Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors

Iannis Adamopoulos, Cheng chi Chao, Richard Geissler, Drake Laface, Wendy Blumenschein, Yoichiro Iwakura, Terrill McClanahan, Edward P. Bowman

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

Introduction: The interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.Methods: Human CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-κB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice.Results: IL-17A upregulates the receptor activator for NF-κB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts.Conclusions: Collectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases.

Original languageEnglish (US)
Article numberR29
JournalArthritis Research and Therapy
Volume12
Issue number1
DOIs
StatePublished - Feb 18 2010
Externally publishedYes

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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    Adamopoulos, I., Chao, C. C., Geissler, R., Laface, D., Blumenschein, W., Iwakura, Y., McClanahan, T., & Bowman, E. P. (2010). Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors. Arthritis Research and Therapy, 12(1), [R29]. https://doi.org/10.1186/ar2936