Abstract
Purpose
The purpose of this study was to investigate the differential expression and putative function of long noncoding RNAs (lncRNAs) during the osteogenic differentiation of human bone marrow mesenchymal stem cells (MSCs).
Methods
The differential lncRNAs expression profiles of undifferentiated and differentiated cells during osteogenic differentiation were established by lncRNA microarray. Microarray data were validated using quantitative reverse transcription–polymerase chain reaction (qRT-PCR). Bioinformatic analyses (gene ontology, pathway and co-expression network analysis) were applied for further study of these differentially expressed lncRNAs.
Results
A total of 1,206 differentially expressed lncRNAs were identified during the process of osteogenic differentiation. Among these lncRNAs, 687 were up-regulated and 519 were down-regulated more than two-fold. Bioinformatic analyses were applied for further study of these differentially expressed lncRNAs. Further analysis found 48 regulated enhancer-like lncRNA and 14 lincRNA. The dynamic expression trends H19 and uc022axw.1 were then observed using qRT-PCR. The results showed that the two up-regulated lncRNAs are likely to play important roles in osteogenic differentiation process.
Conclusions
Taken together, our study first revealed the expression profiles of lncRNAs in osteogenic differentiation of human bone marrow MSCs. It provides an experimental basis for further research on lncRNAs functions during osteogenic differentiation of human bone marrow MSCs.
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References
Frith JE, Thomson B, Genever PG (2010) Dynamic three-dimensional culture methods enhance mesenchymal stem cell properties and increase therapeutic potential. Tissue Eng Part C Methods 16:735–749
Rastegar F, Shenaq D, Huang J, Zhang W, Zhang BQ, He BC, Chen L, Zuo GW, Luo Q, Shi Q, Wagner ER, Huang E, Gao Y, Gao JL, Kim SH, Zhou JZ, Bi Y, Su Y, Zhu G, Luo J, Luo X, Qin J, Reid RR, Luu HH, Haydon RC, Deng ZL, He TC (2010) Mesenchymal stem cells: Molecular characteristics and clinical applications. World J Stem Cells 2:67–80
Macchiarini P, Jungebluth P, Go T, Asnaghi MA, Rees LE, Cogan TA, Dodson A, Martorell J, Bellini S, Parnigotto PP, Dickinson SC, Hollander AP, Mantero S, Conconi MT, Birchall MA (2008) Clinical transplantation of a tissue-engineered airway. Lancet 372:2023–2030
Pecina M, Vukicevic S (2014) Tissue engineering and regenerative orthopaedics (TERO). Int Orthop 38:1757–1760
Reinders ME, de Fijter JW, Roelofs H, Bajema IM, de Vries DK, Schaapherder AF, Claas FH, van Miert PP, Roelen DL, van Kooten C, Fibbe WE, Rabelink TJ (2013) Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study. Stem Cells Transl Med 2:107–111
Liu P, Deng Z, Han S, Liu T, Wen N, Lu W, Geng X, Huang S, Jin Y (2008) Tissue-engineered skin containing mesenchymal stem cells improves burn wounds. Artif Organs 32:925–931
Guttman M, Rinn JL (2012) Modular regulatory principles of large non-coding RNAs. Nature 482:339–346
Lee JT, Bartolomei MS (2013) X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 152:1308–1323
Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, Young G, Lucas AB, Ach R, Bruhn L, Yang X, Amit I, Meissner A, Regev A, Rinn JL, Root DE, Lander ES (2011) lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477:295–300
Li X, Wu Z, Fu X, Han W (2013) Long noncoding RNAs: insights from biological features and functions to diseases. Med Res Rev 33:517–553
Bianco P, Robey PG (2001) Stem cells in tissue engineering. Nature 414:118–121
Heino TJ, Hentunen TA (2008) Differentiation of osteoblasts and osteocytes from mesenchymal stem cells. Curr Stem Cell Res Ther 3:131–145
Gomez-Barrena E, Sola CA, Bunu CP (2014) Regulatory authorities and orthopaedic clinical trials on expanded mesenchymal stem cells. Int Orthop 38:1803–1809
Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641
Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159
Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–693
Zhang Y, Xie RL, Gordon J, LeBlanc K, Stein JL, Lian JB, van Wijnen AJ, Stein GS (2012) Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2. J Biol Chem 287:21926–21935
Weber M, Sotoca AM, Kupfer P, Guthke R, van Zoelen EJ (2013) Dynamic modelling of microRNA regulation during mesenchymal stem cell differentiation. BMC Syst Biol 7:124
Gangaraju VK, Lin H (2009) MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol 10:116–125
Goff LA, Boucher S, Ricupero CL, Fenstermacher S, Swerdel M, Chase LG, Adams CC, Chesnut J, Lakshmipathy U, Hart RP (2008) Differentiating human multipotent mesenchymal stromal cells regulate microRNAs: prediction of microRNA regulation by PDGF during osteogenesis. Exp Hematol 36:1354–1369
Vimalraj S, Selvamurugan N (2012) MicroRNAs: synthesis, gene regulation and osteoblast differentiation. Curr Issues Mol Biol 15:7–18
Kung JT, Colognori D, Lee JT (2013) Long noncoding RNAs: past, present, and future. Genetics 193:651–669
Sheik MJ, Gaughwin PM, Lim B, Robson P, Lipovich L (2010) Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA 16:324–337
Loewer S, Cabili MN, Guttman M, Loh YH, Thomas K, Park IH, Garber M, Curran M, Onder T, Agarwal S, Manos PD, Datta S, Lander ES, Schlaeger TM, Daley GQ, Rinn JL (2010) Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet 42:1113–1117
Wang Y, Xu Z, Jiang J, Xu C, Kang J, Xiao L, Wu M, Xiong J, Guo X, Liu H (2013) Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell 25:69–80
Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81372007).
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The authors declare that they have no conflict of interest.
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Wang, L., Wang, Y., Li, Z. et al. Differential expression of long noncoding ribonucleic acids during osteogenic differentiation of human bone marrow mesenchymal stem cells. International Orthopaedics (SICOT) 39, 1013–1019 (2015). https://doi.org/10.1007/s00264-015-2683-0
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DOI: https://doi.org/10.1007/s00264-015-2683-0