Chronic tendon pathology: molecular basis and therapeutic implications

Abstract

Tendons are frequently affected by chronic pain or rupture. Many causative factors have been implicated in the pathology, which until relatively recently was under-researched and poorly understood. There is now a greater knowledge of the molecular basis of tendon disease. Most tendon pathology (tendinopathy) is associated with degeneration, which is thought to be an active, cell-mediated process involving increased turnover and remodelling of the tendon extracellular matrix. Degradation of the tendon matrix is mediated by a variety of metalloproteinase enzymes, including matrix metalloproteinases and 'aggrecanases'. Neuropeptides and other factors released by stimulated cells or nerve endings in or around the tendon might influence matrix turnover, and could provide novel targets for therapeutic intervention.Tendons are dense, fibrous connective tissues that connect muscle to bone and are essential for the transmission of force and the generation of movement at a joint. They are highly ordered composite materials consisting of collagens, proteoglycans and various glycoproteins, many of which have been poorly characterised. Tendon problems such as tendon rupture and chronic tendon pain are common, although the underlying pathology is not well understood and the conditions are often difficult to treat (Ref.

Chondrocyte Phenotype and Ectopic Ossification in Collagenase-induced Tendon Degeneration

“…Our results showed that collagenase injection exhibited many key features of tendinopathy including hypercellularity, loss of matrix organization, increased vascularity, and absence of infiltration of inflammatory cells as reported in previous studies (Jarvinen et al 1997;Khan et al 1999;Riley 2005;Fu et al 2002aFu et al , b,2007. The patellar tendon failed to heal histologically by the end of week 32.…”

What We Should Know Before Using Tissue Engineering Techniques to Repair Injured Tendons: A Developmental Biology Perspective

“…13 Most tendon injuries involve a degenerative component that can take years to develop. 71,72 Tendon degeneration, or tendinosis, can lead to matrix disorganization, mucoid degeneration, and fatty infiltration. [73][74][75][76] The hypovascular and bFGF, basic fibroblast growth factor; ACL, anterior cruciate ligament; MCL, medial collateral ligament; PT, patellar tendon; GDF, growth and differentiation factor; IGF, insulin-like growth factor; MSC, mesenchymal stem cell; TGFb, transforming growth factor b; PDGF, plateletderived growth factor; VEGF, vascular endothelial growth factor; SDF-1, stromal cell-derived factor-1.…”

Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain

“…There is an emerging hypothesis that excessive mechanical strain on tendons modulates the metabolism and/or phenotype of the resident tenocytes, disrupting the balance of matrix synthesis and degradation (for review, see ref. 15). Partial tendon tearing then occurs through abnormal tissue, and this results in increased strain on the remaining tendon and further deterioration.…”