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Biologicals. 2017 Jan;45:96-101. doi: 10.1016/j.biologicals.2016.09.013. Epub 2016 Oct 20.

Applicability of human osteoarthritic chondrocytes for in vitro efficacy testing of anti-TNFα drugs.

Author information

1
Educell Cell Therapy Service Ltd., Prevale 9, 1236 Trzin, Slovenia. Electronic address: sara.zigon@educell.si.
2
Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia; Celica Biomedical Ltd., Tehnološki Park 24, 1000 Ljubljana, Slovenia. Electronic address: Matjaz.Jeras@ffa.uni-lj.si.
3
National Institute of Biology, Večna pot 101, 1000 Ljubljana, Slovenia. Electronic address: Andrej.Blejec@nib.si.
4
Educell Cell Therapy Service Ltd., Prevale 9, 1236 Trzin, Slovenia. Electronic address: ariana.barlic@educell.si.

Abstract

In vitro cell-based models are important tools for assessing efficacies of new leads in early phases of drug development. Human osteoarthritic chondrocytes (OACs), obtained from biomedical waste material, represent a valuable, relatively accessible cellular source that could be used for this purpose. By employing reverse transcription-polymerase chain reaction (qRT-PCR) we compared gene expression profiles of key anabolic, catabolic and inflammatory genes of freshly isolated vs. monolayer cultured OACs (passages P0-P2) and non-stimulated vs. tumor necrosis factor alpha (TNF-α) stimulated P2 OACs. After expansion of OACs in monolayer cultures, the expression of almost all analyzed genes significantly decreased. The subsequent addition of TNF-α to OACs at P2 significantly increased expressions of all catabolic and inflammatory genes, leaving the anabolic profile almost unchanged. TNF-α-treated OACs were later utilized for efficacy testing of anti-TNF-α drugs infliximab and etanercept and both significantly reduced the expressions of all catabolic and inflammatory genes tested.

KEYWORDS:

Gene expression; Human osteoarthritic chondrocytes (OACs); In vitro drug testing; TNF-α

[Indexed for MEDLINE]

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