Proof of concept : enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells
| Autor: | Stijn Lambrecht, Annemie Van der Linden, Elin Pauwels, Rik Achten, Maria Armaka, Peggy Jacques, Marleen Verhoye, Rik Lories, George Kollias, Eveline Verheugen, Dirk Elewaut |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
musculoskeletal diseases
Pathology medicine.medical_specialty Stromal cell MAP Kinase Signaling System T-Lymphocytes Immunology Arthritis Inflammation Achilles Tendon Mechanotransduction Cellular General Biochemistry Genetics and Molecular Biology Weight-Bearing Mice Rheumatology Osteogenesis Spondylarthritis medicine Immunology and Allergy Animals Sacroiliitis Biology Ankylosing spondylitis Achilles tendon B-Lymphocytes business.industry Tumor Necrosis Factor-alpha Enthesitis X-Ray Microtomography medicine.disease Enthesis Arthritis Experimental Magnetic Resonance Imaging medicine.anatomical_structure Rheumatoid arthritis Tendinopathy Stress Mechanical Human medicine medicine.symptom Stromal Cells business |
| Zdroj: | Annals of the rheumatic diseases |
| ISSN: | 0003-4967 |
| Popis: | 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 TNF ΔARE 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 TNF ΔARE 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. |
| Databáze: | OpenAIRE |
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