title: Differential adherence of osteoarthritis and rheumatoid arthritis synovial fibroblasts to cartilage and bone matrix proteins and its implication for osteoarthritis pathogenesis.
abstract: In osteoarthritis (OA), cartilage and bone fragments have been described within the synovial tissue which are surrounded by synovial cells (i.e. detritus synovitis). These cells appear to attach actively to the cartilage and bone fragments. In rheumatoid arthritis (RA), on the other hand, synovial fibroblasts (SF) have also been shown to be localized at sites of invasion into cartilage and bone and to degrade extracellular matrix (ECM) by secreting proteolytic enzymes. One prerequisite for exerting their aggressive properties is the attachment to cartilage and bone ECM. This attachment appears to be mediated by the expression of different adhesion molecules for which corresponding binding sites on ECM components are known. As it has not been addressed to which ECM proteins SF adhere and with which affinity this process takes place, we investigated the adherence of SF from patients with OA and RA to different cartilage and bone matrix proteins. Synovial tissue samples were obtained during synovectomy or arthroplastic surgery and used for isolating and culturing SF. Synovial cells attaching to cartilage/bone fragments were characterized using immunohistochemistry. The adherence of SF to ECM proteins was examined using an adhesion assay with the following proteins coated on 96-well plates: aggrecan (AGG), bone sialoprotein (BSP), cartilage oligomeric matrix protein (COMP), collagen type I, II and VI, proline arginine-rich, end leucine-rich repeat protein (PRELP), osteopontin (OPN) and recombinant chondroadherin (CHAD). Bovine serum albumin was used as negative control. In addition, adhering fibroblasts were photographed using a phase-contrast microscope. As compared with RA-SF, significantly higher numbers of OA-SF adhering to collagen type II, OPN and CHAD could be detected (P < 0.05). In contrast, RA-SF showed increased attachment to collagen type II, OPN and BSP. Adhesion to AGG, COMP and PRELP appeared not to be significantly increased and differed widely among the SF samples, and, apart from one exception (BSP), OA-SF adhered in higher numbers to the matrix proteins than did RA-SF. Using immunohistochemistry, synovial cells attached to cartilage/bone fragments could be shown to predominantly express CD68 (>/=50%). The CD68-negative population was of the fibroblast phenotype (AS02 positive). The study demonstrates that the binding pattern of OA-SF and RA-SF to ECM proteins differs considerably and therefore provides novel insights into the difficult pathophysiology of OA and RA. In general, it appeared that SF adhere primarily to ECM proteins that contain known binding sites for adhesion molecules (e.g. integrins: collagen/integrin alpha(2)beta(1)) and that higher numbers of OA-SF adhered to the cartilage and bone matrix proteins than did RA-SF.
authors.affiliation: Department of Internal Medicine I, Division of Rheumatology and Clinical Immunology, University Hospital of Regensburg, Regensburg, Germany. joerg.schedel@klinik.uni-regensburg.de
authors.forename: J
authors.initials: J
authors.lastname: Schedel
authors.forename: C
authors.initials: C
authors.lastname: Wenglén
authors.forename: O
authors.initials: O
authors.lastname: Distler
authors.forename: U
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: J
authors.initials: J
authors.lastname: Schölmerich
authors.forename: D
authors.initials: D
authors.lastname: Heinegård
authors.forename: V
authors.initials: V
authors.lastname: Krenn
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001857:Bone Matrix / Q000276:immunology*; D002356:Cartilage / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D010003:Osteoarthritis / Q000209:etiology / Q000276:immunology*; D013583:Synovial Membrane / Q000276:immunology*