title: Chondroptosis in alkaptonuric cartilage.
abstract: 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.
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
authors.forename: Lia
authors.initials: L
authors.lastname: Millucci
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giorgetti
authors.forename: Cecilia
authors.initials: C
authors.lastname: Viti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghezzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Gambassi
authors.forename: Daniela
authors.initials: D
authors.lastname: Braconi
authors.forename: Barbara
authors.initials: B
authors.lastname: Marzocchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Paffetti
authors.forename: Pietro
authors.initials: P
authors.lastname: Lupetti
authors.forename: Giulia
authors.initials: G
authors.lastname: Bernardini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Orlandini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Santucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism; D000474:Alkaptonuria / Q000473:pathology*; D017209:Apoptosis; D002356:Cartilage / Q000473:pathology* / Q000648:ultrastructure; D019902:Chondrocytes / Q000473:pathology* / Q000648:ultrastructure; D004789:Enzyme Activation; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007596:Joints / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013052:Spectrometry, X-Ray Emission; D013194:Staining and Labeling; D011503:Transglutaminases / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; C027576:4-hydroxy-2-nonenal