The overall incidence of cuff tears increases with age, individuals over 80years having a 51% incidence of a tear. Currently, the aetiology of rotator cuff tears remains unclear and successful repair is achieved in only 30% patients. Matrix metalloproteinases (MMPs) have roles in a wide range of physiological processes including placentation and embryogenesis, tissue remodelling and wound healing. However, the ability of MMPs to dissolve extracellular matrix has been linked to a variety of pathological processes including rheumatoid arthritis, osteoarthritis, periodontitis and multiple sclerosis, which involve excessive matrix destruction. Production of gelatinase MMPs by torn rotator cuff has been demonstrated. The objectives of this study were to examine the expression of MMPs and their association with histological changes in full thickness tears of the rotator cuff.

Rotator cuff tissue was obtained from ten patients (age 40–80years) undergoing surgical repair. The size of tear was 1–4.5cm; time from presentation to surgery was 1 month (acute) to between 0.5–4years (chronic). Immunohistochemical staining with commercial monoclonal antibodies to a range of MMPs, endothelial, macrophage and fibroblast markers was performed. Production of gelatinase MMPs was measured by gelatin zymography on tissue culture supernatant. Visualisation used a standard DAB chromagen technique.

In the acute specimens there was an infiltrate of macrophages with little collagen degeneration; the fibro-blasts were MMP1 positive and endothelial cells MMP2 positive. At 12 months post-tear mature collagen, plump fibroblasts and proliferating endothelial cells were identified adjacent to the resection edge. Towards the torn edge areas of lower cellularity, sparse vascularity and collagen degeneration were observed. Vimentin positive, CD68 negative cells within this matrix were rounded with foamy cytoplasm, and intensely positive for MMP1 and MMP2, and positive for MMP-3, -10, -11, -13 and -14. Tissue culture supernatant demonstrated active and latent MMP2 production in all cases.

The prolonged interval between trauma and surgical repair, with potential pharmacological intervention, remedial physiotherapy and disuse immobility, make assessment of the factors contributing to tendon degeneration difficult to determine. Fatty infiltration, dystrophic calcification and patchy collagen degeneration were common. However, clear evidence of cellular activities typical of wound repair were also identified, including fibroblast and endothelial cell proliferation. The most striking finding was the association between areas of poor collagen structure with fibroblasts staining intensely for both MMP1 and MMP2 and positive for other matrix metalloproteinases. The production of MMP1 and MMP2 may contribute to active remodelling of the tendon matrix. Success of repair could be influenced by both the quality of the matrix and the cell types and activities in the tissue at the resection edge.

Purpose: To investigate the relationships between vascular endothelial growth factor (VEGF), a proliferation marker (Ki-67) and the cell cycle inhibitor p27 (cyclin-dependent kinase inhibitor p27), in endothelial cells in chronic degeneration of the rotator cuff.

Background: The rotator cuff is subject to constant pressure from the head of the humerus. This tends to ‘wring out’ the blood supply resulting in a functionally avascular critical zone, although microvessels can be identified. This zone is the site of degeneration and tears. Attempts at repair under these circumstances could be compromised by inadequate local function of the vascular system particularly sprouting of the capillaries to support the repair process.

Methods: Rotator cuff tissue was obtained from ten patients (age 40–80y) undergoing surgical repair. The size of tear was 1–4.5cm, time from presentation to surgery was 1 month (acute) to between 0.5–4y (chronic). Immunohistochemical staining with commercial mono-clonal antibodies to VEGF, p27, Ki-67 was performed on formalin fixed paraffin embedded tissues. Endothelial cells were identified by CD31 and smooth muscle actin (SMA) positivity. Visualisation used a standard DAB chromagen technique.

Results: Microvessel distribution varied according to tissue location, being pronounced towards the muscle insertion and torn edges of tissue, but much reduced in areas of healthy tendon and absent from areas with clear signs of advanced matrix degeneration without tears. Widespread VEGF positivity was observed in fibroblast and endothelial cell populations and diffusely within the matrix. Strong P27 positivity was observed in many endothelial cells which consequently demonstrated little Ki-67 staining.

Conclusion: Thus the endothelial cells appear to be simultaneously under both a mitogenic, VEGF drive, and subject to an inhibition of proliferation i.e. p27 positivity.