Actions of SPM in Regulating Host Responses in Arthritis

The discovery and identification of omega-3 fatty acid derived specialized pro-resolving mediators (SPM) provides a molecular mechanism for the beneficial effects of fish oil supplementation in patients suffering from arthritis. Here we review the plethora of bioactions of SPM in the context of joint diseases, focusing on both cellular targets and molecular mechanisms. Whenever possible, a parallel to clinical and preclinical data produced with fish oil supplementation is made to strengthen the mechanistic link between omega-3 fatty acids and SPM biosynthesis. SPM can modulate the reactivity of many cells that are pivotal to the development and/or maintenance of joint disease. Whereas work has so far focused on the actions of SPM on immune cells and therefore, within this context, macrophages, neutrophils, mast cells and T cells, we reason that more work needs to focus on the effects that these bioactive lipid mediators may have on the structural cell component of the joint, this encompassing synovial fibroblasts, chondrocytes, osteoclasts and osteoblasts. Full definition of the properties that SPM may exert on these cells can help in unveiling their ability to promote tissue restoration and regeneration, a prerequisite to repair joint damage, and as such promote the development of innovative therapeutic strategies based on the science of SPM and resolution.