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Arthritis Res Ther. 2010;12(1):R29. doi: 10.1186/ar2936. Epub 2010 Feb 18.

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

Author information

1
Discovery Research, Schering-Plough Biopharma (formerly DNAX Research, Inc,), 901 South California Avenue, Palo Alto, CA 94304, USA. iannis.adamopoulos@spcorp.com

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-kappaB 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-kappaB 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.

PMID:
20167120
PMCID:
PMC2875663
DOI:
10.1186/ar2936
[Indexed for MEDLINE]
Free PMC Article

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