Bibliographic Details
| Title: |
Homogentisic acid induces morphological and mechanical aberration of ochronotic cartilage in alkaptonuria. |
| 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 |
| Source: |
Journal of Cellular Physiology; May2019, Vol. 234 Issue 5, p6696-6708, 13p |
| Subject Terms: |
ALKAPTONURIA, ARTICULAR cartilage, HOMEOSTASIS, CARTILAGE cells, PROTEOGLYCANS, GLYCOSAMINOGLYCANS, MAMMALS |
| 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. 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. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of Cellular Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
