Bone destruction by receptor activator of nuclear factor κB ligand-expressing T cells in chronic gouty arthritis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-10

AUTHORS

Sung-Ji Lee, Kwang-Il Nam, Hye-Mi Jin, Young-Nan Cho, Song-Eun Lee, Tae-Jong Kim, Shin-Seok Lee, Seung-Jung Kee, Keun-Bae Lee, Nacksung Kim, Yong-Wook Park

ABSTRACT

INTRODUCTION: 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. More... »

PAGES

r164

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/ar3483

DOI

http://dx.doi.org/10.1186/ar3483

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026802760

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21992185


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