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Extended report
Rsk2 controls synovial fibroblast hyperplasia and the course of arthritis
  1. Anja Derer1,2,
  2. Christina Böhm1,
  3. Bettina Grötsch1,
  4. Joachim R Grün3,
  5. Andreas Grützkau3,
  6. Michael Stock1,
  7. Sybille Böhm4,
  8. Bettina Sehnert,
  9. Udo Gaipl2,
  10. Georg Schett1,
  11. Axel J Hueber1,
  12. Jean-Pierre David1,5
  1. 1Department of Internal Medicine 3, Rheumatology and Immunology, University of Erlangen-Nuremberg, Erlangen, Germany
  2. 2Department of Radiation Oncology, University of Erlangen-Nuremberg, Erlangen, Germany
  3. 3Regine von Ramin Laboratory for Molecular Rheumatology, German Rheumatism Research Center Berlin (DRFZ), An institute of the Leibniz association, Berlin, Germany
  4. 4Department of Biology, Institute of Genetics, University of Erlangen-Nuremberg, Erlangen, Germany
  5. 5Group Transcription and Gene Expression, Institute of Osteology and Biomechanics (IOBM) University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  1. Correspondence to Dr Jean-Pierre David: Group Transcription and Gene Expression, Institute of Osteology and Biomechanics (IOBM) University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg D20246, Germany; jdavid{at}


Objective 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.

Methods We genetically inactivated Rsk2 in the tumour necrosis factor (TNF)-α 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.

Results 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.

Conclusions 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.

  • Synovitis
  • TNF-alpha
  • Rheumatoid Arthritis
  • Cytokines
  • Bone Mineral Density

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