Alarmins in tendinopathy: unravelling new mechanisms in a common disease

Tendon disorders-tendinopathies-are the primary reason for musculoskeletal consultation in primary care in the UK and account for up to 30% of rheumatological consultations. While the molecular pathophysiology of tendinopathy remains incompletely understood, recent observations concerning repetitive stress and cellular load provide important mechanistic insight implicating a role for tissue alarmins. These in turn have an emerging effector role in many disease processes across the rheumatological diseases. Intracellular alarmins, also called damage-associated molecular patterns, are rapidly released following non-programmed cell death, are key effectors of the innate immune system and critically restore homeostasis by promoting the reconstruction of the affected tissue. Recent investigations have highlighted a key role for several alarmins including hypoxia-induced elements, cytokines and heat shock proteins affecting tissue rescue mechanisms in tendon pathology. This review aims to provide an overview of the biology of alarmins in the context of inflammatory mediators and matrix regulation in tendinopathy.