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 language | English (US) |
|---|---|
| Article number | R29 |
| Journal | Arthritis Research and Therapy |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 18 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Rheumatology
- Immunology
- Immunology and Allergy
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors
AU - Adamopoulos, Iannis
AU - Chao, Cheng chi
AU - Geissler, Richard
AU - Laface, Drake
AU - Blumenschein, Wendy
AU - Iwakura, Yoichiro
AU - McClanahan, Terrill
AU - Bowman, Edward P.
PY - 2010/2/18
Y1 - 2010/2/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77949454280&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949454280&partnerID=8YFLogxK
U2 - 10.1186/ar2936
DO - 10.1186/ar2936
M3 - Article
C2 - 20167120
AN - SCOPUS:77949454280
VL - 12
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
SN - 1478-6354
IS - 1
M1 - R29
ER -