Tenocytes from Ruptured and Tendinopathic Achilles Tendons Produce Greater Quantities of Type III Collagen than Tenocytes from Normal Achilles Tendons: An in Vitro Model of Human Tendon Healing

Abstract

Type I collagen is the main collagen in tendons; type III collagen is present in small amounts. Ruptured Achilles tendons contain a significantly greater proportion of type Ill collagen, which predisposes them to rupture. We used an in vitro model to determine whether tenocytes from Achilles tendons that were ruptured (N = 22), nonruptured (N = 7), tendinopathic (N = 12), and fetal (N = 8) show different behavior. Samples of Achilles tendon were digested with collagenase and the released tenocytes were collected. Primary tenocyte cultures were established and subsequently cultured onto glass coverslips. Once a confluent monolayer was obtained, the cell populations were "wounded" by scraping a pipette tip along the surface. The cultures were further incubated for either 1, 4, 8, 12, 16, or 24 hours, and production of types I and II collagen was assessed by immunostaining. In cultures from ruptured and tendinopathic tendons, there was increased production of type Ill collagen. Athletic participation places excess stress on the Achilles tendon, which could potentially lead to areas of microtrauma within the tendon. These areas may heal by the production of type III collagen, which is an abnormal healing response. Accumulation of such episodes of microtrauma could resuit in a critical point where the resistance of the tissue to tensile forces is compromised and tendon rupture occurs.

Tenocyte responses to mechanical loading in vivo: A role for local insulin‐like growth factor 1 signaling in early tendinosis in rats

“…Transforming growth factor ␤1, platelet-derived growth factor receptor ␤, and IGF-1 are all reported to be up-regulated in tendinosis biopsy samples, even in the chronic stage (months after loading has been discontinued) (36)(37)(38). Although the current study suggests that the stimulus for tenocyte proliferation may be driven locally by load-induced proliferation, in chronic stages other factors, such as hypoxia or transformation to a fibrotic phenotype, may play a role in persistent growth factor up-regulation and proliferation (21,(39)(40)(41).…”

The Basic Science of Tendinopathy

“…Tenocytes from the site of tendinopathy also produce abnormal amounts of collagen III, commonly associated with wound healing, even when the repetitive motion is no longer present [69].…”

Movin and Bonar Scores Assess the Same Characteristics of Tendon Histology

“…Over the last decade, several studies have provided the opportunity to develop novel therapeutic strategies [4-9, 17, 19, 23, 26]. While many of the epidemiological and imaging difficulties have been addressed [2,11], relatively few studies have tried to quantify the histopathological findings of tendinopathy [18,20,21], and the histopathological changes are currently described in a subjective or at best semiquantitative fashion [1,12,20,25,27]. This may result in uncertainty about the histopathological findings of tendinopathy, and has produced a lack of diagnostic uniformity among surgical pathologists.…”