title: Bone destruction by receptor activator of nuclear factor κB ligand-expressing T cells in chronic gouty arthritis.
abstract: BACKGROUND
  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.
  
  
  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 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.
  
  
  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.
authors: 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.
authors: Sung-Ji
authors: SJ
authors: Lee
authors: Kwang-Il
authors: KI
authors: Nam
authors: Hye-Mi
authors: HM
authors: Jin
authors: Young-Nan
authors: YN
authors: Cho
authors: Song-Eun
authors: SE
authors: Lee
authors: Tae-Jong
authors: TJ
authors: Kim
authors: Shin-Seok
authors: SS
authors: Lee
authors: Seung-Jung
authors: SJ
authors: Kee
authors: Keun-Bae
authors: KB
authors: Lee
authors: Nacksung
authors: N
authors: Kim
authors: Yong-Wook
authors: YW
authors: Park
mesh_terms: D000328:Adult; D000368:Aged; D015210:Arthritis, Gouty / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology*
chemical_list: D053245:RANK Ligand; C505688:TNFSF11 protein, human