Homogentisic acid induces morphological and mechanical aberration of ochronotic cartilage in alkaptonuria. Issue 5 (20th October 2018)

• Record Type: Journal Article
• Authors: Bernardini, Giulia; Leone, Gemma; Millucci, Lia; Consumi, Marco; Braconi, Daniela; Spiga, Ottavia; Galderisi, Silvia; Marzocchi, Barbara; Viti, Cecilia; Giorgetti, Giovanna; Lupetti, Pietro; Magnani, Agnese; Santucci, Annalisa
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 5(2019:May)
• Page Start: 6696
• Page End: 6708
• Publication Date: 2018-10-20
• Subjects: alkaptonuria -- glycosaminoglycan -- heat capacity -- mesoporosity -- ochronosis -- rheology; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.27416
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Alkaptonuria (AKU) is a disease caused by a deficient homogentisate 1, 2‐dioxygenase activity leading to systemic accumulation of homogentisic acid (HGA), that forms a melanin‐like polymer that progressively deposits onto connective tissues causing a pigmentation called "ochronosis" and tissue degeneration. The effects of AKU and ochronotic pigment on the biomechanical properties of articular cartilage need further investigation. To this aim, AKU cartilage was studied using thermal (thermogravimetry and differential scanning calorimetry) and rheological analysis. We found that AKU cartilage had a doubled mesopore radius compared to healthy cartilage. Since the mesoporous structure is the main responsible for maintaining a correct hydrostatic pressure and tissue homoeostasis, drastic changes of thermal and rheological parameters were found in AKU. In particular, AKU tissue lost its capability to enhance chondrocytes metabolism (decreased heat capacity) and hence the production of proteoglycans. A drastic increase in stiffness and decrease in dissipative and lubricant role ensued in AKU cartilage. Multiphoton and scanning electron microscopies revealed destruction of cell–matrix microstructure and disruption of the superficial layer. Such observations on AKU specimens were confirmed in HGA‐treated healthy cartilage, indicating that HGA is the toxic responsible of morphological and mechanical alterations of cartilage in AKU. Abstract : Although efforts were made, the exact biochemical mechanism of cartilage degradation in alkaptonuria (AKU) is not clarified in detail yet. Our multidisciplinary study provides novel insights on how homogentisic acid and the ochronotic pigment affect the physico–thermal and mechanical properties of AKU cartilage.