Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 848604, 13 pages
http://dx.doi.org/10.1155/2014/848604
Research Article

Development and Retranslational Validation of an In Vitro Model to Characterize Acute Infections in Large Human Joints

Department of Orthopedic Surgery, University of Freiburg Medical Center, Hugstetter Straße 55, 79106 Freiburg, Germany

Received 3 September 2013; Accepted 9 April 2014; Published 30 April 2014

Academic Editor: Shigeru Kotake

Copyright © 2014 Ingo H. Pilz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Bacterial infections can destroy cartilage integrity, resulting in osteoarthritis. Goal was to develop an in vitro model with in vivo validation of acute joint inflammation. Inflammation in cocultivated human synovial fibroblasts (SFB), chondrocytes (CHDR), and mononuclear cells (MNC) was successively relieved for 10 days. Articular effusions from patients with ( ) and without ( ) postoperative joint infection in healthy patients (ASA 1-2) were used as model validation. Inflammation in vitro resulted in an enormous increase in IL-1 and a successive reduction in SFB numbers. CHDR however, maintained metabolic activity and proteoglycan synthesis. While concentrations of bFGF in vivo and in vitro rose consistently, the mRNA increase was only moderate. Concurring with our in vivo data, cartilage-specific IGF-1 steadily increased, while IGF-1 mRNA in the CHDR and SFB did not correlate with protein levels. Similarly, aggrecan (ACAN) protein concentrations increased in vivo and failed to correlate in vitro with gene expression in either the CHDR or the SFB, indicating extracellular matrix breakdown. Anabolic cartilage-specific BMP-7 with highly significant intra-articular levels was significantly elevated in vitro on day 10 following maximum inflammation. Our in vitro model enables us to validate early inflammation of in vivo cell- and cytokine-specific regulatory patterns. This trial is registered with MISSinG, DRKS 00003536.