Rheumatology Advance Access originally published online on October 12, 2004
Rheumatology 2005 44(2):164-171; doi:10.1093/rheumatology/keh431
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Rheumatology Vol. 44 No. 2 © British Society for Rheumatology 2004; all rights reserved
Inflammatory status and cartilage regenerative potential of synovial fibroblasts from patients with osteoarthritis and chondropathy
Laboratoire d’Immunologie, Université Montpellier-1, Polyclinique St Roch, Montpellier, Inserm U602, Hôpital Paul Brousse, Villejuif, France, 1 La Sapienza University, Rome, Italy, 2 Polyclinique St Roch, Montpellier, France and 3 U602, Hôpital Paul Brousse, Bátiment Lavoisier, 12–16 avenue Paul Vaillant Couturier, Villejuif, France.
Correspondence to: D. Brouty-Boyé, Inserm U602, Hôpital Paul Brousse, Bâtiment Lavoisier, 12–16 avenue Paul Vaillant-Couturier, 94807 Villejuif cedex, France. E-mail: brouty{at}vjf.inserm.fr
Objectives. To evaluate the inflammatory status and the cartilage regenerative potential of pathological synovial fibroblasts from patients with osteoarthritis (OA) compared with non-inflamed synovium (NS)-derived cells from patients with chondropathy.
Methods. The inflammatory cell phenotype was investigated based on the constitutive and inducible surface expression and secretion of various effector molecules using flow cytometry or ELISA assays. The capacity of cells to produce cartilage-like extracellular matrix was assessed using acid Alcian blue staining and type II collagen immunostaining after treatment with transforming growth factor ß1 (TGF-ß1).
Results. OA and NS fibroblasts consistently expressed CD29, CD44, CD49e, CD54, CD90 and CD106. Expression of high-affinity receptors for IL-4, IL-15, CXCL8 and CXCL12 was also detected but only intracellularly. All types of fibroblasts spontaneously released abundant amounts of CXCL12, CCL2, IL-6 and tissue inhibitor of metalloproteinase 1, while the production of IL-11, TGF-ß1, matrix metalloproteinase 1 (MMP-1) and MMP-9 was detected at moderate levels. Several other secreted factors remained undetectable. No statistically significant differences were noted between the two groups of fibroblasts. Treatment with the proinflammatory cytokine tumour necrosis factor 
(TNF-) up-regulated the same set of surface and secreted molecules, including CD54, CD106, membrane IL-15, CCL2 and CCL5. Under TGF-ß1 treatment and adipogenic culture conditions, both OA and NS fibroblasts displayed chondrogenic and adipocytic activities that were reduced in OA compared with NS cells.
Conclusions. OA synovial fibroblasts did not display a distinct activated inflammatory phenotype compared with NS cells. However, they did differ in their reduced ability to produce cartilage-like matrix. This difference may be an additional important factor contributing to OA pathogenesis.
KEY WORDS: Synovial fibroblast, Inflammatory phenotype, Chondrogenic activity, Osteoarthritis, Chondropathy