Improving chondrogenesis: potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering

Kupcsik, L; Stoddart, MJ; Li, Z; Benneker, LM; Alini, M (2010). Improving chondrogenesis: potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering. Tissue engineering. Part A, 16(6), pp. 1845-55. New Rochelle, N.Y.: Mary Ann Liebert 10.1089/ten.tea.2009.0531

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Articular cartilage injuries and degeneration affect a large proportion of the population in developed countries world wide. Stem cells can be differentiated into chondrocytes by adding transforming growth factor-beta1 and dexamethasone to a pellet culture, which are unfeasible for tissue engineering purposes. We attempted to achieve stable chondrogenesis without any requirement for exogenous growth factors. Human mesenchymal stem cells were transduced with an adenoviral vector containing the SRY-related HMG-box gene 9 (SOX9), and were cultured in a three-dimensional (3D) hydrogel scaffold composite. As an additional treatment, mechanical stimulation was applied in a custom-made bioreactor. SOX9 increased the expression level of its known target genes, as well as its cofactors: the long form of SOX5 and SOX6. However, it was unable to increase the synthesis of sulfated glycosaminoglycans (GAGs). Mechanical stimulation slightly enhanced collagen type X and increased lubricin expression. The combination of SOX9 and mechanical load boosted GAG synthesis as shown by (35)S incorporation. GAG production rate corresponded well with the amount of (endogenous) transforming growth factor-beta1. Finally, cartilage oligomeric matrix protein expression was increased by both treatments. These findings provide insight into the mechanotransduction of mesenchymal stem cells and demonstrate the potential of a transcription factor in stem cell therapy.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery
UniBE Contributor:	Benneker, Lorin Michael
ISSN:	1937-3341
Publisher:	Mary Ann Liebert
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:08
Last Modified:	05 Dec 2022 14:00
Publisher DOI:	10.1089/ten.tea.2009.0531
PubMed ID:	20067399
Web of Science ID:	000278164800005
URI:	https://boris.unibe.ch/id/eprint/740 (FactScience: 200664)