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SAT0069 Regulation of syndecan-1 expression in monocytes/macrophages in chronic inflammatory arthritis
  1. M.M. Alam,
  2. J.H. Kang,
  3. J.A. Jang,
  4. K.H. Sa,
  5. E.J. Nam,
  6. Y.M. Kang
  1. Internal Medicine (Rheumatology), Kyungpook National University Hospital, Daegu, Korea, Republic Of

Abstract

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

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