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Epigenetic modifiers influence lineage commitment of human bone marrow stromal cells: Differential effects of 5-aza-deoxycytidine and trichostatin A
Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, School of Medicine, UK; Medical Biochemistry Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.ORCID iD: 0000-0001-5394-9082
Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, School of Medicine, UK; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, School of Medicine, UK.
2011 (English)In: Differentiation, ISSN 0301-4681, E-ISSN 1432-0436, Vol. 81, no 1, p. 35-41Article in journal (Refereed) Published
Abstract [en]

Clinical imperatives for new bone to replace or restore the function of traumatized or bone lost as a consequence of age or disease has led to the need for therapies or procedures to generate bone for skeletal applications. However, current in vitro methods for the differentiation of human bone marrow stromal cells (HBMSCs) do not, to date, produce homogeneous cell populations of the osteogenic or chondrogenic lineages. As epigenetic modifiers are known to influence differentiation, we investigated the effects of the DNA demethylating agent 5-aza-2′-deoxycytidine (5-aza-dC) or the histone deacetylase inhibitor trichostatin A (TSA) on osteogenic and chondrogenic differentiation. Monolayer cultures of HBMSCs were treated for 3 days with the 5-aza-dC or TSA, followed by culture in the absence of modifiers. Cells were subsequently grown in pellet culture to determine matrix production. 5-aza-dC stimulated osteogenic differentiation as evidenced by enhanced alkaline phosphatase activity, increased Runx-2 expression in monolayer, and increased osteoid formation in 3D cell pellets. In pellets cultured in chondrogenic media, TSA enhanced cartilage matrix formation and chondrogenic structure. These findings indicate the potential of epigenetic modifiers, as agents, possibly in combination with other factors, to enhance the ability of HBMSCs to form functional bone or cartilage with significant therapeutic implications therein.

Place, publisher, year, edition, pages
London, United Kingdom: Elsevier, 2011. Vol. 81, no 1, p. 35-41
Keywords [en]
5-aza-deoxycytidine; Trichostatin A; Skeletal stem cells; Chondrogenesis; Osteogenesis; Epigenetics
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-184631DOI: 10.1016/j.diff.2010.09.183ISI: 000284826700004PubMedID: 20970916Scopus ID: 2-s2.0-78649663944OAI: oai:DiVA.org:liu-184631DiVA, id: diva2:1654715
Note

Funding: The authors thank the Orthopaedic Surgeons at Southampton General Hospital for provision of bone marrow. We thank the Egyptian government for funding Dr. Serafi's Ph.D. and the BBSRC for research support to ROCO.

Available from: 2022-04-28 Created: 2022-04-28 Last updated: 2022-05-05Bibliographically approved

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El-Serafi, Ahmed Taher

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