Abstract
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.
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Abbreviations
- AKU:
-
Alkaptonuria
- EC:
-
Endothelial cell
- vWill:
-
Von Willebrand factor
- VE-cad:
-
VE-cadherin
- β-DG:
-
β-dystroglycan
- MVD:
-
Microvessel density
- MVA:
-
Microvessel area
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Acknowledgments
We thank Dr. Dario Gambera and Prof. Pier Paolo Mariani for assisting in sample collection and AIMAKU (Associazione Italiana Malati di Alkaptnoria) for its support. This work was funded by Telethon Italy (grant GGP10058).
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All procedures followed were in accordance with the ethical standards of the responsible committee on human exper- imentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all parents of patients for being included in the study.
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Communicated by: Bruce A. Barshop
Lia Millucci and Maurizio Orlandini contributed equally to this work.
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Millucci, L., Bernardini, G., Marzocchi, B. et al. Angiogenesis in alkaptonuria. J Inherit Metab Dis 39, 801–806 (2016). https://doi.org/10.1007/s10545-016-9976-3
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DOI: https://doi.org/10.1007/s10545-016-9976-3