Does DNA Methylation Plays a Critical Role in Osteoblastic Differentiation of Mesenchymal Stem Cells (MSCs)?


Najmaldin Saki 1 , Majid Farshdousti Hagh 2 , * , Esmaeil Mortaz 3 , Abdolreza Ardeshiry Lajimi 4

1 Research Center of Thalassemia and Hemoglobinopathy, Jundishapur University of Medical Sciences, Ahvaz, IR Iran

2 Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, IR Iran

3 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands

4 Young Researchers Club, Science and Research Branch, Islamic Azad University, Tehran, IR Iran

How to Cite: Saki N, Farshdousti Hagh M, Mortaz E, Ardeshiry Lajimi A. Does DNA Methylation Plays a Critical Role in Osteoblastic Differentiation of Mesenchymal Stem Cells (MSCs)?, Iran Red Crescent Med J. 2013 ; 15(8):755-756. doi: 10.5812/ircmj.4615.


Iranian Red Crescent Medical Journal: 15 (8); 755-756
Published Online: August 5, 2013
Article Type: Letter
Received: February 27, 2012
Revised: January 16, 2013
Accepted: June 14, 2013
Copyright © 2013, Iranian Red Crescent Medical Journal. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

Dear Editor,

Mesenchymal stem cells (MSCs) are characterized by ability to differentiate into several cell types and self-renewability. These stem cells have a limited capacity in cell lineage differentiation including osteogenic, adipogenic, chondrogenic, or myogenic lineage differentiations (1). Regarding their ease of isolation and specific characteristics, MSCs have been used widely in regenerative medicine and tissue engineering (2). In spite of identification of several signaling molecules in MSCs differentiation, controlling mechanisms in MSCs differentiation has not well been described. Recently, epigenetic mechanisms have been identified as the master regulatory mechanism in MSCs differentiation such as DNA methylation, histone modification and regulatory micro RNAs (2-4). In this report, we investigate DNA methylation status of ROR2 gene in osteoblastic differentiation of MSCs. We also show that ROR2 promoter was hypomethylated during osteoblastic differentiation for which the details can be found in Noruzinia et al. (5); While other important osteoblastic specific genes did not evaluate. RUNX2 and OSX are two of the most known osteoblast specific transcription factors (6, 7). However, several other non-osteoblast specific transcription factors have been identified to control osteoblast differentiation, including TWIST1 (twist homolog 1), ZBTB16 (zinc finger and BTB domain containing 16), DLX5 and MSX2 (MSH homeobox homolog 2) (8, 9). Therefore, we suggest that those genes (such as RUNX2 and OSX) could be considered as a a subject for future investigations.

Besides, it can be postulated that osteoblastic differentiation of MSCs may be influenced by mechanisms other than DNA methylation (10). Therefore, we suggest that other epigenetic mechanisms including histone modification and regulatory micro RNAs regarded in osteoblastic differentiation of MSCs sould be considered for future studies.




  • 1.

    Saki N, Abroun S, Farshdousti Hagh M, Asgharei F. Neoplastic Bone Marrow Niche: Hematopoietic and Mesenchymal Stem Cells. Cell J. 2011; 13(3) : 131 -6

  • 2.

    Caplan AI. Mesenchymal stem cells and gene therapy. Clin Orthop Relat Res. 2000; (379 Suppl) -70 [PubMed]

  • 3.

    Boquest AC, Noer A, Sorensen AL, Vekterud K, Collas P. CpG methylation profiles of endothelial cell-specific gene promoter regions in adipose tissue stem cells suggest limited differentiation potential toward the endothelial cell lineage. Stem Cells. 2007; 25(4) : 852 -61 [DOI][PubMed]

  • 4.

    Aranda P, Agirre X, Ballestar E, Andreu EJ, Roman-Gomez J, Prieto I, et al. Epigenetic signatures associated with different levels of differentiation potential in human stem cells. PLoS One. 2009; 4(11)[DOI][PubMed]

  • 5.

    Tarfiei G, Noruzinia M, Soleimani M, Kaviani S, Mahmoodinia Maymand M, Farshdousti Hagh M, et al. ROR2 Promoter Methylation Change in Osteoblastic Differentiation of Mesenchymal Stem Cells. Cell J. 2011; 13(1) : 11 -8

  • 6.

    Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002; 108(1) : 17 -29 [PubMed]

  • 7.

    Gollner H, Dani C, Phillips B, Philipsen S, Suske G. Impaired ossification in mice lacking the transcription factor Sp3. Mech Dev. 2001; 106(1-2) : 77 -83 [PubMed]

  • 8.

    Harada S, Rodan GA. Control of osteoblast function and regulation of bone mass. Nature. 2003; 423(6937) : 349 -55 [DOI][PubMed]

  • 9.

    Holleville N, Mateos S, Bontoux M, Bollerot K, Monsoro-Burq AH. Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme. Dev Biol. 2007; 304(2) : 860 -74 [DOI][PubMed]

  • 10.

    Bradley EW, McGee-Lawrence ME, Westendorf JJ. Hdac-mediated control of endochondral and intramembranous ossification. Crit Rev Eukaryot Gene Expr. 2011; 21(2) : 101 -13 [PubMed]