Background The syndecans (SDCs) are integral cell surface heparan sulfate proteoglycans (HSPGs) that are expressed in a cell, tissue and development specific manner. To date, the regulation of SDC-1 expression in synovial tissues (ST) of rheumatoid arthritis (RA) has not been uncovered.
Objectives The aims of this study were to delineate the expression of SDC-1 on subsets of inflammatory cells in RA-ST and to investigate regulatory pathways involved in its expression.
Methods ST was obtained during patients with RA and OA during joint replacement surgery. Expression of SDC-1 and other cell markers in ST was evaluated with immunohistochemical (IHC) and immunofluorescence (IF) staining. Synthesis of SDC-1 was determined by semi-quantitative RT-PCR, western blot, and flow cytometry. A murine collagen-induced arthritis (CIA) model was used for evaluation of SDC-1 expression at different stages of arthritis.
Results The expression of SDC-1 was upregulated in subsets of cells in RA-ST compared with those in OA-ST. SDC-1 was expressed on the surface of CD68+ and CD11c+ cells as well as CD38+ cells. CD68+SDC-1+cells were mainly localized at the periphery of follicular structure where critical cell-cell interactions take place and a subset of lining cells. SDC-1 was highly upregulated in monocytes from RA synovial fluid compared with those from peripheral blood of RA and normal controls. The upregulated expression of SDC-1 on classically activated macrophages compared to CD14+ monocytes was inhibited by either JNK- or NF-kB inhibitors, but not by ERK and p38 MAPKinase inhibitors. To confirm if SDC-1 is differentially expressed at different stages of arthritis development, CIA mice were used. SDC-1 expression was increased from the early stages of arthritis and was most remarkable at cartilage-pannus junctions in advanced arthritis. Treatment with methotrexate clearly reduced the SDC-1 expression in CIA mice.
Conclusions The expression of SDC-1, which is upregulated in ST of inflammatory arthritis according to disease progression, was increased in monocytes/macrophages in a JNK- and NF-kB-dependent manner. These results underscore the existence of pathways by which SDC-1 expression was regulated in the inflammatory context of RA.
Disclosure of Interest None Declared