Erroneous Differentiation of Tendon Stem/Progenitor Cells in the Pathogenesis of Tendinopathy: Current Evidence and Future Perspectives.

Tendinopathy is a condition characterized by persistent tendon pain, structural damage, and compromised functionality. Presently, the treatment for tendinopathy remains a formidable challenge, partly because of its unclear pathogenesis. Tendon stem/progenitor cells (TSPCs) are essential for tendon homeostasis, regeneration, remodeling, and repair. An innovative theory has been previously proposed, with insufficient evidence, that the erroneous differentiation of TSPCs may constitute one of the fundamental mechanisms underpinning tendinopathy. Over the past few years, there has been accumulating evidence for plausibility of this theory. In this review, we delve into alterations in the differentiation potential of TSPCs and the underlying mechanisms in the context of injury-induced tendinopathy, diabetic tendinopathy, and age-related tendinopathy to provide updated evidence on the erroneous differentiation theory. Despite certain limitations inherent in the existing body of evidence, the erroneous differentiation theory emerges as a promising and highly pertinent avenue for understanding tendinopathy. In the future, advanced methodologies will be harnessed to further deepen comprehension of this theory, paving the way for prospective developments in clinical therapies targeting TSPCs for the management of tendinopathy.