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

IE Adamopoulos, C Chao, R Geissler, D Laface… - Arthritis research & …, 2010 - Springer
IE Adamopoulos, C Chao, R Geissler, D Laface, W Blumenschein, Y Iwakura, T McClanahan…
Arthritis research & therapy, 2010Springer
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 …
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.
Springer