Effects of Trichostatin A on the Chondrogenesis from Human Mesenchymal Stem Cells

Jimin Lee, Gun Il Im

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Histone deacetylase inhibitors (HDACi) are a class of compounds that suppress the function of histone deacetylases (HDACs). This study was performed to examine the effects of Trichostatin A (TSA), a typical HDACi, on chondrogenesis of human bone marrow mesenchymal stem cells (hBMMSCs) and related molecular pathways. After evaluating the concentration for cytotoxicity and HDAC activity, hBMMSCs underwent chondrogenic differentiation in pellet culture with or without TSA for 21 days. The weight of TSA-treated pellets was 25% lower than that of untreated pellets. DNA level was not significantly different, but glycosaminoglycan content per DNA level was lower in TSA-treated pellets than that of untreated pellets. Gene expression of the chondrogenic markers (SOX9, Aggrecan, and Col2A1) decreased by by 12.9-fold, 8.9-fold, and 7.6-fold respectively in TSA-treated pellets compared with that in TSA-untreated pellets. TSA-treated pellets had lower cell density and lower proteoglycan staining content compared with those of TSA-untreated pellets. A microarray analysis from TSA-treated pellets showed that 1,467 chondrogenic-related genes were downregulated and 1,524 were upregulated by more than 2-fold compared with TSA-untreated pellets. Col10A1, TGF-β3, and SOX9 decreased significantly by 10-fold, 2.1-fold, and 3.2-fold respectively in TSA-treated pellets compared with those in untreated pellets, whereas expression of BMP4 and FGFR3 increased significantly by 2.1-fold and 5.4-fold respectively. It is concluded that TSA inhibits chondrogenesis and does not seem to be useful for cartilage tissue engineering of hBMMSCs.

Original languageEnglish
Pages (from-to)403-410
Number of pages8
JournalTissue Engineering and Regenerative Medicine
Volume14
Issue number4
DOIs
StatePublished - 1 Aug 2017

Keywords

  • Chondrogenesis
  • Differentiation
  • Gene profiling
  • HDAC inhibitor
  • TSA

Fingerprint

Dive into the research topics of 'Effects of Trichostatin A on the Chondrogenesis from Human Mesenchymal Stem Cells'. Together they form a unique fingerprint.

Cite this