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

123 Citations (Scopus)

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

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Interleukin-17
Osteoclasts
Up-Regulation
Bone and Bones
Osteogenesis
Autoimmune Diseases
Bone Marrow
Macrophages
Osteoprotegerin
Gene Flow
Bone Remodeling
Dentin
Fluorescence Microscopy
Immune System
Rheumatoid Arthritis
Electron Microscopy
Flow Cytometry
Homeostasis
Tomography
Staining and Labeling

ASJC Scopus subject areas

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

Cite this

Adamopoulos, I., Chao, C. C., Geissler, R., Laface, D., Blumenschein, W., Iwakura, Y., ... 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

Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors. / Adamopoulos, Iannis; Chao, Cheng chi; Geissler, Richard; Laface, Drake; Blumenschein, Wendy; Iwakura, Yoichiro; McClanahan, Terrill; Bowman, Edward P.

In: Arthritis Research and Therapy, Vol. 12, No. 1, R29, 18.02.2010.

Research output: Contribution to journalArticle

Adamopoulos, I, Chao, CC, Geissler, R, Laface, D, Blumenschein, W, Iwakura, Y, McClanahan, T & Bowman, EP 2010, 'Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors', Arthritis Research and Therapy, vol. 12, no. 1, R29. https://doi.org/10.1186/ar2936
Adamopoulos, Iannis ; Chao, Cheng chi ; Geissler, Richard ; Laface, Drake ; Blumenschein, Wendy ; Iwakura, Yoichiro ; McClanahan, Terrill ; Bowman, Edward P. / Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors. In: Arthritis Research and Therapy. 2010 ; Vol. 12, No. 1.
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