Pathomechanism Of Bone Destruction In Chronic Gouty Arthritis

Background Gout is an inflammatory arthritis caused by the deposition of monosodium urate monohydrate (MSU) crystals within joints during chronic hyperuricemia. Chronic tophaceous gout may lead to bone destruction by osteoclastogenesis. However, the cellular mechanisms by which of cytokines are involved in osteoclastogenesis in response to MSU crystals remain to be clarified. Objectives The aims of this study is to analyze the cellular expressions of pro-resorptive cytokines in gouty tophus tissues, to determine the capacity of MSU crystals to induce these cytokines, and to understand the mechanisms of bone destruction in chronic gout. Methods Fourteen fixed, paraffin-embedded, uninfected tophus samples were analyzed immunohistochemically. Peripheral blood mononuclear cells (PBMCs) were cultured in vitro with MSU crystals, and gene expression was assessed by reverse transcription-polymerase chain reaction. In vitro osteoclastogenesis was performed using PBMCs and synovial fluid mononuclear cells (SFMCs). Results CD4+ T cells, CD8+ T cells, CD20+ B cells, and mast cells infiltrated tophus tissues. Tartrate-resistant acid phosphatase (TRAP)+ osteoclasts were present around tophi and in osteolytic lesions. Interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha were produced from infiltrated mononuclear cells, whereas receptor activator of nuclear factor κB ligand (RANKL) was strongly expressed in T cells. However, osteoprotegerin (OPG) was not or weakly expressed in tophus tissues. MSU crystals induced the expressions of IL-1, IL-6, TNF-alpha and RANKL in PBMCs, but inhibited OPG expression. In addition, the pro-resorptive cytokines were highly expressed in SFMCs of gouty arthritis patients. Furthermore, in vitro osteoclastogenesis was enhanced in SFMC cultures, but inhibited in T cell-depleted SFMC cultures. Conclusions Our study demonstrates that RANKL-expressing T cells and TRAP+ osteoclasts are present within gouty tophus tissues, and that infiltrating cells express pro-resorptive cytokines. Furthermore, our data show that MSU crystals have the potential to induce pro-resorptive cytokines, and T cells are involved in osteoclastogenesis in chronic gout. Disclosure of Interest None Declared