Background and objectives Osteoarthritis, characterised by a gradual progression of extracellular matrix (ECM) degradation, has been traditionally classified as a cartilage disease. However the new paradigm is that in OA the whole joint is involved, the cartilage but also synovium, subchondral bone and supporting structures, such as meniscus and the acetabular labrum. These supporting structures however remain largely unstudied. The acetabular labrum, is a fibrocartilageous horseshoe-shaped structure sealing the hip joint. We had previously proven that labrum cells are active in ECM synthesis and are able the react to pro-inflammatory cytokines. In this study our goal was to investigate hip OA specific gene expression changes in these cells in comparison with chondrocytes. Furthermore we aimed to investigate the functional importance of these gene expression differences.
Material and methods Labrum cells from 5 OA patients en 3 healthy control patients were isolated and cultured in the 3-Dimensional alginate culture system. A genome wide gene expression analysis was performed using the Affymetrix microarray technology. Differential gene expression levels were confirmed on additional patient samples by quantitative PCR (qPCR), western blot and immunohistochemistry. Functional studies were performed by addition of recombinant protein the 3D-alginate labrum cultures.
Results Pathway analysis performed on the microarray data indicate a distinct OA gene expression pattern in labrum cells, characterised by an increased cytokine and chemokine signalling as well as a reduced ECM receptor interaction and TGFβ signalling. Several genes were differentially regulated in OA compared to healthy labrum cells. We specifically focused on three proteins members of the short leucine rich repeat protein (SLRP) family: osteomodulin (OMD), osteoglycin (OGN) and asporin (ASPN). These proteins were found to be significantly downregulated in OA labrum but upregulated in OA cartilage. Moreover in vitro stimulation with OMD was able to induce proteoglycan synthesis in labrum cells.
Conclusion Several features of OA chondrocytes are shared by OA labrum fibrochondrocytes, however SLRP expression seems to be differentially influenced in labrum compared to cartilage by OA degeneration. This suggest a distinct role for this supporting structure in hip OA, in which SLRP may play an important part.
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