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Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells
  1. Peggy Jacques1,
  2. Stijn Lambrecht1,
  3. Eveline Verheugen1,
  4. Elin Pauwels2,
  5. George Kollias3,
  6. Maria Armaka3,
  7. Marleen Verhoye4,
  8. Annemie Van der Linden4,
  9. Rik Achten5,
  10. Rik J Lories6,
  11. Dirk Elewaut1
  1. 1Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital, Ghent, Belgium
  2. 2UGCT, Department of Physics and Astronomy, University of Ghent, Ghent, Belgium
  3. 3Alexander Fleming Biomedical Sciences Research Center, Vari, Greece
  4. 4Bio-Imaging Lab, University of Antwerp, Antwerp, Belgium
  5. 5Department of Radiology, University Hospital, Ghent, Belgium
  6. 6Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Center, Department of Development and Regeneration, KU Leuven, Belgium
  1. Correspondence to Dr Peggy Jacques or Dr Dirk Elewaut, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, Department of Rheumatology, De Pintelaan 185, Ghent 9000, Belgium; Peggy.jacques{at}ugent.be or dirk.elewaut{at}ugent.be

Abstract

Objectives Spondyloarthritides (SpA) are characterised by both peripheral and axial arthritis. The hallmarks of peripheral SpA are the development of enthesitis, most typically of the Achilles tendon and plantar fascia, and new bone formation. This study was undertaken to unravel the mechanisms leading towards enthesitis and new bone formation in preclinical models of SpA.

Results First, we demonstrated that TNFΔARE mice show typical inflammatory features highly reminiscent of SpA. The first signs of inflammation were found at the entheses. Importantly, enthesitis occurred equally in the presence or absence of mature T and B cells, underscoring the importance of stromal cells. Hind limb unloading in TNFΔARE mice significantly suppressed inflammation of the Achilles tendon compared with weight bearing controls. Erk1/2 signalling plays a crucial role in mechanotransduction-associated inflammation. Furthermore, new bone formation is strongly promoted at entheseal sites by biomechanical stress and correlates with the degree of inflammation.

Conclusions These findings provide a formal proof of the concept that mechanical strain drives both entheseal inflammation and new bone formation in SpA.

  • Spondyloarthritis
  • Inflammation
  • Fibroblasts

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