Long noncoding RNA H19 mediates LCoR to impact the osteogenic and adipogenic differentiation of mBMSCs in mice through sponging miR‐188

Abstract

The research aimed to examine the expression of lncRNA H19, miR-188, and LCoR in mouse bone marrow stromal stem cells (mBMSCs), and to investigate the regulatory mechanism of lncRNA H19/miR-188/LCoR in osteogenic and adipogenic differentiation of mBMSCs. The expression of miR-188 in mBMSCs and osteogenesis induced mBMSCs was detected by stem-loop RT-PCR, while the expression of H19 and LCoR in mBMSCs and adipogenesis induced mBMSCs was examined by qRT-PCR. Luciferase reporter assay verified the targeted relationship between miR-188 and H19 or LCoR. Cell proliferation ability was determined by MTT assay, while cell surface markers of mBMSCs were analyzed via flow cytometry. Alkaline phosphatase staining and Alizarin red staining was utilized to detect the osteogenic differentiation capability of mBMSCs, whereas Oil red O staining was applied to examine the ability of adipogenic differentiation of mBMSCs. The expression of miR-188 was lower in osteogenesis induced mBMSCs compared with normal mBMSCs, while H19 and LCoR were downregulated in adipogenic induced mBMSCs. Si-H19 could significantly increase the mRNA level of miR-188. Meanwhile, miR-188 directly regulated LCoR in mBMSCs. Overexpression of miR-188 and knockdown of LCoR suppressed osteogenic differentiation and induced adipogenic differentiation in mBMSCs. Long noncoding RNA H19 mediates LCoR to regulate the balance between osteogenic and adipogenic differentiation of mBMSCs in mice through sponging miR-188.

Long non‐coding RNA (lncRNA) H19 induces hepatic steatosis through activating MLXIPL and mTORC1 networks in hepatocytes

“…Subconfluent mouse hepatocyte iHPx cells were infected with Ad-H19, Ad-siH19, Ad-siMlxipl, Ad-H19 + Ad-siMlxip or Ad-RFP for 36 h. The infected hepatocytes were collected and subcutaneously injected into the flanks of athymic nude mice for 10 d. Masses at the injection sites were retrieved, fixed and snap-frozen or paraffin embedded. 52,53 Furthermore, H19 was shown to promote skeletal muscle insulin sensitivity by targeting AMPK. B, Frozen sections were subjected to ORO staining.…”

Role of LncRNAs and CircRNAs in Bone Metabolism and Osteoporosis

“…In malignant tumors, it is well known that H19 is aberrantly expressed and regulates cell proliferation, migration, invasions, antiapoptosis, etc., as well as acts as a microRNA sponge to indirectly regulate the expression of microRNA target genes (Ye et al, 2019). Wang et al (2018a) have described that the lncRNA H19 and Liganddependent co-repressor (LCoR) were upregulated in mBMSCs under osteogenic induction, and miR-188 was downregulated, which regulated LCoR in mBMSCs. Subsequent investigation has elucidated that, when H19 was silenced, the levels of miR-188 were increased, leading to reduced osteogenic differentiation in mBMSCs (Wang et al, 2018a).…”

GROWTH AND DEVELOPMENT SYMPOSIUM: STEM AND PROGENITOR CELLS IN ANIMAL GROWTH: Long noncoding RNAs in adipogenesis and adipose development of meat animals12

“…LncRNA binds to mRNA and inhibits its translation. (Huang et al, 2016;Wang et al, 2018) HoxA-AS3 (Xu et al, 2010;Liu et al, 2014aLiu et al, , 2014b (Zhang et al, 2018) 1 ADSCs = adipose-derived stem cells; BMSCs = bone-marrow derived mesenchymal stem cells; SVs = stromal vascular cells; C/EBPα = CCAAT/enhancer-binding protein alpha; HDAC = histone deacetylase; LCoR = ligand-dependent corepressor; ceRNA = competing endogenous RNA; EZH2 = enhancer of zeste 2; H3K27me3 = H3 lysine-27 trimethylation; Runx2 = runt-related transcription factor 2; FABP4 = fatty acid binding protein 4; GILZ = glucocorticoid-induced leucine zipper; CTGF = connective tissue growth factor; PTEN = phosphatase and tensin homolog; PPARγ = peroxisome proliferatoractivated receptor gamma; hnRNPU = heterogeneous nuclear ribonucleoprotein U; SIRT1 = Sirtuin 1; AdipoQ = adiponectin; RBM14 = RNA binding motif protein 14. Table 1.…”

“…The differentiation of MSC is regulated by intricate signaling pathways and epigenetic events, determining the specific lineage and phenotype (Augello and De Bari, 2010). Recent studies revealed that lncRNA ADINR (Xiao et al, 2015), HoxA-AS3 (Zhu et al, 2016), MIR31HG (Huang et al, 2017b), TINCR (Liu et al, 2018d), and Plnc1 (Zhu et al, 2018) favor adipogenic commitment, whereas H19 (Huang et al, 2016;Wang et al, 2018), MEG3 (Li et al, 2017), TCONS_00041960 (Shang et al, 2018), and GAS5 (Li et al, 2018;Liu et al, 2018a) suppress adipocyte determination, playing key roles in the determining molecular switch between adipocyte and other mesenchymal cell types.…”

“…Mechanistically, H19-derived miR-675 directly targets histone deacetylases (HDACs, essential molecules in adipogenesis) 4, 5, and 6 and then downregulates their expression, resulting in reduced adipogenesis (Huang et al, 2016). In mouse BMSCs, H19 sponges miR-188 to enhance the expression of ligand-dependent corepressor (LCoR, a negative regulator of adipogenesis), regulating the balance between osteogenic and adipogenic differentiation of BMSCs (Wang et al, 2018).…”