The University of Southampton
University of Southampton Institutional Repository

Epigenetic modifiers influence lineage commitment of human bone marrow stromal cells: Differential effects of 5-aza-deoxycytidine and trichostatin A

Epigenetic modifiers influence lineage commitment of human bone marrow stromal cells: Differential effects of 5-aza-deoxycytidine and trichostatin A
Epigenetic modifiers influence lineage commitment of human bone marrow stromal cells: Differential effects of 5-aza-deoxycytidine and trichostatin A
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.

5-aza-deoxycytidine, trichostatin a, skeletal stem cells, chondrogenesis, osteogenesis, epigenetics
0301-4681
35-41
El-Serafi, Ahmed T.
1793a0ca-2579-4350-9de3-65ee57ccbb6b
Oreffo, Richard O.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Roach, Helmtrud I.
ca2ff1f4-1ada-4c56-9097-cd27ca4d199e
El-Serafi, Ahmed T.
1793a0ca-2579-4350-9de3-65ee57ccbb6b
Oreffo, Richard O.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Roach, Helmtrud I.
ca2ff1f4-1ada-4c56-9097-cd27ca4d199e

El-Serafi, Ahmed T., Oreffo, Richard O. and Roach, Helmtrud I. (2011) Epigenetic modifiers influence lineage commitment of human bone marrow stromal cells: Differential effects of 5-aza-deoxycytidine and trichostatin A. Differentiation, 81 (1), 35-41. (doi:10.1111/(ISSN)1432-0436). (PMID:20970916)

Record type: Article

Abstract

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.

This record has no associated files available for download.

More information

Published date: January 2011
Keywords: 5-aza-deoxycytidine, trichostatin a, skeletal stem cells, chondrogenesis, osteogenesis, epigenetics

Identifiers

Local EPrints ID: 181647
URI: http://eprints.soton.ac.uk/id/eprint/181647
ISSN: 0301-4681
PURE UUID: 54e33427-d19d-4c04-ad53-1668163007ca
ORCID for Richard O. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

Catalogue record

Date deposited: 18 Apr 2011 14:15
Last modified: 15 Mar 2024 03:03

Export record

Altmetrics

Contributors

Author: Ahmed T. El-Serafi
Author: Helmtrud I. Roach

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×