FOXO1, PXK, PYCARD and SAMD9L are differentially expressed by fibroblast-like cells in equine synovial membrane compared to joint capsule

Abstract Background The synovial membrane lines the luminal side of the joint capsule in synovial joints. It maintains joint homeostasis and plays a crucial role in equine joint pathology. When trauma or inflammation is induced in a joint, the synovial membrane influences progression of joint damage. Equine synovial membrane research is hampered by a lack of markers of fibroblast-like synoviocytes (FLS) to distinguish FLS from other fibroblast-like cells in musculoskeletal connective tissues. The aim of this study is to identify potential FLS markers of the equine synovial membrane using microarray to compare between gene expression in equine synovial membrane and the joint capsule in metacarpophalangeal joints. Results Microarray analysis of tissues from 6 horses resulted in 1167 up-regulated genes in synovial membrane compared with joint capsule. Pathway analysis resulted in 241 candidate genes. Of these, 15 genes were selected for further confirmation as genes potentially expressed by fibroblast-like synoviocytes. Four genes: FOXO1, PXK, PYCARD and SAMD9L were confirmed in 9 horses by qPCR as differentially expressed in synovial membrane compared to joint capsule. Conclusions In conclusion, FOXO1, PXK, PYCARD and SAMD9L were confirmed as differentially expressed in synovial membrane compared to joint capsule. These four genes are potential markers of fibroblast-like synoviocytes of the synovial membrane. As these genes are overexpressed in synovial membrane compared to joint capsule, these genes could shed light on synovial membrane physiology and its role in joint disease

Differential inhibitory effects of indomethacin, dexamethasone, and interferon-gamma (IFN-γ) on IL-11 production by rheumatoid synovial cells

IL-11, a member of the IL-6 type cytokines, has some biological activity related to the joint destruction in rheumatoid arthritis (RA), such as induction of osteoclast differentiation. However, its expression and regulation in rheumatoid inflamed joints has not been clarified. In the present study we examined the capacity of fresh rheumatoid synovial cells (fresh RSC) to produce IL-11, and the effect of indomethacin, dexamethasone and IFN-γ on IL-11 production. Fresh RSC obtained from eight patients with RA produced large amounts of IL-11, measured by ELISA, and showed strong expression of IL-11 mRNA, determined by Northern blotting. Indomethacin inhibited the production of IL-11 by about 55%. Prostaglandin E2 (PGE2) completely prevented the inhibition, suggesting that IL-11 production by fresh RSC was in part mediated by PGE2. Dexamethasone inhibited the production of IL-11 by more than 80%. Interestingly, the inhibition was not abolished by PGE2. IFN-γ inhibited the production of IL-11 from IL-1α-stimulated cultured rheumatoid synovial fibroblasts, although IFN-γ did not inhibit the production of IL-11 by fresh RSC. These results suggest that the production of IL-11 by rheumatoid synovia was differentially regulated by PGE2 and IFN-γ, and that treatment with indomethacin or dexamethasone decreased the level of IL-11 at inflammatory joints in patients with RA