Skip to main content
Top
Published in: International Orthopaedics 5/2015

01-05-2015 | Original Paper

Differential expression of long noncoding ribonucleic acids during osteogenic differentiation of human bone marrow mesenchymal stem cells

Authors: Liang Wang, Yipeng Wang, Zhengyao Li, Ziquan Li, Bin Yu

Published in: International Orthopaedics | Issue 5/2015

Login to get access

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.
Literature
1.
go back to reference 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 16:735–749CrossRefPubMed 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 16:735–749CrossRefPubMed
2.
go back to reference 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 2:67–80CrossRefPubMedCentralPubMed 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 2:67–80CrossRefPubMedCentralPubMed
3.
go back to reference 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 372:2023–2030CrossRefPubMed 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 372:2023–2030CrossRefPubMed
4.
go back to reference Pecina M, Vukicevic S (2014) Tissue engineering and regenerative orthopaedics (TERO). Int Orthop 38:1757–1760CrossRefPubMed Pecina M, Vukicevic S (2014) Tissue engineering and regenerative orthopaedics (TERO). Int Orthop 38:1757–1760CrossRefPubMed
5.
go back to reference 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 2:107–111CrossRefPubMedCentralPubMed 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 2:107–111CrossRefPubMedCentralPubMed
6.
go back to reference 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 32:925–931CrossRefPubMed 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 32:925–931CrossRefPubMed
8.
go back to reference Lee JT, Bartolomei MS (2013) X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 152:1308–1323CrossRefPubMed Lee JT, Bartolomei MS (2013) X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 152:1308–1323CrossRefPubMed
9.
go back to reference 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 477:295–300CrossRefPubMedCentralPubMed 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 477:295–300CrossRefPubMedCentralPubMed
10.
go back to reference Li X, Wu Z, Fu X, Han W (2013) Long noncoding RNAs: insights from biological features and functions to diseases. Med Res Rev 33:517–553CrossRefPubMed Li X, Wu Z, Fu X, Han W (2013) Long noncoding RNAs: insights from biological features and functions to diseases. Med Res Rev 33:517–553CrossRefPubMed
12.
go back to reference Heino TJ, Hentunen TA (2008) Differentiation of osteoblasts and osteocytes from mesenchymal stem cells. Curr Stem Cell Res Ther 3:131–145CrossRefPubMed Heino TJ, Hentunen TA (2008) Differentiation of osteoblasts and osteocytes from mesenchymal stem cells. Curr Stem Cell Res Ther 3:131–145CrossRefPubMed
13.
go back to reference Gomez-Barrena E, Sola CA, Bunu CP (2014) Regulatory authorities and orthopaedic clinical trials on expanded mesenchymal stem cells. Int Orthop 38:1803–1809CrossRefPubMed Gomez-Barrena E, Sola CA, Bunu CP (2014) Regulatory authorities and orthopaedic clinical trials on expanded mesenchymal stem cells. Int Orthop 38:1803–1809CrossRefPubMed
14.
go back to reference Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641CrossRefPubMed Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641CrossRefPubMed
15.
go back to reference Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159CrossRefPubMed Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159CrossRefPubMed
16.
go back to reference 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 329:689–693CrossRefPubMedCentralPubMed 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 329:689–693CrossRefPubMedCentralPubMed
17.
go back to reference 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 287:21926–21935CrossRefPubMedCentralPubMed 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 287:21926–21935CrossRefPubMedCentralPubMed
18.
go back to reference 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 7:124CrossRefPubMedCentralPubMed 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 7:124CrossRefPubMedCentralPubMed
20.
go back to reference 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 36:1354–1369CrossRefPubMedCentralPubMed 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 36:1354–1369CrossRefPubMedCentralPubMed
21.
go back to reference Vimalraj S, Selvamurugan N (2012) MicroRNAs: synthesis, gene regulation and osteoblast differentiation. Curr Issues Mol Biol 15:7–18PubMed Vimalraj S, Selvamurugan N (2012) MicroRNAs: synthesis, gene regulation and osteoblast differentiation. Curr Issues Mol Biol 15:7–18PubMed
23.
go back to reference 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 16:324–337CrossRef 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 16:324–337CrossRef
24.
go back to reference 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 42:1113–1117CrossRefPubMedCentralPubMed 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 42:1113–1117CrossRefPubMedCentralPubMed
25.
go back to reference 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 25:69–80CrossRefPubMed 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 25:69–80CrossRefPubMed
Metadata
Title
Differential expression of long noncoding ribonucleic acids during osteogenic differentiation of human bone marrow mesenchymal stem cells
Authors
Liang Wang
Yipeng Wang
Zhengyao Li
Ziquan Li
Bin Yu
Publication date
01-05-2015
Publisher
Springer Berlin Heidelberg
Published in
International Orthopaedics / Issue 5/2015
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-015-2683-0

Other articles of this Issue 5/2015

International Orthopaedics 5/2015 Go to the issue