Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF-driven spondyloarthritis.

Objectives: Gut and joint inflammation commonly co-occur in spondyloarthritis (SpA) which strongly restricts therapeutic modalities. The immunobiology underlying differences between gut and joint immune regulation, however, is poorly understood. We therefore assessed the immunoregulatory role of CD4FOXP3 regulatory T (Treg) cells in a model of Crohn's-like ileitis and concomitant arthritis.

ELMO1 signaling is a promoter of osteoclast function and bone loss.

Osteoporosis affects millions worldwide and is often caused by osteoclast induced bone loss. Here, we identify the cytoplasmic protein ELMO1 as an important 'signaling node' in osteoclasts. We note that ELMO1 SNPs associate with bone abnormalities in humans, and that ELMO1 deletion in mice reduces bone loss in four in vivo models: osteoprotegerin deficiency, ovariectomy, and two types of inflammatory arthritis.

Tendon and ligament mechanical loading in the pathogenesis of inflammatory arthritis.

Mechanical loading is an important factor in musculoskeletal health and disease. Tendons and ligaments require physiological levels of mechanical loading to develop and maintain their tissue architecture, a process that is achieved at the cellular level through mechanotransduction-mediated fine tuning of the extracellular matrix by tendon and ligament stromal cells. Pathological levels of force represent a biological (mechanical) stress that elicits an immune system-mediated tissue repair pathway in tendons and ligaments.

Running promotes chronicity of arthritis by local modulation of complement activators and impairing T regulatory feedback loops.

Objectives: The mechanisms driving onset of joint inflammation in arthritides such as rheumatoid arthritis and spondyloarthritis and the conversion to disease chronicity are poorly understood. We hypothesised mechanostrain could play an instrumental role herein by engaging local and/or systemic pathways, thereby attenuating disease course and outcome.

Methods: The development of collagen antibody-induced arthritis (CAIA) in C57BL/6 mice was evaluated both clinically and histologically under different loading regimens: control, voluntary running or hindpaw unloading.

Born to run: The paradox of biomechanical force in spondyloarthritis from an evolutionary perspective.

Spondyloarthritis (SpA) refers to a group of chronic inflammatory arthritic diseases that can be severely debilitating. The most common form of SpA affecting the peripheral skeleton is psoriatic arthritis, while that affecting the axial skeleton is ankylosing spondylitis. SpA has a multifactorial nature, with both genetic and environmental factors initiating and maintaining the disease.