Publisher DOI: 10.1016/j.gene.2019.02.065
Title: Secreted factors from synovial fibroblasts immediately regulate gene expression in articular chondrocytes
Language: English
Authors: Bonitz, Martin 
Schaffer, Christiane 
Amling, Michael 
Pörtner, Ralf  
Schinke, Thorsten 
Jeschke, Anke 
Keywords: Articular chondrocyte;Matrix metalloproteinases;Osteoarthrtis;Syndecan-4;Synovial fibroblast
Issue Date: 25-Feb-2019
Publisher: Elsevier
Source: Gene (698): 1-8 (2019-02-25)
Journal or Series Name: Gene 
Abstract (english): 
Although articular cartilage degeneration in osteoarthritis represents a major public health problem, there is still no molecular approach to prevent this pathology by blocking specific molecules. We have previously applied genome-wide expression analyses with porcine samples to identify specific markers of either growth plate or articular cartilage. Since the molecular differences were also found in cultured chondrocytes derived from both sites, we utilized primary porcine articular chondrocytes (PPACs) for the present study and analyzed, if and how they respond to synoviocyte-derived molecules. PPACs were treated by conditioned medium from porcine synovial fibroblasts (SF-CM) for 2, 6 and 24 h. Gene expression was subsequently monitored by qRT-PCR and microarray analysis. We found that short-term administration of SF-CM to PPACs significantly reduced expression of chondrocyte markers, while it induced expression of SDC4, encoding syndecan-4, a positive regulator of articular cartilage breakdown. Consistently, expression of MMP3, a putative downstream effector of syndecan-4 was strongly induced by SF-CM in PPACs. We identified an MMP3-inducing fraction in the range of 40 kDa after gel filtration, and we confirmed our findings in three-dimensional PPAC cultures, where SF-CM also reduced the glycosaminoglycan content. Taken together, our data suggest that synovial fibroblasts secrete one or more molecule(s) that activate specific signaling events in articular chondrocytes. Identifying a responsible ligand receptor pair(s) might pave the way to develop molecular therapies to reduce the severity of osteoarthritis.
ISSN: 0378-1119
Institute: Bioprozess- und Biosystemtechnik V-1 
Document Type: Article
Funded by: This study was funded by the German Research Foundation (DFG) (PO 413/14-1 , AM 103/21-1 ).
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