title: Applicability of human osteoarthritic chondrocytes for in vitro efficacy testing of anti-TNFα drugs.
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.
authors: Educell Cell Therapy Service Ltd., Prevale 9, 1236 Trzin, Slovenia. Electronic address: sara.zigon@educell.si.
authors: Sara
authors: S
authors: Žigon-Branc
authors: 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.
authors: Matjaž
authors: M
authors: Jeras
authors: National Institute of Biology, Večna pot 101, 1000 Ljubljana, Slovenia. Electronic address: Andrej.Blejec@nib.si.
authors: Andrej
authors: A
authors: Blejec
authors: Educell Cell Therapy Service Ltd., Prevale 9, 1236 Trzin, Slovenia. Electronic address: ariana.barlic@educell.si.
authors: Ariana
authors: A
authors: Barlič
mesh_terms: D000368:Aged; D019902:Chondrocytes / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000068800:Etanercept / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept
keywords: Gene expression; Human osteoarthritic chondrocytes (OACs); In vitro drug testing; TNF-α