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

Discrepancy between mRNA and protein expression of tumour suppressor maspin in synovial tissue may contribute to synovial hyperplasia in rheumatoid arthritis

“…Furthermore, the ability of recombinant maspin to inhibit the invasive process of these cells could be abrogated with a blocking antibody to the a5b1 integrin, which diminished the ability of cells to invade through a fibronectin matrixcontaining barrier in vitro, 21 supporting the idea that maspin alters the integrin profile rendering cells more adhesive, but less invasive. 21 As increased expression of integrins containing a5 and b1 has been described in RA synovial tissue, 22 23 and as RA SF could be shown to be less adhesive to collagen and other extracellular matrix components than OA SF, 24 these properties of RA SF might be due to the down regulation of maspin seen in the present study.…”

Early structural changes in cartilage and bone are required for the attachment and invasion of inflamed synovial tissue during destructive inflammatory arthritis

“…In addition to integrins, transmembrane heparan sulfate proteoglycans of the syndecan family are involved in the attachment of cells to matrix components and there is evidence for a specific contribution of syndecan-4 in the activation of SFs 8. Nonetheless, the relevance of individual adhesion molecules as well as their specific binding partners in healthy and diseased cartilage has not been clarified, and recent data9 have complicated the picture by showing no significant differences in the overall attachment behaviour between RA SFs and osteoarthritis SFs.…”

Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation

“…A study on OSAD in rat primarily showed expression in bone marrow and in bone directly under articular cartilage forming in the femoral head (Shen et al, 1999). Furthermore, CHAD was recently demonstrated to promote rapid spreading of synovial fibroblasts from osteoarthritis (OA) patients, implicating a role in OA pathology (Schedel et al, 2004). …”