Homogentisic acid induces cytoskeleton and extracellular matrix alteration in alkaptonuric cartilage.

Journal of cellular physiology 2021 Aug

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Alkaptonuria (AKU) is an ultra-rare disease caused by the deficient activity of homogentisate 1,2-dioxygenase enzyme, leading the accumulation of homogentisic acid (HGA) in connective tissues implicating the formation of a black pigmentation called "ochronosis." Although AKU is a multisystemic disease, the most affected tissue is the articular cartilage, which during the pathology appears to be highly damaged. In this study, a model of alkaptonuric chondrocytes and cartilage was realized to investigate the role of HGA in the alteration of the extracellular matrix (ECM). The AKU tissues lost its architecture composed of collagen, proteoglycans, and all the proteins that characterize the ECM. The cause of this alteration in AKU cartilage is attributed to a degeneration of the cytoskeletal network in chondrocytes caused by the accumulation of HGA. The three cytoskeletal proteins, actin, vimentin, and tubulin, were analyzed and a modification in their amount and disposition in AKU chondrocytes model was identified. Cytoskeleton is involved in many fundamental cellular processes; therefore, the aberration in this complex network is involved in the manifestation of AKU disease. © 2021 Wiley Periodicals LLC.

Citation

Silvia Galderisi, Vittoria Cicaloni, Maria S Milella, Lia Millucci, Michela Geminiani, Laura Salvini, Laura Tinti, Cristina Tinti, Otilia V Vieira, Liliana S Alves, Alvaro H Crevenna, Ottavia Spiga, Annalisa Santucci. Homogentisic acid induces cytoskeleton and extracellular matrix alteration in alkaptonuric cartilage. Journal of cellular physiology. 2021 Aug;236(8):6011-6024