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Long non-coding RNA H19 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by regulating microRNA-140-5p/SATB2 axis

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Abstract

The osteogenic differentiation of mesenchymal stem cells (MSCs) has potential clinical values in the treatment of bone-related diseases. Long non-coding RNA H19 and microRNA-140-5p (miR-140-5p) have attracted much attention of researchers by virtue of their biological importance in cell differentiation and bone formation. Moreover, bioinformatics analyses suggest that miR-140-5p have the potential to bind with H19 and SATB homeobox 2 (SATB2). In this study, we further explored whether H19 could regulate osteogenic differentiation of human bone marrow-derived MSCs (BM-MSCs) by miR-140-5p/SATB2 axis. RT-qPCR assay was conducted to examine the expression of H19, miR-140-5p and SATB2. The osteogenic differentiation capacity of BM-MSCs was assessed through alkaline phosphatase (ALP) activity and osteogenic marker expression. The relationships among H19, miR-140-5p and SATB2 were examined through bioinformatics analyses, luciferase reporter assay, RIP assay and RNA pull-down assay. H19 expression was remarkably increased and miR-140-5p expression was dramatically reduced during osteogenic differentiation of BM-MSCs. Functional analyses revealed that H19 overexpression or miR-140-5p depletion accelerated osteogenic differentiation of BM-MSCs. Conversely, H19 loss or miR-140-5p increase suppressed osteogenic differentiation of BM-MSCs. MiR-140-5p was confirmed as a target of H19, and miR-140-5p could bind to SATB2 as well. Moreover, H19 knockdown reduced SATB2 expression by upregulating miR-140-5p. Additionally, miR-140-5p depletion antagonized the inhibitory effect of H19 knockdown on osteogenic differentiation of BM-MSCs. And, miR-140-5p inhibited osteogenic differentiation of BM-MSCs by targeting SATB2. In conclusion, H19 promoted osteogenic differentiation of BM-MSCs through regulating miR-140-5p/SATB2 axis, deepening our understanding on the molecular mechanisms of H19 in coordinating osteogenesis.

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References

  • Bak RO and Mikkelsen JG 2014 miRNA sponges: soaking up miRNAs for regulation of gene expression. Wiley Interdiscip. Rev. RNA 5 317–333

    CAS  PubMed  Google Scholar 

  • Baker N, Boyette LB and Tuan RS 2015 Characterization of bone marrow-derived mesenchymal stem cells in aging. Bone 70 37–47

    CAS  PubMed  Google Scholar 

  • Baum R and Gravallese EM 2016 Bone as a target organ in rheumatic disease: impact on osteoclasts and osteoblasts. Clin. Rev. Allergy Immunol. 51 1–15

    PubMed  PubMed Central  Google Scholar 

  • Beermann J, Piccoli MT, Viereck J and Thum T 2016 Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol. Rev. 96 1297–1325

    CAS  PubMed  Google Scholar 

  • Ciuffreda MC, Malpasso G, Musaro P, Turco V and Gnecchi M 2016 Protocols for in vitro differentiation of human mesenchymal stem cells into osteogenic, chondrogenic and adipogenic lineages. Methods Mol. Biol. 1416 149–158

    CAS  PubMed  Google Scholar 

  • Clark EA, Kalomoiris S, Nolta JA and Fierro FA 2014 Concise review: MicroRNA function in multipotent mesenchymal stromal cells. Stem Cells 32 1074–1082

    CAS  PubMed  Google Scholar 

  • Dacic S, Kalajzic I, Visnjic D, Lichtler A and Rowe D 2001 Col1a1-driven transgenic markers of osteoblast lineage progression. J. Bone Mineral Res. 16 1228–1236

    CAS  Google Scholar 

  • Feng L, Shi L, Lu YF, Wang B, Tang T, Fu WM, He W, Li G, et al. 2018 Linc-ROR Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Functioning as a Competing Endogenous RNA for miR-138 and miR-145. Mol. Ther. Nucleic Acids 11 345–353

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fitzsimmons REB and Mazurek MS 2018 Mesenchymal stromal/stem cells in regenerative medicine and tissue engineering. Stem Cells Int. 2018 8031718

    PubMed  PubMed Central  Google Scholar 

  • Franceschi RT and Xiao G 2003 Regulation of the osteoblast-specific transcription factor, Runx2: Responsiveness to multiple signal transduction pathways. J. Cell. Biochem. 88 446–454

    CAS  PubMed  Google Scholar 

  • Gong Y, Qian Y, Yang F, Wang H and Yu Y 2014 Lentiviral-mediated expression of SATB2 promotes osteogenic differentiation of bone marrow stromal cells in vitro and in vivo. Eur. J. Oral Sci. 122 190–197

    CAS  PubMed  Google Scholar 

  • Green D, Dalmay T and Fraser WD 2015 Role of miR-140 in embryonic bone development and cancer. Clin. Sci. 129 863–873

    CAS  Google Scholar 

  • Hagenhoff A, Bruns CJ, Zhao Y, von Luttichau I, Niess H, Spitzweg C and Nelson PJ 2016 Harnessing mesenchymal stem cell homing as an anticancer therapy. Expert Opin. Biol. Ther. 16 1079–1092

    CAS  PubMed  Google Scholar 

  • Huang C, Geng J and Jiang S 2017 MicroRNAs in regulation of osteogenic differentiation of mesenchymal stem cells. Cell Tissue Res. 368 229–238

    CAS  PubMed  Google Scholar 

  • Huang Y, Zheng Y, Jia L and Li W 2015 Long Noncoding RNA H19 Promotes osteoblast differentiation via TGF-β1/Smad3/HDAC signaling pathway by deriving miR-675. Stem Cells 33 3481–3492

    CAS  PubMed  Google Scholar 

  • Huo S, Zhou Y, He X, Wan M, Du W, Xu X, Ye L, Zhou X, et al. 2018 Insight into the role of long non-coding RNAs during osteogenesis in mesenchymal stem cells. Curr. Stem Cell Res. Ther. 13 52–59

    CAS  PubMed  Google Scholar 

  • Hwang S, Park S-K, Lee HY, Kim SW, Lee JS, Choi EK, You D, Kim C-S, et al. 2014 miR-140-5p suppresses BMP2-mediated osteogenesis in undifferentiated human mesenchymal stem cells. FEBS Lett. 588 2957–2963

    CAS  PubMed  Google Scholar 

  • Kallen AN, Zhou X-B, Xu J, Qiao C, Ma J, Yan L, Lu L, Liu C, et al. 2013 The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol. Cell 52 101–112

    CAS  PubMed  Google Scholar 

  • Komori T 2016 Cell death in chondrocytes, osteoblasts, and osteocytes. Int. J. Mol. Sci. 17 2045

    PubMed Central  Google Scholar 

  • Kucuksayan H and Akca H 2017 The crosstalk between p38 and Akt signaling pathways orchestrates EMT by regulating SATB2 expression in NSCLC cells. Tumour Biol. 39 1010428317706212

    PubMed  Google Scholar 

  • Lee WC, Guntur AR, Long F and Rosen CJ 2017 Energy metabolism of the osteoblast: implications for osteoporosis. Endocr. Rev. 38 255–266

    PubMed  PubMed Central  Google Scholar 

  • Li Z, Jin C, Chen S, Zheng Y, Huang Y, Jia L, Ge W and Zhou Y 2017 Long non-coding RNA MEG3 inhibits adipogenesis and promotes osteogenesis of human adipose-derived mesenchymal stem cells via miR-140-5p. Mol. Cell Biochem. 433 51–60

    CAS  PubMed  Google Scholar 

  • Liang W-C, Fu W-M, Wang Y-B, Sun Y-X, Xu L-L, Wong C-W, Chan K-M, Li G, et al. 2016 H19 activates Wnt signaling and promotes osteoblast differentiation by functioning as a competing endogenous RNA. Sci. Re. 6 20121

    CAS  Google Scholar 

  • Liu Y, Li G and Zhang JF 2017 The role of long non-coding RNA H19 in musculoskeletal system: A new player in an old game. Exp. Cell Res. 360 61–65

    CAS  PubMed  Google Scholar 

  • Long F 2011 Building strong bones: molecular regulation of the osteoblast lineage. Nat. Rev. Mol. Cell Biol .13 27–38

    PubMed  Google Scholar 

  • Luo Y, Fang Z, Ling Y and Luo W 2019 LncRNA-H19 acts as a ceRNA to regulate HE4 expression by sponging miR-140 in human umbilical vein endothelial cells under hyperglycemia with or without alpha-Mangostin. Biomed. Pharmacother. 118 109256

    CAS  PubMed  Google Scholar 

  • Marom R, Shur I, Solomon R and Benayahu D 2005 Characterization of adhesion and differentiation markers of osteogenic marrow stromal cells. J. Cell. Physiol. 202 41–48

    CAS  PubMed  Google Scholar 

  • Maruotti N, Corrado A and Cantatore FP 2017 Osteoblast role in osteoarthritis pathogenesis. J. Cell Physiol. 232 2957–2963

    CAS  PubMed  PubMed Central  Google Scholar 

  • Phatak P and Donahue JM 2017 Biotinylated micro-RNA pull down assay for identifying miRNA targets. Bio-protocol 7 e2253

    Google Scholar 

  • Polymeri A, Giannobile WV and Kaigler D 2016 Bone marrow stromal stem cells in tissue engineering and regenerative medicine. Horm. Metab. Res. 48 700–713

    CAS  PubMed  Google Scholar 

  • Raveh E, Matouk IJ, Gilon M and Hochberg A 2015 The H19 Long non-coding RNA in cancer initiation, progression and metastasis - a proposed unifying theory. Mol. Cancer 14 184

    PubMed  PubMed Central  Google Scholar 

  • Sarukhan A, Zanotti L and Viola A 2015 Mesenchymal stem cells: myths and reality. Swiss Med. Wkly. 145 w14229

    PubMed  Google Scholar 

  • Thomson DW and Dinger ME 2016 Endogenous microRNA sponges: evidence and controversy. Nat. Rev. Genet. 17 272–283

    CAS  PubMed  Google Scholar 

  • Tye CE, Gordon JA, Martin-Buley LA, Stein JL, Lian JB and Stein GS 2015 Could lncRNAs be the missing links in control of mesenchymal stem cell differentiation? J. Cell Physiol. 230 526–534

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang L, Wang Y, Li Z, Li Z and Yu B 2015 Differential expression of long noncoding ribonucleic acids during osteogenic differentiation of human bone marrow mesenchymal stem cells. Int. Orthopaedics 39 1013–1019

    Google Scholar 

  • Wang Q, Li Y, Zhang Y, Ma L, Lin L, Meng J, Jiang L, Wang L, et al. 2017 LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p. Biomed. Pharmacother. 89 1178–1186

    CAS  PubMed  Google Scholar 

  • Wu J, Zhao J, Sun L, Pan Y, Wang H and Zhang W-B 2018 Long non-coding RNA H19 mediates mechanical tension-induced osteogenesis of bone marrow mesenchymal stem cells via FAK by sponging miR-138. Bone 108 62–70

    CAS  PubMed  Google Scholar 

  • Wang Y, Wang L and Sui M 2018 Long non-coding RNA H19 promotes proliferation of Hodgkin’s lymphoma via AKT pathway. J. Buon. 23 1825–1831

    PubMed  Google Scholar 

  • Wang X, Cheng Z, Dai L, Jiang T, Jia L, Jing X, An L, Wang H and Liu M 2019 Knockdown of long noncoding RNA H19 represses the progress of pulmonary fibrosis through the transforming growth factor beta/Smad3 pathway by regulating microRNA 140. Mol. Cell Biol. 39. https://doi.org/10.1128/MCB.00143-19

  • Xie X, Liu M and Meng Q 2019 Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone Joint Res. 8 323–332

    PubMed  PubMed Central  Google Scholar 

  • Xu J, Xia Y, Zhang H, Guo H, Feng K and Zhang C 2018 Overexpression of long non-coding RNA H19 promotes invasion and autophagy via the PI3K/AKT/mTOR pathways in trophoblast cells. Biomed. Pharmacother. 101 691–697

    CAS  PubMed  Google Scholar 

  • Zhang J, Tu Q, Grosschedl R, Kim MS, Griffin T, Drissi H, Yang P and Chen J 2011 Roles of SATB2 in osteogenic differentiation and bone regeneration. Tissue Eng. A 17 1767–1776

    CAS  Google Scholar 

  • Zhao X, Qu Z, Tickner J, Xu J, Dai K and Zhang X 2014 The role of SATB2 in skeletogenesis and human disease. Cytokine Growth Factor Rev. 25 35–44

    CAS  PubMed  Google Scholar 

  • Zhen L, Jiang X, Chen Y and Fan D 2017 MiR-31 is involved in the high glucose-suppressed osteogenic differentiation of human periodontal ligament stem cells by targeting Satb2. Am. J. Transl. Res. 9 2384–2393

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao H, Peng R, Liu Q, Liu D, Du P, Yuan J, Peng G and Liao Y 2016 The lncRNA H19 interacts with miR-140 to modulate glioma growth by targeting iASPP. Arch. Biochem. Biophys. 610 1–7

    CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Natural Science Fund of Science and Technology Development Project, Science and Technology Agency of Jilin Province (Grant No. 20160101002JC).

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Authors and Affiliations

  1. Department of Orthopedics, WuWei People’s Hospital, Wuwei, China

    Hu Bi & Dong Wang

  2. Department of Oncology Surgery, WuWei People’s Hospital, Wuwei, China

    Xiaoyu Liu

  3. Department of Orthopedics, The Third Hospital of Jilin University, China-Japan Union Hospital, Changchun, China

    Gang Wang

  4. Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Xuejian Wu

Authors
  1. Hu Bi
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  2. Dong Wang
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  3. Xiaoyu Liu
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  4. Gang Wang
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  5. Xuejian Wu
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Corresponding authors

Correspondence to Gang Wang or Xuejian Wu.

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Communicated by Ullas Kolthur-Seetharam.

Communicated by Ullas Kolthur-Seetharam

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Bi, H., Wang, D., Liu, X. et al. Long non-coding RNA H19 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by regulating microRNA-140-5p/SATB2 axis. J Biosci 45, 56 (2020). https://doi.org/10.1007/s12038-020-0024-y

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