MicroRNA-23a-5p regulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting mitogen-activated protein kinase-13

Ren, Gang; Sun, Jing; Li, Meng‐Meng; Zhang, Yongdong; Li, Rong‑Hua; Li, Yuming

doi:10.3892/mmr.2018.8452

Cited by 13 publications

(13 citation statements)

References 25 publications

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“…For example, the expression of miR-23a-5p was upregulated in the differentiation of BMSCs into osteoblasts. It regulates the downstream mitogen-activated protein kinase-13, thus promoting differentiation of osteoblasts (Ren et al 2018 ). MiR-30a-5p can regulate the differentiation of cells (Franzetti et al 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA HCG18 inhibits the differentiation of human bone marrow-derived mesenchymal stem cells in osteoporosis by targeting miR-30a-5p/NOTCH1 axis

Che

Gong

Zhao

et al. 2020

Mol Med

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Background Recent studies have demonstrated that long non-coding RNAs (LncRNAs) can influence bone cell differentiation and formation. However, it is unclear whether lncRNA HCG18 is involved in osteoporosis (OP). This study was conducted to investigate the regulation of HCG18 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Methods BMSCs were isolated and cultured from mouse pathological models and osteoporosis patients. RT-qPCR was performed to detect the expression of HCG18 and miR-30a-5p in BMSCs. The interaction between HCG18 and miR-30a-5p was analyzed by dual luciferase assay and RNA pulldown assay. The interaction between miR-30a-5p and NOTCH1 3′-UTR was analyzed by dual luciferase assay. RT-qPCR and Western blotting were used to detect the expression of osteogenic genes Runx2, OCN and OPN. Hindlimb-unloaded (HU) mice model was established, and HCG18 was knocked down on bone-formation surfaces by using lentivirus mediated shRNA transfection. Results The expression of HCG18 was increased in BMSCs of OP patients, while the expression of miR-30a-5p was decreased. The expression of HCG18 and miR-30a-5p was negatively correlated in BMSCs. During the differentiation from BMSCs to osteoblasts, the expression of HCG18 was significantly downregulated, and the expression of miR-30a-5p was significantly upregulated. Overexpression of HCG18 was able to reverse the osteogenic-induced upregulation of miR-30a-5p expression, and knockdown of HCG18 further promoted the expression of miR-30a-5p. In addition, miR-30a-5p partially abolished the effect of HCG18 on osteogenic differentiation of BMSCs. NOTCH1 was a target protein of miR-30a-5p, and upregulation of NOTCH1 reversed the effect of miR-30a-5p on osteogenic differentiation of BMSCs. Furthermore, this study found that lentivirus mediated HCG18 knockdown on the bone-formation surfaces of hindlimb-unloaded (HU) mice partially alleviated unloading-induced bone loss Conclusions HCG18 inhibited osteogenic differentiation of BMSCs induced by OP via the miR-30a-5p/NOTCH1 axis. HCG18 can be identified as a regulator of osteogenic differentiation of BMSCs.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA HCG18 inhibits the differentiation of human bone marrow-derived mesenchymal stem cells in osteoporosis by targeting miR-30a-5p/NOTCH1 axis

Che

Gong

Zhao

et al. 2020

Mol Med

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“…However, the effect of LINc00707 on the osteogenic differentiation of HBMScs is yet to be fully elucidated. miRNAs are endogenous non-coding small single-stranded RNAs (13,14), and are involved in the regulation of osteogenic differentiation of HBMScs (15)(16)(17). For instance, miR-33a-5p has been shown to regulate osteogenic differentiation by targeting SATB homeobox 2 expression in HBMScs (18).…”

Section: Downregulation Of Linc00707 Promotes Osteogenic Differentiatmentioning

confidence: 99%

Downregulation of LINC00707 promotes osteogenic differentiation of human bone marrow‑derived mesenchymal stem cells by regulating DKK1 via targeting miR‑103a‑3p

Feng

et al. 2020

Int J Mol Med

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Human bone marrow-derived mesenchymal stem cells (HBMScs) have the potential of multidirectional differentiation and self-renewal, which is important for the formation of human bone. It has been reported that long non-coding RNAs (lncRNAs) serve important roles in HBMSc osteogenic differentiation. The current study aimed to investigate the roles of long intergenic non-protein coding RNA 00707 (LINc00707) and microRNA (miR)-103a-3p in the osteogenic differentiation of HBMScs. Reverse transcription-quantitative PcR (RT-qPcR) was performed to detect the expression levels of LINc00707, miR-103a-3p and osteogenesis-related genes (Alkaline phosphatase, osteocalcin, osteopontin and RUNX family transcription factor 2) in HBMScs cultured in proliferation medium (PM) and osteogenic medium (OM). Mineralized matrix deposition was measured using Alizarin Red S staining. The protein expression levels of osteogenesis-related genes were detected by western blotting. The relationships between LINc00707, miR-103a-3p and dickkopf WNT signaling pathway inhibitor 1 (dKK1) were predicted using Starbase and TargetScan7.2, and were further assessed with a dual-luciferase reporter assay. After 21 days of cell culture, the results indicated that expression of LINc00707 was downregulated, and those of miR-103a-3p and osteogenesis-related genes were upregulated in OM-cultured HBMScs. However, there was no significant difference in the aforementioned gene expression levels in PM-cultured HBMScs. Small interfering (si)LINc00707 increased the deposition of mineralized matrix and promoted the expression levels of osteogenesis-related proteins. Furthermore, miR-103a-3p was predicted to be a target gene of LINc00707, its expression was significantly upregulated by siLINC00707, while overexpression of miR-103a-3p increased the expression levels of osteogenesis-related proteins. dKK1 was also predicted to be a target gene of miR-103a-3p and could inhibit the expression levels of osteogenesis-related proteins, but such effect of dKK1 could be reversed by the miR-103a-3p mimic. In conclusion, the present results suggested that LINc00707 regulated dKK1 expression by targeting miR-103a-3p to regulate osteogenic differentiation.

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“…Many miRNAs inhibited the osteogenic differentiation of cells in various ways. For example, miR-383 (Tang et al, 2018) directly regulated Satb2, miR-27a (Gong et al, 2016) reduced the protein and gene expression level of Sp7, miR-10b (Yang et al, 2017) overexpression up-regulated the expression of signal transducer and activator of transcription 1 (STAT1) and blocked the nuclear translocation of Runx2, miR-23a-5p (Ren et al, 2018;Yang et al, 2020) directly targeted and inhibited the expression of Runx2 and MAPK13, miR-206 suppressed the glutamine metabolism (Chen et al, 2019), miR-320a negatively regulated homeobox a10 (HOXA10), miR-214 (Guo et al, 2017) participates in the inhibition of the c-jun n-terminal kinase (JNK) and p38 pathways, miR-495 (Tian et al, 2017) directly targeted the high-mobility group A2 gene (HMGA2), miR-125a-3p negatively regulated G-protein-coupled receptor kinase interacting protein-1 (GIT1) (Tu et al, 2016), and after miR-223 (Zhang et al, 2018) and miR-23a cluster (Godfrey et al, 2018) inhibition, short-chain dehydrogenase/reductase 3 (DHRS3) and HoxA cluster were respectively targeted to promote osteogenic differentiation.…”

Section: Mirnas Regulate Other Factors In Osteoblastsmentioning

confidence: 99%

Roles of MicroRNAs in Bone Destruction of Rheumatoid Arthritis

Zhao

2020

Front. Cell Dev. Biol.

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As an important pathological result of rheumatoid arthritis (RA), bone destruction will lead to joint injury and dysfunction. The imbalance of bone metabolism caused by increased osteoclast activities and decreased osteoblast activities is the main cause of bone destruction in RA. MicroRNAs (MiRNAs) play an important role in regulating bone metabolic network. Recent studies have shown that miRNAs play indispensable roles in the occurrence and development of bone-related diseases including RA. In this paper, the role of miRNAs in regulating bone destruction of RA in recent years, especially the differentiation and activities of osteoclast and osteoblast, is reviewed. Our results will not only help provide ideas for further studies on miRNAs' roles in regulating bone destruction, but give candidate targets for miRNAs-based drugs research in bone destruction therapy of RA as well.

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MicroRNA-23a-5p regulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting mitogen-activated protein kinase-13

Cited by 13 publications

References 25 publications

Long noncoding RNA HCG18 inhibits the differentiation of human bone marrow-derived mesenchymal stem cells in osteoporosis by targeting miR-30a-5p/NOTCH1 axis

Long noncoding RNA HCG18 inhibits the differentiation of human bone marrow-derived mesenchymal stem cells in osteoporosis by targeting miR-30a-5p/NOTCH1 axis

Downregulation of LINC00707 promotes osteogenic differentiation of human bone marrow‑derived mesenchymal stem cells by regulating DKK1 via targeting miR‑103a‑3p

Roles of MicroRNAs in Bone Destruction of Rheumatoid Arthritis

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