Applicability of human osteoarthritic chondrocytes for in vitro efficacy testing of anti-TNF alpha drugs

摘要

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 PO-P2) and non-stimulated vs. tumor necrosis factor alpha (TNF-alpha) stimulated P2 OACs. After expansion of OACs in monolayer cultures, the expression of almost all analyzed genes significantly decreased. The subsequent addition of INF-alpha to OACs at P2 significantly increased expressions of all catabolic and inflammatory genes, leaving the anabolic profile almost unchanged. TNF-alpha-treated OACs were later utilized for efficacy testing of anti-TNF-alpha drugs infliximab and etanercept and both significantly reduced the expressions of all catabolic and inflammatory genes tested. (C) 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.