The Role of lncRNAs in Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

Author(s): Jicheng Wang, Shizhang Liu, Jiyuan Shi, Huitong Liu, Jingyuan Li, Song Zhao, Zhi Yi*.

Journal Name: Current Stem Cell Research & Therapy

Volume 15 , Issue 3 , 2020

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Abstract:

Bone Marrow Mesenchymal Stem Cells (BMSCs) are one of the primary cells found in the bone marrow, and they can differentiate into osteoblasts, chondrocytes, adipocytes and even myoblasts, and are, therefore, considered pluripotent cells. Because of their multipotential differentiation, selfrenewal capability, immunomodulation and other potential activities, BMSCs have become an important source of seed cells for gene therapy, tissue engineering, cell replacement therapy and regenerative medicine. Long non-coding RNA (lncRNA) is an RNA molecule greater than 200 nucleotides in length that is expressed in a variety of species, including animals, plants, yeast, prokaryotes, and viruses, but lacks an apparent open reading frame, and does not have the function of translation into proteins. Many studies have shown that lncRNAs play an important role in the osteogenic differentiation of BMSCs. Here, we describe the role of lncRNAs in the osteogenic differentiation of BMSCs, in order to provide a new theoretical and experimental basis for bone tissue engineering and clinical treatment.

Keywords: Bone marrow mesenchymal stem cells (BMSCs), long noncoding RNAs (lncRNAs), osteogenic differentiation, bone defects, bone regeneration, bone tissue engineering, treatment.

[1]
Friedenstein AJ, Chailakhyan RK, Gerasimov UV. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet 1987; 20(3): 263-72.
[http://dx.doi.org/10.1111/j.1365-2184.1987.tb01309.x] [PMID: 3690622]
[2]
Sun L, Goff LA, Trapnell C, et al. Long noncoding RNAs regulate adipogenesis. Proc Natl Acad Sci USA 2013; 110(9): 3387-92.
[http://dx.doi.org/10.1073/pnas.1222643110] [PMID: 23401553]
[3]
Mattick JS, Makunin IV. Non-coding RNA. Hum Mol Genet 2006; 15(Spec No 1): R17-29.
[http://dx.doi.org/10.1093/hmg/ddl046] [PMID: 16651366]
[4]
Elling R, Chan J, Fitzgerald KA. Emerging role of long noncoding RNAs as regulators of innate immune cell development and inflammatory gene expression. Eur J Immunol 2016; 46(3): 504-12.
[http://dx.doi.org/10.1002/eji.201444558] [PMID: 26820238]
[5]
Lander ES, Linton LM, Birren B, et al. International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 2001; 409(6822): 860-921.
[http://dx.doi.org/10.1038/35057062] [PMID: 11237011]
[6]
Costa FF. Non-coding RNAs: new players in eukaryotic biology. Gene 2005; 357(2): 83-94.
[http://dx.doi.org/10.1016/j.gene.2005.06.019] [PMID: 16111837]
[7]
Sosińska P, Mikuła-Pietrasik J, Książek K. The double-edged sword of long non-coding RNA: The role of human brain-specific BC200 RNA in translational control, neurodegenerative diseases, and cancer. Mutat Res Rev Mutat Res 2015; 766: 58-67.
[http://dx.doi.org/10.1016/j.mrrev.2015.08.002] [PMID: 26596549]
[8]
Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol 2014; 32(5): 453-61.
[http://dx.doi.org/10.1038/nbt.2890] [PMID: 24811520]
[9]
Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 2013; 495(7441): 333-8.
[http://dx.doi.org/10.1038/nature11928] [PMID: 23446348]
[10]
Ma L, Bajic VB, Zhang Z. On the classification of long non-coding RNAs. RNA Biol 2013; 10(6): 925-33.
[http://dx.doi.org/10.4161/rna.24604] [PMID: 23696037]
[11]
Guo X, Gao L, Liao Q, et al. Long non-coding RNAs function annotation: a global prediction method based on bi-colored networks. Nucleic Acids Res 2013; 41(2)e35
[http://dx.doi.org/10.1093/nar/gks967] [PMID: 23132350]
[12]
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet 2009; 10(3): 155-9.
[http://dx.doi.org/10.1038/nrg2521] [PMID: 19188922]
[13]
Fitzgerald KA, Caffrey DR. Long noncoding RNAs in innate and adaptive immunity. Curr Opin Immunol 2014; 26: 140-6.
[http://dx.doi.org/10.1016/j.coi.2013.12.001] [PMID: 24556411]
[14]
Yang Q, Jia L, Li X, et al. Long Noncoding RNAs: New Players in the Osteogenic Differentiation of Bone Marrow- and Adipose-Derived Mesenchymal Stem Cells. Stem Cell Rev Rep 2018; 14(3): 297-308.
[http://dx.doi.org/10.1007/s12015-018-9801-5] [PMID: 29464508]
[15]
Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem 2012; 81: 145-66.
[http://dx.doi.org/10.1146/annurev-biochem-051410-092902] [PMID: 22663078]
[16]
Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell 2013; 154(1): 26-46.
[http://dx.doi.org/10.1016/j.cell.2013.06.020] [PMID: 23827673]
[17]
Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes Dev 2006; 20(11): 1470-84.
[http://dx.doi.org/10.1101/gad.1416106] [PMID: 16705037]
[18]
Ohno M, Fukagawa T, Lee JS, Ikemura T. Triplex-forming DNAs in the human interphase nucleus visualized in situ by polypurine/polypyrimidine DNA probes and antitriplex antibodies. Chromosoma 2002; 111(3): 201-13.
[http://dx.doi.org/10.1007/s00412-002-0198-0] [PMID: 12355210]
[19]
Smart F, Aschrafi A, Atkins A, et al. Two isoforms of the cold-inducible mRNA-binding protein RBM3 localize to dendrites and promote translation. J Neurochem 2007; 101(5): 1367-79.
[http://dx.doi.org/10.1111/j.1471-4159.2007.04521.x] [PMID: 17403028]
[20]
Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010; 11(9): 597-610.
[http://dx.doi.org/10.1038/nrg2843] [PMID: 20661255]
[21]
Paraskevopoulou MD, Hatzigeorgiou AG. Analyzing MiRNA-LncRNA interactions. Methods Mol Biol 2016; 1402: 271-86.
[http://dx.doi.org/10.1007/978-1-4939-3378-5_21] [PMID: 26721498]
[22]
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell 2009; 136(4): 629-41.
[http://dx.doi.org/10.1016/j.cell.2009.02.006] [PMID: 19239885]
[23]
Zhang W, Dong R, Diao S, Du J, Fan Z, Wang F. Differential long noncoding RNA/mRNA expression profiling and functional network analysis during osteogenic differentiation of human bone marrow mesenchymal stem cells. Stem Cell Res Ther 2017; 8(1): 30.
[http://dx.doi.org/10.1186/s13287-017-0485-6] [PMID: 28173844]
[24]
Wang Q, Yang Q, Chen G, et al. LncRNA expression profiling of BMSCs in osteonecrosis of the femoral head associated with increased adipogenic and decreased osteogenic differentiation. Sci Rep 2018; 8(1): 9127.
[http://dx.doi.org/10.1038/s41598-018-27501-2] [PMID: 29904151]
[25]
Zhou Q, Tang X, Tian X, et al. LncRNA MALAT1 negatively regulates MDSCs in patients with lung cancer. J Cancer 2018; 9(14): 2436-42.
[http://dx.doi.org/10.7150/jca.24796] [PMID: 30026840]
[26]
Zheng S, Wang YB, Yang YL, et al. LncRNA MALAT1 inhibits osteogenic differentiation of mesenchymal stem cells in osteoporosis rats through MAPK signaling pathway. Eur Rev Med Pharmacol Sci 2019; 23(11): 4609-17.
[PMID: 31210287]
[27]
Wang Q, Li Q, Zhou P, et al. Upregulation of the long non-coding RNA SNHG1 predicts poor prognosis, promotes cell proliferation and invasion, and reduces apoptosis in glioma. Biomed Pharmacother 2017; 91: 906-11.
[http://dx.doi.org/10.1016/j.biopha.2017.05.014] [PMID: 28501778]
[28]
Deng R, Zhang J, Chen J. lncRNA SNHG1 negatively regulates miRNA‑101‑3p to enhance the expression of ROCK1 and promote cell proliferation, migration and invasion in osteosarcoma. Int J Mol Med 2019; 43(3): 1157-66.
[PMID: 30592267]
[29]
Zhu W, He X, Hua Y, Li Q, Wang J, Gan X. The E3 ubiquitin ligase WWP2 facilitates RUNX2 protein transactivation in a mono-ubiquitination manner during osteogenic differentiation. J Biol Chem 2017; 292(27): 11178-88.
[http://dx.doi.org/10.1074/jbc.M116.772277] [PMID: 28500134]
[30]
Kumar Y, Kapoor I, Khan K, et al. E3 Ubiquitin Ligase Fbw7 Negatively Regulates Osteoblast Differentiation by Targeting Runx2 for Degradation. J Biol Chem 2015; 290(52): 30975-87.
[http://dx.doi.org/10.1074/jbc.M115.669531] [PMID: 26542806]
[31]
Jiang Y, Wu W, Jiao G, Chen Y, Liu H. LncRNA SNHG1 modulates p38 MAPK pathway through Nedd4 and thus inhibits osteogenic differentiation of bone marrow mesenchymal stem cells. Life Sci 2019; 228: 208-14.
[http://dx.doi.org/10.1016/j.lfs.2019.05.002] [PMID: 31055087]
[32]
Yang L, Li Y, Gong R, et al. The long non-coding RNA-ORLNC1 regulates bone mass by directing mesenchymal stem cell fate. Mol Ther 2019; 27(2): 394-410.
[http://dx.doi.org/10.1016/j.ymthe.2018.11.019] [PMID: 30638773]
[33]
Pawar K, Hanisch C, Palma Vera SE, Einspanier R, Sharbati S. Down regulated lncRNA MEG3 eliminates mycobacteria in macrophages via autophagy. Sci Rep 2016; 6: 19416.
[http://dx.doi.org/10.1038/srep19416] [PMID: 26757825]
[34]
Lehner B, Kunz P, Saehr H, Fellenberg J. Epigenetic silencing of genes and microRNAs within the imprinted Dlk1-Dio3 region at human chromosome 14.32 in giant cell tumor of bone. BMC Cancer 2014; 14: 495.
[http://dx.doi.org/10.1186/1471-2407-14-495] [PMID: 25005035]
[35]
Zhuang W, Ge X, Yang S, et al. Upregulation of lncRNA MEG3 promotes osteogenic differentiation of mesenchymal stem cells from multiple myeloma patients by targeting BMP4 transcription. Stem Cells 2015; 33(6): 1985-97.
[http://dx.doi.org/10.1002/stem.1989] [PMID: 25753650]
[36]
Wang Q, Li Y, Zhang Y, et al. LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p. Biomed Pharmacother 2017; 89: 1178-86.
[http://dx.doi.org/10.1016/j.biopha.2017.02.090] [PMID: 28320084]
[37]
Chen S, Jia L, Zhang S, Zheng Y, Zhou Y. DEPTOR regulates osteogenic differentiation via inhibiting MEG3-mediated activation of BMP4 signaling and is involved in osteoporosis. Stem Cell Res Ther 2018; 9(1): 185.
[http://dx.doi.org/10.1186/s13287-018-0935-9] [PMID: 29973283]
[38]
Rinn JL, Kertesz M, Wang JK, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 2007; 129(7): 1311-23.
[http://dx.doi.org/10.1016/j.cell.2007.05.022] [PMID: 17604720]
[39]
Wan Y, Chang HY. HOTAIR: Flight of noncoding RNAs in cancer metastasis. Cell Cycle 2010; 9(17): 3391-2.
[http://dx.doi.org/10.4161/cc.9.17.13122] [PMID: 20864820]
[40]
Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 2012; 9(6): 703-19.
[http://dx.doi.org/10.4161/rna.20481] [PMID: 22664915]
[41]
Shen JJ, Zhang CH, Chen ZW, et al. LncRNA HOTAIR inhibited osteogenic differentiation of BMSCs by regulating Wnt/β-catenin pathway. Eur Rev Med Pharmacol Sci 2019; 23(17): 7232-46.
[PMID: 31539110]
[42]
Balint E, Lapointe D, Drissi H, et al. Phenotype discovery by gene expression profiling: mapping of biological processes linked to BMP-2-mediated osteoblast differentiation. J Cell Biochem 2003; 89(2): 401-26.
[http://dx.doi.org/10.1002/jcb.10515] [PMID: 12704803]
[43]
Stopa M, Benes V, Ansorge W, Gressner AM, Dooley S. Genomic locus and promoter region of rat Smad7, an important antagonist of TGFbeta signaling. Mamm Genome 2000; 11(2): 169-76.
[http://dx.doi.org/10.1007/s003350010032] [PMID: 10656934]
[44]
Wang A, Ding X, Sheng S, Yao Z. Bone morphogenetic protein receptor in the osteogenic differentiation of rat bone marrow stromal cells. Yonsei Med J 2010; 51(5): 740-5.
[http://dx.doi.org/10.3349/ymj.2010.51.5.740] [PMID: 20635450]
[45]
Li D, Yu K, Xiao T, et al. LOC103691336/miR-138-5p/BMPR2 axis modulates Mg-mediated osteogenic differentiation in rat femoral fracture model and rat primary bone marrow stromal cells. J Cell Physiol 2019; 234(11): 21316-30.
[http://dx.doi.org/10.1002/jcp.28736] [PMID: 31081160]
[46]
Kanduri C. Kcnq1ot1: a chromatin regulatory RNA. Semin Cell Dev Biol 2011; 22(4): 343-50.
[http://dx.doi.org/10.1016/j.semcdb.2011.02.020] [PMID: 21345374]
[47]
Chen B, Ma J, Li C, Wang Y. Long noncoding RNA KCNQ1OT1 promotes proliferation and epithelial‑mesenchymal transition by regulation of SMAD4 expression in lens epithelial cells. Mol Med Rep 2018; 18(1): 16-24.
[http://dx.doi.org/10.3892/mmr.2018.8987] [PMID: 29749509]
[48]
Li C, Miao R, Zhang J, Qu K, Liu C. Long non-coding RNA KCNQ1OT1 mediates the growth of hepatocellular carcinoma by functioning as a competing endogenous RNA of miR-504. Int J Oncol 2018.
[http://dx.doi.org/10.3892/ijo.2018.4313] [PMID: 29532864]
[49]
Gao X, Ge J, Li W, Zhou W, Xu L. LncRNA KCNQ1OT1 promotes osteogenic differentiation to relieve osteolysis via Wnt/β-catenin activation. Cell Biosci 2018; 8: 19.
[http://dx.doi.org/10.1186/s13578-018-0216-4] [PMID: 29541443]
[50]
Wang CG, Liao Z, Xiao H, et al. LncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214. Exp Mol Pathol 2019; 107: 77-84.
[http://dx.doi.org/10.1016/j.yexmp.2019.01.012] [PMID: 30703347]
[51]
Dewing AS, Rueli RH, Robles MJ, et al. Expression and regulation of mouse selenoprotein P transcript variants differing in non-coding RNA. RNA Biol 2012; 9(11): 1361-9.
[http://dx.doi.org/10.4161/rna.22290] [PMID: 23064117]
[52]
Steinbrenner H, Speckmann B, Klotz LO. Selenoproteins: Antioxidant selenoenzymes and beyond. Arch Biochem Biophys 2016; 595: 113-9.
[http://dx.doi.org/10.1016/j.abb.2015.06.024] [PMID: 27095226]
[53]
Sun X, Yuan Y, Xiao Y, et al. Long non-coding RNA, Bmcob, regulates osteoblastic differentiation of bone marrow mesenchymal stem cells. Biochem Biophys Res Commun 2018; 506(3): 536-42.
[http://dx.doi.org/10.1016/j.bbrc.2018.09.142] [PMID: 30361096]
[54]
Hong JH, Hwang ES, McManus MT, et al. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 2005; 309(5737): 1074-8.
[http://dx.doi.org/10.1126/science.1110955] [PMID: 16099986]
[55]
Byun MR, Hwang JH, Kim AR, et al. Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation. Cell Death Differ 2014; 21(6): 854-63.
[http://dx.doi.org/10.1038/cdd.2014.8] [PMID: 24510127]
[56]
Xiao Z, Baudry J, Cao L, et al. Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit adipogenesis. J Clin Invest 2018; 128(1): 157-74.
[http://dx.doi.org/10.1172/JCI93725] [PMID: 29202470]
[57]
Matsumoto Y, La Rose J, Kent OA, et al. Reciprocal stabilization of ABL and TAZ regulates osteoblastogenesis through transcription factor RUNX2. J Clin Invest 2016; 126(12): 4482-96.
[http://dx.doi.org/10.1172/JCI87802] [PMID: 27797343]
[58]
Li CJ, Xiao Y, Yang M, et al. Long noncoding RNA Bmncr regulates mesenchymal stem cell fate during skeletal aging. J Clin Invest 2018; 128(12): 5251-66.
[http://dx.doi.org/10.1172/JCI99044] [PMID: 30352426]
[59]
Shang G, Wang Y, Xu Y, et al. Long non-coding RNA TCONS_00041960 enhances osteogenesis and inhibits adipogenesis of rat bone marrow mesenchymal stem cell by targeting miR-204-5p and miR-125a-3p. J Cell Physiol 2018; 233(8): 6041-51.
[http://dx.doi.org/10.1002/jcp.26424] [PMID: 29319166]
[60]
Liang WC, Fu WM, Wang YB, et al. H19 activates Wnt signaling and promotes osteoblast differentiation by functioning as a competing endogenous RNA. Sci Rep 2016; 6: 20121.
[http://dx.doi.org/10.1038/srep20121] [PMID: 26853553]
[61]
Hu J, Liao H, Ma Z, et al. Focal adhesion kinase signaling mediated the enhancement of osteogenesis of human mesenchymal stem cells induced by extracorporeal shockwave. Sci Rep 2016; 6: 20875.
[http://dx.doi.org/10.1038/srep20875] [PMID: 26863924]
[62]
Wu J, Zhao J, Sun L, Pan Y, Wang H, Zhang WB. Long non-coding RNA H19 mediates mechanical tension-induced osteogenesis of bone marrow mesenchymal stem cells via FAK by sponging miR-138. Bone 2018; 108: 62-70.
[http://dx.doi.org/10.1016/j.bone.2017.12.013] [PMID: 29253550]
[63]
Sun Y, Wang P, Yang W, Shan Y, Zhang Q, Wu H. The role of lncRNA MSC-AS1/miR-29b-3p axis-mediated CDK14 modulation in pancreatic cancer proliferation and Gemcitabine-induced apoptosis. Cancer Biol Ther 2019; 20(6): 729-39.
[http://dx.doi.org/10.1080/15384047.2018.1529121] [PMID: 30915884]
[64]
Zhang N, Hu X, He S, et al. LncRNA MSC-AS1 promotes osteogenic differentiation and alleviates osteoporosis through sponging microRNA-140-5p to upregulate BMP2. Biochem Biophys Res Commun 2019; 519(4): 790-6.
[http://dx.doi.org/10.1016/j.bbrc.2019.09.058] [PMID: 31551149]
[65]
Xu S, Wang P, You Z, et al. The long non-coding RNA EPB41L4A-AS2 inhibits tumor proliferation and is associated with favorable prognoses in breast cancer and other solid tumors. Oncotarget 2016; 7(15): 20704-17.
[http://dx.doi.org/10.18632/oncotarget.8007] [PMID: 26980733]
[66]
Ota T, Suzuki Y, Nishikawa T, et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet 2004; 36(1): 40-5.
[http://dx.doi.org/10.1038/ng1285] [PMID: 14702039]
[67]
Shan Y, Ma J, Pan Y, Hu J, Liu B, Jia L. LncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1. Cell Death Dis 2018; 9(7): 722.
[http://dx.doi.org/10.1038/s41419-018-0759-7] [PMID: 29915311]
[68]
Chi R, Chen X, Liu M, et al. Role of SNHG7-miR-653-5p-STAT2 feedback loop in regulating neuroblastoma progression. J Cell Physiol 2019; 234(8): 13403-12.
[http://dx.doi.org/10.1002/jcp.28017] [PMID: 30623419]
[69]
Cui P, Zhao X, Liu J, et al. miR-146a interacting with lncRNA EPB41L4A-AS1 and lncRNA SNHG7 inhibits proliferation of bone marrow-derived mesenchymal stem cells. J Cell Physiol 2019; 1-17.
[http://dx.doi.org/10.1002/jcp.29217] [PMID: 31612476]


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VOLUME: 15
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Year: 2020
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