The Absence of Syndecan‐1 Leads to More Inflammation in the Mouse Model of Rheumatoid Arthritis

Abstract

Introduction Syndecan-1 (sdc-1) is a member of a family of transmembrane proteoglycans expressed in numerous cell types. It has been shown to be involved in carcinogenesis, wound healing and inflammation. However, its potential role in the pathophysiology of Rheumatoid Arthritis (RA) has not been well elucidated yet. Many modified mouse strains are relatively resistant to collagen-induced RA, while others could acquire it spontaneously. Such strains have been very useful for assessing therapeutics with anti-inflammatory properties. Aim Evaluate the potential role of sdc-1 in the development of RA using sdc-1 null mice. Hypothesis We hypothesized that inflammation will be more severe in the absence of sdc-1. Methods A total of 18 mice (9 BALB/c wild type and 9 sdc-1 null), 8-10 weeks old, were divided into 6 groups. They were injected with different concentrations of Collagen II (CII) and Complete Freund's Adjuvant (CFA) to induce arthritis. A two-dose regimen, three weeks apart, was followed (Table 1). The mice were monitored three times a week for 70 days and clinical signs of redness and swelling were recorded. Routine histological studies of joint biopsies were also performed using different stains, including Safranin O for cartilage and bone. Results Preliminary data demonstrated the following: Clinical signs and symptoms:redness and swelling of joints appeared earlier in the sdc-1 null group injected with 75µl CII + 75µl CFA compared to the BALB/c group with similar treatment (Figure 1). Histological assessment: the joints of sdc-1 null mice showed more alterations: marked atrophy and loss of articular cartilage, increased infiltration by inflammatory cells specifically macrophages, subchondral bone porosity, changes in the trabecular network as well as bone erosion. All mice treated with collagen showed increased proteoglycan content in the articular cartilage and growth plate. Conclusion Sdc-1 null mice developed a faster and more severe experimental RA; however, more characterization at the macroscopic, microscopic and molecular level is needed. Uncovering the role of sdc-1 in RA paves the way for future investigations that can lead to the emergence of new therapeutic modalities that could be adopted along with conventional treatments.