Rsk2 controls synovial fibroblast hyperplasia and the course of arthritis

Derer A, Boehm C, Groetsch B, Gruen JR, Gruetzkau A, Stock M, Böhm S, Sehnert B, Gaipl U, Schett G, Hueber A, David JP (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 75

Pages Range: 413-21

Journal Issue: 2

DOI: 10.1136/annrheumdis-2014-205618

Abstract

Arthritis is a chronic inflammatory disease characterised by immune cell infiltration and mesenchymal cell expansion in the joints. Although the role of immune cells in arthritis is well characterised, the development of mesenchymal cell hyperplasia needs to be better defined. Here, we analysed the role of the ribosomal S6 kinase Rsk2, which we found to be highly activated in joints of patients with arthritis, in the development of mesenchymal cell hyperplasia.We genetically inactivated Rsk2 in the tumour necrosis factor (TNF)-? transgenic (TNFtg) mice, an animal model for human inflammatory arthritis. Clinical and histological signs of arthritis as well as molecular markers of inflammation and joint destruction were quantified. Fibroblast-like synoviocytes (FLS) were characterised in vitro and the effect of Rsk2 deletion on the pattern of gene expression was determined.Rsk2 deficiency in TNFtg mice results in earlier and exacerbated inflammation as well as increased bone and cartilage destruction. The production of inflammatory cytokines, matrix metalloproteinases and osteoclastogenic molecules was significantly increased in vivo upon Rsk2 inactivation. Bone marrow deficient in Rsk2 could not transfer this phenotype, indicating that Rsk2 expression in mesenchymal cells controls the course of arthritis. Indeed, Rsk2 deficiency was associated with a more activated phenotype and higher proliferative capacity of FLS, thereby increasing cytokines and production of matrix proteinases.Rsk2 emerges as a key regulator of mesenchymal cell numbers in the joint and thereby could be targeted to control the inflammatory and tissue-destructive feature of joints in arthritis.

Authors with CRIS profile

Involved external institutions

Deutsches Rheuma-Forschungszentrum (DRFZ) Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE)

How to cite

APA:

Derer, A., Boehm, C., Groetsch, B., Gruen, J.R., Gruetzkau, A., Stock, M.,... David, J.-P. (2016). Rsk2 controls synovial fibroblast hyperplasia and the course of arthritis. Annals of the Rheumatic Diseases, 75(2), 413-21. https://dx.doi.org/10.1136/annrheumdis-2014-205618

MLA:

Derer, Anja, et al. "Rsk2 controls synovial fibroblast hyperplasia and the course of arthritis." Annals of the Rheumatic Diseases 75.2 (2016): 413-21.

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