Bone destruction by receptor activator of nuclear factor κB ligand-expressing T cells in chronic gouty arthritis
- Equal contributors
1 Department of Rheumatology, Research Institute of Medical Sciences, Brain Korea 21, Chonnam National University Medical School and Hospital, 42, Jebong-ro, Dong-gu, Gwangju 501-757, South Korea
2 Department of Anatomy, Chonnam National University Medical School, 42, Jebong-ro, Dong-gu, Gwangju 501-757, South Korea
3 Department of Laboratory Medicine, Chonnam National University Medical School and Hospital, 42, Jebong-ro, Dong-gu, Gwangju 501-757, South Korea
4 Department of Orthopedic Surgery, Chonnam National University Medical School and Hospital, 42, Jebong-ro, Dong-gu, Gwangju 501-757, South Korea
5 National Research Laboratory for Regulation of Bone Metabolism and Disease, Medical Research Center for Gene Regulation, Chonnam National University Medical School, 42, Jebong-ro, Dong-gu, Gwangju 501-757, South Korea
Arthritis Research & Therapy 2011, 13:R164 doi:10.1186/ar3483Published: 13 October 2011
The purpose of this study was to analyze the cellular expressions of pro-resorptive cytokines in gouty tophus tissues, to determine the capacity of monosodium urate monohydrate (MSU) crystals to induce these cytokines, and to understand the mechanisms of bone destruction in chronic gout.
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).
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 was 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.
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.