Rheumatoid cachexia: the underappreciated role of myoblast, macrophage and fibroblast interplay in the skeletal muscle niche

Abstract

AbstractAlthough rheumatoid arthritis affects 1% of the global population, the role of rheumatoid cachexia, which occurs in up to a third of patients, is relatively neglected as research focus, despite its significant contribution to decreased quality of life in patients. A better understanding of the cellular and molecular processes involved in rheumatoid cachexia, as well as its potential treatment, is dependent on elucidation of the intricate interactions of the cells involved, such as myoblasts, fibroblasts and macrophages. Persistent RA-associated inflammation results in a relative depletion of the capacity for regeneration and repair in the satellite cell niche. The repair that does proceed is suboptimal due to dysregulated communication from the other cellular role players in this multi-cellular environment. This includes the incomplete switch in macrophage phenotype resulting in a lingering pro-inflammatory state within the tissues, as well as fibroblast-associated dysregulation of the dynamic control of the extracellular matrix. Additional to this endogenous dysregulation, some treatment strategies for RA may exacerbate muscle wasting and no multi-cell investigation has been done in this context. This review summarizes the most recent literature characterising clinical RA cachexia and links these features to the roles of and complex communication between multiple cellular contributors in the muscle niche, highlighting the importance of a targeted approach to therapeutic intervention.