R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway

Krönke G, Uderhardt S, Kim KA, Stock M, Scholtysek C, Zaiss M, Surmann-Schmitt C, Luther J, Katzenbeisser J, David JP, Abdollahi-Roodsaz S, Tran K, Bright JM, Binnerts ME, Akhmetshina A, Böhm C, Distler J, Joosten LAB, Schett G, Abo A (2010)

Publication Type: Journal article

Publication year: 2010

Journal

Arthritis and Rheumatism Wiley

Book Volume: 62

Pages Range: 2303-2312

Journal Issue: 8

DOI: 10.1002/art.27496

Abstract

Objective. During the course of different musculoskeletal diseases, joints are progressively damaged by inflammatory, infectious, or mechanical stressors, leading to joint destruction and disability. While effective strategies to inhibit joint inflammation, such as targeted cytokine-blocking therapy, have been developed during the last decade, the molecular mechanisms of joint damage are still poorly understood. This study was undertaken to investigate the role of the Wnt pathway modulator R-Spondin 1 (RSpo1) in protecting bone and cartilage in a mouse model of arthritis. Methods. Tumor necrosis factor α (TNFα)-transgenic mice were treated with vehicle or Rspo1. Mice were evaluated for signs of arthritis, and histologic analysis of the hind paws was performed. Moreover, we determined the effect of Rspo1 on Wnt signaling activity and osteoprotegerin (OPG) expression in murine primary osteoblasts. Results. The secreted Wnt pathway modulator RSpo1 was highly effective in preserving the structural integrity of joints in a TNFα-transgenic mouse model of arthritis by protecting bone and cartilage from inflammation-related damage. RSpo1 antagonized the Wnt inhibitor Dkk-1 and modulated Wnt signaling in mouse mesenchymal cells. In osteoblasts, RSpo1 induced differentiation and expression of OPG, thereby inhibiting osteoclastogenesis in vitro. In vivo, RSpo1 promoted osteoblast differentiation and bone formation while blocking osteoclast development, thereby contributing to the integrity of joints during inflammatory arthritis. Conclusion. Our results demonstrate the therapeutic potential of RSpo1 as an anabolic agent for the preservation of joint architecture. © 2010, American College of Rheumatology.

Authors with CRIS profile

Gerhard Krönke Department of Medicine 3 – Rheumatology and Immunology Stefan Uderhardt Department of Medicine 3 – Rheumatology and Immunology Michael Stock Department of Medicine 3 – Rheumatology and Immunology Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology Christina Böhm Department of Medicine 3 – Rheumatology and Immunology Jörg Distler Professur für Molekulare Mechanismen der Organfibrose Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

Radboud University Nijmegen NL Netherlands (NL) Nuvelo Inc US United States (USA) (US)

How to cite

APA:

Krönke, G., Uderhardt, S., Kim, K.-A., Stock, M., Scholtysek, C., Zaiss, M.,... Abo, A. (2010). R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway. Arthritis and Rheumatism, 62(8), 2303-2312. https://doi.org/10.1002/art.27496

MLA:

Krönke, Gerhard, et al. "R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway." Arthritis and Rheumatism 62.8 (2010): 2303-2312.

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