Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells.
OBJECTIVE
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.
Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, University Hospital, , Ghent, Belgium.
Peggy
P
Jacques
Stijn
S
Lambrecht
Eveline
E
Verheugen
Elin
E
Pauwels
George
G
Kollias
Maria
M
Armaka
Marleen
M
Verhoye
Annemie
A
Van der Linden
Rik
R
Achten
Rik J
RJ
Lories
Dirk
D
Elewaut
D000125:Achilles Tendon / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001402:B-Lymphocytes / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008279:Magnetic Resonance Imaging; D040542:Mechanotransduction, Cellular / Q000502:physiology; D051379:Mice; D010012:Osteogenesis / Q000502:physiology*; D058566:Sacroiliitis / Q000209:etiology / Q000473:pathology; D025241:Spondylarthritis / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013314:Stress, Mechanical; D017154:Stromal Cells / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D052256:Tendinopathy / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D016474:Weight-Bearing / Q000502:physiology; D055114:X-Ray Microtomography
D014409:Tumor Necrosis Factor-alpha
Fibroblasts; Inflammation; Spondyloarthritis