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Title: Chondroptosis in alkaptonuric cartilage
Authors: Millucci, Lia 
Giorgetti, Giovanna
Viti, Cecilia
Ghezzi, Lorenzo
Gambassi, Silvia
Braconi, Daniela 
Marzocchi, Barbara 
Paffetti, Alessandro 
Lupetti, Pietro
Bernardini, Giulia 
Orlandini, Maurizio 
Santucci, Annalisa 
Keywords: Adult; Aged; Aged, 80 and over; Aldehydes; Alkaptonuria; Cartilage; Chondrocytes; Enzyme Activation; Female; GTP-Binding Proteins; Humans; Joints; Male; Middle Aged; Osteoarthritis; Spectrometry, X-Ray Emission; Staining and Labeling; Transglutaminases; Apoptosis
Issue Date: 2015
Project: None 
Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of treatment is palliative and little is known about AKU physiopathology. Chondroptosis, a peculiar type of cell death in cartilage, has been so far reported to occur in osteoarthritis, a rheumatic disease that shares some features with AKU. In the present work, we wanted to assess if chondroptosis might also occur in AKU. Electron microscopy was used to detect the morphological changes of chondrocytes in damaged cartilage distinguishing apoptosis from its variant termed chondroptosis. We adopted histological observation together with Scanning Electron Microscopy and Transmission Electron Microscopy to evaluate morphological cell changes in AKU chondrocytes. Lipid peroxidation in AKU cartilage was detected by fluorescence microscopy. Using the above-mentioned techniques, we performed a morphological analysis and assessed that AKU chondrocytes undergo phenotypic changes and lipid oxidation, resulting in a progressive loss of articular cartilage structure and function, showing typical features of chondroptosis. To the best of our knowledge, AKU is the second chronic pathology, following osteoarthritis, where chondroptosis has been documented. Our results indicate that Golgi complex plays an important role in the apoptotic process of AKU chondrocytes and suggest a contribution of chondroptosis in AKU pathogenesis. These findings also confirm a similarity between osteoarthritis and AKU.
ISSN: 0021-9541
DOI: 10.1002/jcp.24850
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