Tendinopathy: The Interplay between Mechanical Stress, Inflammation, and Vascularity

Tendinopathy is a long-lasting, debilitating disease that not only affects patients' individual lives, but also imposes a significant socioeconomic burden. Due to an insufficient understanding of the underlying pathomechanisms, treatment options remain limited. Although tendinopathy is recognized as a multifactorial disorder, known risk factors and predisposing conditions have largely been studied in isolation. In this review, it is aimed to examine the various pathomechanisms identified to date and synthesize them into a unified concept. Particular emphasis is placed on key drivers believed to be critical in the onset and progression of the disease-namely mechanical stress, inflammation, and vascular changes. By exploring molecular signaling pathways and conditions involved in tendinopathy, how these mechanisms interact and reinforce one another is illustrated, forming a complex and dynamic signaling network, referred to as the tendinopathic loop. In the future, this network is expected to become even more intricate with the inclusion of emerging concepts such as intratendinous pressure and the potential influence of metabolic factors.