Spontaneous arthritis and ankylosis in male DBA/1 mice: further evidence for a role of behavioral factors in "stress-induced arthritis".

Background: Ageing male DBA/1 mice spontaneously develop arthritis in the hind paws. We and others have demonstrated that this model shares striking features with human spondyloarthritis, in particular entheseal involvement, progressive ankylosis but also dactylitis. Here, we report on our recent experience with this model highlighting how changes in the animal facility affect the development of the disease.

The role of bone morphogenetic proteins in ankylosing spondylitis.

Ankylosing spondylitis (AS), the best-known form of spondyloarthritis (SpA), is a remodelling arthritis characterized by chronic inflammation and bone formation. Ankylosis of the axial skeleton and sacroiliac joints leads to an impairment of spinal mobility, progressive spinal fusion and an increased risk of spinal fractures. The nature of the relationship between inflammation and new bone formation in AS has been controversial and questions remain as to whether there is a direct relationship between inflammation and new bone formation.

Inhibition of inflammation but not ankylosis by glucocorticoids in mice: further evidence for the entheseal stress hypothesis.

Introduction: Studies in the spontaneous ankylosis model in aging male DBA/1 mice and in patients with ankylosing spondylitis provide evidence that inflammation and new tissue formation leading to joint or spine ankylosis are likely linked but largely uncoupled processes. We previously proposed the 'entheseal stress' hypothesis that defines microdamage or cell stress in the enthesis as a trigger for these disease processes. Here, we further investigated the relationship between inflammation and ankylosis by focusing on the early phase of the spontaneous arthritis model.

Blocking p38 signalling inhibits chondrogenesis in vitro but not ankylosis in a model of ankylosing spondylitis in vivo.

Objectives: To investigate p38 mitogen activated protein kinase (MAPK) signalling in an in vitro model of bone morphogenetic protein (BMP) and transforming growth factor β (TGFβ)-induced chondrogenesis and in vivo, with specific attention to its potential role in ankylosing enthesitis.

Methods: Human periosteum-derived cells (hPDCs) were cultured in pellets and stimulated with BMP2 or TGFβ1 in the presence or absence of a p38 inhibitor SB203580 or proinflammatory cytokines. Chondrogenic differentiation was evaluated using quantitative PCR.

Insights into the pathophysiology of ankylosing spondylitis: contributions from animal models.

The introduction of anti-tumor necrosis factor strategies has significantly changed the perspective and outcome of patients with ankylosing spondylitis and related spondyloarthritides. This breakthrough has also boosted further research efforts into the mechanisms of disease. As human tissue specimens of the spine and sacroiliac joints are very difficult to obtain and rarely allow mechanistic studies, most of the new concepts have emerged from different animal models of disease.