucidated.…”

Identification of the Genetic Basis for the Large-tailed Phenotypic Trait in Han Sheep Through Integrated mRNA and miRNA Analysis of Tail Fat Tissue Samples

“…Formosa et al (2014) further found that miR-154, miR-376a, miR-376c, miR-381, and miR-495 controlled metastatic prostate regulate cancer cells proliferation, apoptosis, migration, and invasion [69]. Additional research has identi ed miR-495 as an inhibitor of bone regeneration, gastric cancer cell migration, and invasion, potentially owing to its ability to target high-mobility group AT-Hook 2 [70,71]. We identi ed oar-miR-150, oar-miR-30a-3p, oar-miR-543-3p, oar-miR-412-3p, and oar-miR-154a-3p as DEMs in the present study, suggesting that they may be important regulators of metabolic activity and tail fat deposition in sheep.…”

Therapeutic potential of microRNAs in osteoporosis function by regulating the biology of cells related to bone homeostasis

“…A report has showed that miR-495 overexpression promoted murine calvarial OB apoptosis and inhibited proliferation obviously via targeting the high-mobility group, AT-Hook 2 (HMGA2), in their study (Z. Tian, Zhou, Xu, & Bai, 2017 mRNA. Overexpression of miR-182 in OB lineage cells not only inhibited osteoblastic differentiation and proliferation, but also increased cell apoptosis, and FoxO1 was identified as the target of miR-182 (K. M. Kim et al, 2012).…”