TY - JOUR T1 - Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 437 LP - 445 DO - 10.1136/annrheumdis-2013-203643 VL - 73 IS - 2 AU - Peggy Jacques AU - Stijn Lambrecht AU - Eveline Verheugen AU - Elin Pauwels AU - George Kollias AU - Maria Armaka AU - Marleen Verhoye AU - Annemie Van der Linden AU - Rik Achten AU - Rik J Lories AU - Dirk Elewaut Y1 - 2014/02/01 UR - http://ard.bmj.com/content/73/2/437.abstract N2 - 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. ER -