Abstract
Introduction: Osteoarthritis (OA) has historically been thought of as a degenerative joint disease, but inflammation and angiogenesis are increasingly being recognised as contributing to the pathogenesis, symptoms and progression of OA. β-dystroglycan (β-DG) is a pivotal element of the transmembrane adhesion molecule involved in cell-extracellular matrix adhesion and angiogenesis. Matrix metalloproteinases (MMPs) are the main enzymes responsible for cartilage extracellular matrix breakdown and are also implicated in both angiogenesis and β-DG degradation in a number of malignancies. We aimed to investigate the expression and localisation of β-DG and MMP-3, -9, and -13 within cartilage, synovium and synovial fluid and establish their roles in the pathogenesis of OA.
Methods: Following ethical committee approval, cartilage, synovium and synovial fluid were obtained from the hip joints of 5 osteoarthritic (patients undergoing total hip replacement) and 5 control hip joints (patients undergoing hemiarthroplasty for femoral neck fracture). The samples were analysed for β-DG expression using Western Blotting and for the distribution of β-DG, MMP-3, -9, and -13 using immunohistochemistry on paraffin embedded tissue.
Results: Whilst no significant expression of β-DG was found in cartilage or synovial fluid, β-DG was expressed in the smooth muscle of both normal and osteoarthritic synovial blood vessels. Moreover, β-DG was expressed in endothelium of blood vessels of OA synovium, but not in the normal endothelium. In the endothelium of osteoarthritic synovial blood vessels, β-DG co-localised with MMP −3 and −9.
Discussion: Our results demonstrate that β-DG does not act as a cell adhesion molecule binding chondrocytes to the ECM. However, specific immunolocalisation of β-DG within endothelium of inflamed OA blood vessels suggests that β-DG may play a role in angiogenesis associated with OA. Its co-localisation with MMP-3 and −9, previously reported to also have pro-angiogenic roles, may be linked. Further research is required to understand these roles more fully.
Correspondence should be addressed to The Secretary, BHS, c/o BOA, The Royal College of Surgeons, 35–43 Lincoln’s Inn Fields, London WC2A 3PE.