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

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R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway. / Krönke, Gerhard; Uderhardt, Stefan; Kim, Kyung-Ah; Stock, Michael; Scholtysek, Carina; Zaiss, Mario M; Surmann-Schmitt, Cordula; Luther, Julia; Katzenbeisser, Julia; David, Jean-Pierre; Abdollahi-Roodsaz, Shahla; Tran, Karolyn; Bright, Jessica M; Binnerts, Minke E; Akhmetshina, Alfiya; Böhm, Christina; Distler, Jörg H; Joosten, Leo A B; Schett, Georg; Abo, Arie.

In: ARTHRITIS RHEUMATOL, Vol. 62, No. 8, 01.08.2010, p. 2303-12.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Krönke, G, Uderhardt, S, Kim, K-A, Stock, M, Scholtysek, C, Zaiss, MM, Surmann-Schmitt, C, Luther, J, Katzenbeisser, J, David, J-P, Abdollahi-Roodsaz, S, Tran, K, Bright, JM, Binnerts, ME, Akhmetshina, A, Böhm, C, Distler, JH, Joosten, LAB, Schett, G & Abo, A 2010, 'R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway', ARTHRITIS RHEUMATOL, vol. 62, no. 8, pp. 2303-12. https://doi.org/10.1002/art.27496

APA

Krönke, G., Uderhardt, S., Kim, K-A., Stock, M., Scholtysek, C., Zaiss, M. M., Surmann-Schmitt, C., Luther, J., Katzenbeisser, J., David, J-P., Abdollahi-Roodsaz, S., Tran, K., Bright, J. M., Binnerts, M. E., Akhmetshina, A., Böhm, C., Distler, J. H., Joosten, L. A. B., Schett, G., & Abo, A. (2010). R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway. ARTHRITIS RHEUMATOL, 62(8), 2303-12. https://doi.org/10.1002/art.27496

Vancouver

Krönke G, Uderhardt S, Kim K-A, Stock M, Scholtysek C, Zaiss MM et al. R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway. ARTHRITIS RHEUMATOL. 2010 Aug 1;62(8):2303-12. https://doi.org/10.1002/art.27496

Bibtex

@article{5ed53cb3556341f997662aef4b53fcc3,
title = "R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway",
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 alpha (TNFalpha)-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 TNFalpha-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.",
keywords = "Animals, Arthritis, Experimental, Blotting, Western, Bone and Bones, Cartilage, Fluorescent Antibody Technique, In Situ Hybridization, Inflammation, Mice, Mice, Transgenic, Osteoblasts, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Thrombospondins, Tumor Necrosis Factor-alpha, Wnt Proteins",
author = "Gerhard Kr{\"o}nke and Stefan Uderhardt and Kyung-Ah Kim and Michael Stock and Carina Scholtysek and Zaiss, {Mario M} and Cordula Surmann-Schmitt and Julia Luther and Julia Katzenbeisser and Jean-Pierre David and Shahla Abdollahi-Roodsaz and Karolyn Tran and Bright, {Jessica M} and Binnerts, {Minke E} and Alfiya Akhmetshina and Christina B{\"o}hm and Distler, {J{\"o}rg H} and Joosten, {Leo A B} and Georg Schett and Arie Abo",
year = "2010",
month = aug,
day = "1",
doi = "10.1002/art.27496",
language = "English",
volume = "62",
pages = "2303--12",
journal = "ARTHRITIS RHEUMATOL",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "8",

}

RIS

TY - JOUR

T1 - R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway

AU - Krönke, Gerhard

AU - Uderhardt, Stefan

AU - Kim, Kyung-Ah

AU - Stock, Michael

AU - Scholtysek, Carina

AU - Zaiss, Mario M

AU - Surmann-Schmitt, Cordula

AU - Luther, Julia

AU - Katzenbeisser, Julia

AU - David, Jean-Pierre

AU - Abdollahi-Roodsaz, Shahla

AU - Tran, Karolyn

AU - Bright, Jessica M

AU - Binnerts, Minke E

AU - Akhmetshina, Alfiya

AU - Böhm, Christina

AU - Distler, Jörg H

AU - Joosten, Leo A B

AU - Schett, Georg

AU - Abo, Arie

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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 alpha (TNFalpha)-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 TNFalpha-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.

AB - 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 alpha (TNFalpha)-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 TNFalpha-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.

KW - Animals

KW - Arthritis, Experimental

KW - Blotting, Western

KW - Bone and Bones

KW - Cartilage

KW - Fluorescent Antibody Technique

KW - In Situ Hybridization

KW - Inflammation

KW - Mice

KW - Mice, Transgenic

KW - Osteoblasts

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

KW - Thrombospondins

KW - Tumor Necrosis Factor-alpha

KW - Wnt Proteins

U2 - 10.1002/art.27496

DO - 10.1002/art.27496

M3 - SCORING: Journal article

C2 - 20506554

VL - 62

SP - 2303

EP - 2312

JO - ARTHRITIS RHEUMATOL

JF - ARTHRITIS RHEUMATOL

SN - 2326-5191

IS - 8

ER -