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. b-dystroglycan (b-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 b-DG degradation in a number of malignancies. We aimed to investigate the expression and localisation of b-DG and MMP-3, -9, and -13 within cartilage, synovium and synovial fluid and establish their roles in the pathogenesis of OA.

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.

Introduction: Osteoarthritis has historically been thought of as a degenerative joint disease, but inflam-mation and angiogenesis are increasingly being recognised as contributing to the pathogenesis, symptoms and progression of osteoarthritis. Beta-dystroglycan is a pivotal element of the transmembrane adhesion molecule involved in cell-extracellular matrix adhesion and angiogenesis. Matrix metalloproteinases are the main enzymes responsible for cartilage extracellular matrix breakdown and are also implicated in both angiogen-esis and beta-dystroglycan degradation in a number of malignancies. We aimed to investigate the expression and localisation of beta-dystroglycan and matrix metal-loproteinase 3, 9, and 13 within cartilage, synovium and synovial fluid and establish their roles in the pathogenesis of osteoarthritis.

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 beta-dystroglycan expression using Western Blotting and for the distribution of beta-dystroglycan, matrix metalloproteinase 3, 9, and 13 using immunohistochemistry on paraffin embedded tissue.

Results: Whilst no significant expression of beta-dystro-glycan was found in cartilage or synovial fluid, beta-dys-troglycan was expressed in the smooth muscle of both normal and osteoarthritic synovial blood vessels. Moreover, beta-dystroglycan was expressed in endothelium of blood vessels of osteoarthritic synovium, but not in the normal endothelium. In the endothelium of osteo-arthritic synovial blood vessels, beta-dystroglycan co-localised with matrix metalloproteinase 3 and 9. Discussion: Our results demonstrate that beta-dystro-glycan does not act as a cell adhesion molecule binding chondrocytes to the extracellular matrix. However, specific immunolocalisation of beta-dystroglycan within endothelium of inflamed osteoarthritic blood vessels suggests that beta-dystroglycan may play a role in angiogenesis associated with osteoarthritis. Its co-localisation with matrix metalloproteinase 3 and 9, previously reported to also have pro-angiogenic roles, may be linked. Further research is required to understand these roles more fully.