Angiogenesis in alkaptonuria.
Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of AKU treatment is palliative and little is known about its physiopathology. Neovascularization is involved in the pathogenesis of systemic inflammatory rheumatic diseases, a family of related disorders that includes AKU. Here, we investigated the presence of neoangiogenesis in AKU synovium and healthy controls. Synovium from AKU patients, who had undergone total joint replacement or arthroscopy, or from healthy patients without any history of rheumatic diseases, who underwent surgical operation following sport trauma was subjected to hematoxylin and eosin staining. Histologic grades were assigned for clinical disease activity and synovitis based on cellular content of the synovium. By immunofluorescence microscopy, using different endothelial cell markers, we observed large vascularization in AKU but not in healthy synovium. Moreover, Western blotting and quantification analyses confirmed strong expression of endothelial cell markers in AKU synovial tissues. Importantly, AKU synovium vascular endothelium expressed high levels of β-dystroglycan, a protein previously involved in the regulation of angiogenesis in osteoarthritic synovium. This is the first report providing experimental evidences that new blood vessels are formed in AKU synovial tissues, opening new perspectives for AKU therapy.
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy.
Lia
L
Millucci
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy.
Giulia
G
Bernardini
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy.
Barbara
B
Marzocchi
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy.
Daniela
D
Braconi
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy.
Michela
M
Geminiani
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy.
Silvia
S
Gambassi
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy.
Marcella
M
Laschi
Department of Medicine, Surgery and Neurosciences, Rheumatology section, University of Siena, Policlinico Le Scotte, 53100, Siena, Italy.
Bruno
B
Frediani
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy.
Federico
F
Galvagni
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy.
Maurizio
M
Orlandini
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy. annalisa.santucci@unisi.it.
Annalisa
0000-0001-6976-9086
A
Santucci
D000474:Alkaptonuria / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D049030:Dystroglycans / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D013583:Synovial Membrane / Q000473:pathology
D015415:Biomarkers; D049030:Dystroglycans
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