Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells

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 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.

Analysis of Bone Samples from Patients with Spondyloarthritides—Identifying Causes of New Bone Formation in Axial Spondyloarthritis

“…This subject cannot be discussed in detail at this point, but the results from DBA/1 mice that develop arthritis and enthesial ankylosis have led to new insights into molecular pathways 19 , which might also be involved in disease progression in patients with AS. This work and the recently published analysis of TNFΔARE mice 20 in which typical inflammatory lesions similar to SpA as well as new bone formation were observed -both induced through mechanical stress -give evidence that new bone formation can also be driven by mechanical stress in this animal model. Third, inflammation and new bone formation in bony tissue samples from patients with SpA have been analyzed histomorphologically and immunohistochemically.…”

Evaluation of the health care budget impact of secukinumab treatment in patients with ankylosing spondylitis

“…Кроме того, при изолиро-ванной гиперэкспрессии данного цитокина у лабораторных мышей развивались специфические проявления АС. Пока-зана также высокая эффективность применения монокло-нальных антител к ФНОα при АС [3][4][5]. Однако последние исследования генома установили, что в патогенез АС вовле-чено множество иммунных сигнальных путей: путь интер-лейкина (ИЛ)17/ИЛ23, cигнальные пути ядерного транс-крипционного фактора NF-kB, антигены, регулирующие главный комплекс гистосовместимости, а также другие ге-ны, контролирующие субпопуляции Т-лимфоцитов CD8 и CD4 [6,7].…”

Enthesitis of the hands in psoriatic arthritis: an ultrasonographic perspective

“…tendons, entheses, and bursae) and enthesitis seems to be the earliest lesion in animal models of SpA [1,2]. From a clinical point of view, in 1971 Ball et al firstly described enthesitis in SpA [3].…”