Expression of transforming growth factor‐beta isoforms and their receptors in chronic tendinosis

Abstract

Chronic tendon lesions are degenerative conditions and may represent a failure to repair or remodel the extracellular matrix after repeated micro-injury. Since TGF-β is strongly associated with tissue repair, we investigated the expression of TGF-β isoforms ( β1, β2 and β3) and their 2 signalling receptors (TGF-βRI and TGF-βRII) in normal and pathological Achilles tendons. In all tissues, all 3 TGF-β isoforms and the 2 receptors were present at sites of blood vessels. Cells in the matrix showed no staining for TGF-β1 or β3, while TGF-β2 was associated with cells throughout the normal cadaver tendon. Tissue from tendons with pathological lesions showed an increase in cell numbers and percentage TGF-β2 expression. TGF-βRII showed a wide distribution in cells throughout the tissue sections. As with TGF-β2, there was an increase in the number of cells expressing TGF-βRII in pathological tissue. TGF-βRI was restricted to blood vessels and was absent from the fibrillar matrix. We conclude that despite the presence and upregulation of TGF-β2, TGF-β signalling is not propagated due to the lack of TGF-βRI. This might explain why chronic tendon lesions fail to resolve and suggests that the addition of exogenous TGF-β will have little effect on chronic tendinopathy.

Spatiotemporal protein distribution of TGF‐βs, their receptors, and extracellular matrix molecules during embryonic tendon development

“…By day 16, all three isoforms and their receptors are strongly detected along with fibronectin. In normal and pathological Achilles tendons, TGF-␤s and RI and RII are expressed at sites of vascularization (Fenwick et al, 2001). VEGF is expressed during development in both tertiary bundles as well as in the endotenon (unpublished data).…”

“…In contrast, most studies have focused mainly on the role of TGF-␤s in adult tendon and ligament pathology and wound healing. Thus, elevated protein and mRNA levels of TGF-␤ have been demonstrated in pathological Achilles tendons and during healing of injured tendons and ligaments (Natsu-ume et al, 1997;Fenwick et al, 2001;Darmani et al, 2004;Tsubone et al, 2004;Dahlgren et al, 2005). Exogenous application of TGF-␤1 and -␤2 significantly increased expression of collagen types I and III, and improved the mechanical properties of healing tendons or ligaments (Spindler et al, 2003;Kashiwagi et al, 2004;Anaguchi et al, 2005).…”

Tendinopathy—from basic science to treatment

“…48 The expression of growth factors and other potential modulators of tendon cell activity has been shown to increase in tendino pathy, including transforming growth factor β, platelet-derived growth factor receptor and neuro transmitters, such as glutamate and substance P. 42,47,[49][50][51] These changes might, however, be part of the healing response of the tissue and a requisite for tendon repair. 52,53 …”

Work-Related Musculoskeletal Disorders of the Hand and Wrist: Epidemiology, Pathophysiology, and Sensorimotor Changes

“…Human studies examining tendon and sheath biopsies collected from patients with chronic tendinopathies or CTS (Table 4) find marked tendon and sheath degeneration and fibrosis in combination with inflammatory or proliferative changes. 8,29,47,51,88 In animal models, marked tendon injury is dependent on force, frequency, and duration of repetitive exposure (Table 3). Tendon necrosis and matrix disorganization are found only in studies utilizing intensive repetitive kicking or intensive running combined with tendon compression.…”