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.

We made a prospective study of 111 children with acute hip pain to assess whether ultrasound can replace traditional radiography. An effusion was diagnosed in 71% by ultrasound but in only 15% by radiography. This effusion persisted for a mean of nine days; symptoms lasted for five days. Two patients found to have Perthes' disease had longer-lasting effusion and symptoms. Patients without an effusion had no obvious cause for their pain, so the pressure of an effusion from a transient synovitis does not account for all patients with irritable hips. Patients with an effusion persisting for over 24 days (the mean + 2 s.d. of our series) had more symptoms, a significantly larger effusion and greater limitation of movement. They may be more at risk for avascular necrosis. We found that radiographic examination influenced the immediate management of only two patients, those with Perthes' disease. We therefore propose a protocol of management for irritable hip, using ultrasonography at the first presentation of certain categories of patients. This would reduce the number of early radiographs by 75%.