Expression of transforming growth factor-beta isoforms and their receptorsin chronic tendinosis

Chronic tendon lesions are degenerative conditions and may represent a fail ure to repair or remodel the extracellular matrix after repeated micro-inju ry. Since TGF-beta is strongly associated with tissue repair, we investigat ed the expression of TGF-beta isoforms (beta1, beta2 and beta3) and their 2 signalling receptors (TGF-beta RI and TGF-beta RII) in normal and patholog ical Achilles tendons. In all tissues, all 3 TGF-beta isoforms and the 2 re ceptors were present at sites of blood vessels. Cells in the matrix showed no staining for TGF-beta1 or beta3, while TGF-beta2 was associated with cel ls throughout the normal cadaver tendon. Tissue from tendons with pathologi cal lesions showed an increase in cell numbers and percentage TGF-beta2 exp ression. TGF-beta RII showed a wide distribution in cells throughout the ti ssue sections. As with TGF-beta2, there was an increase in the number of ce lls expressing TGF-beta RII in pathological tissue. TGF-beta RI was restric ted to blood vessels and was absent from the fibrillar matrix. We conclude that despite the presence and upregulation of TGF-beta2, TGF-beta signallin g is not propagated due to the lack of TGF-beta RI. This might explain why chronic tendon lesions fail to resolve and suggests that the addition of ex ogenous TGF-beta will have little effect on chronic tendinopathy.