Expression of transforming growth factor-beta isoforms and their receptors in chronic tendinosis.
Chronic tendon lesions are degenerative conditions and may represent a failure to repair or remodel the extracellular matrix after repeated micro-injury. Since TGF-beta is strongly associated with tissue repair, we investigated the expression of TGF-beta isoforms (beta1, beta2 and beta3) and their 2 signalling receptors (TGF-betaRI and TGF-betaRII) in normal and pathological Achilles tendons. In all tissues, all 3 TGF-beta isoforms and the 2 receptors 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 cells throughout the normal cadaver tendon. Tissue from tendons with pathological lesions showed an increase in cell numbers and percentage TGF-beta2 expression. TGF-betaRII showed a wide distribution in cells throughout the tissue sections. As with TGF-beta2, there was an increase in the number of cells expressing TGF-betaRII in pathological tissue. TGF-betaRI was restricted to blood vessels and was absent from the fibrillar matrix. We conclude that despite the presence and upregulation of TGF-beta2, TGF-beta signalling is not propagated due to the lack of TGF-betaRI. This might explain why chronic tendon lesions fail to resolve and suggests that the addition of exogenous TGF-beta will have little effect on chronic tendinopathy.
Fenwick
S A
SA
Rheumatology Research Unit, Addenbrookes Hospital, Cambridge, UK.
Curry
V
V
Harrall
R L
RL
Hazleman
B L
BL
Hackney
R
R
Riley
G P
GP
D000125:Achilles Tendon / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta