Changes in immunolocalisation of beta-dystroglycan and specific degradative enzymes in the osteoarthritic synovium.
OBJECTIVE
To investigate the immunolocalisation of beta-dystroglycan (beta-DG) and specific matrix metalloproteinases (MMPs)-3, -9, -13 and a disintegrin like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS-4) within the joint tissues of patients with osteoarthritis (OA) and unaffected controls.


METHODS
Cartilage, synovium and synovial fluid were obtained from the hip joints of five osteoarthritic (patients undergoing total hip replacement) and five control hip joints (patients undergoing hemiarthroplasty for femoral neck fracture). The samples were analysed for beta-DG protein using Western blot technique and by immunohistochemistry for tissue distribution of beta-DG, MMP-3, -9, -13, and ADAMTS-4.


RESULTS
beta-DG was detected in the smooth muscle of both normal and osteoarthritic synovial blood vessels. Importantly, beta-DG was detected in endothelium of blood vessels of OA synovium, but not in the control endothelium. In the endothelium of osteoarthritic synovial blood vessels, beta-DG co-localised with MMP-3 and -9. MMP-13 and ADAMTS-4 showed no endothelial staining, and only weak staining of the vascular smooth muscle was found. In contrast, we did not detect beta-DG protein in cartilage or synovial fluid.


CONCLUSIONS
beta-DG has been shown to have a role in angiogenesis, and our results demonstrate for the first time that there are clear differences in beta-DG staining between OA and control synovial blood vessels. The specific immunolocalisation of beta-DG within endothelium of inflamed OA blood vessels and its co-localisation with MMP-3 and -9, reported to have pro-angiogenic roles and believed to be involved in beta-DG cleavage, may also suggest that beta-DG plays a role in angiogenesis accompanying OA.
Wimsey
S
S
Department of Orthopaedic Surgery, Queen Alexandra Hospital, Portsmouth, UK. swimsey@hotmail.com <swimsey@hotmail.com>
Lien
C F
CF
Sharma
S
S
Brennan
P A
PA
Roach
H I
HI
Harper
G D
GD
Górecki
D C
DC
D051722:ADAM Proteins / Q000032:analysis*; D000071121:ADAMTS4 Protein; D015153:Blotting, Western / Q000379:methods; D002358:Cartilage, Articular / Q000201:enzymology / Q000378:metabolism; D049030:Dystroglycans / Q000032:analysis*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism; D006621:Hip Joint / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism; D015207:Osteoarthritis, Hip / Q000201:enzymology / Q000378:metabolism*; D011348:Procollagen N-Endopeptidase / Q000032:analysis*; D013582:Synovial Fluid / Q000201:enzymology / Q000378:metabolism; D013583:Synovial Membrane / Q000201:enzymology / Q000378:metabolism
C483081:DAG1 protein, human; D049030:Dystroglycans; D051722:ADAM Proteins; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D011348:Procollagen N-Endopeptidase; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human