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Homogentisic acid affects human osteoblastic functionality by oxidative stress and alteration of the Wnt/β‐catenin signaling pathway
Author(s) -
Schiavone Maria Lucia,
Millucci Lia,
Bernardini Giulia,
Giustarini Daniela,
Rossi Ranieri,
Marzocchi Barbara,
Santucci Annalisa
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29575
Subject(s) - homogentisic acid , oxidative stress , alkaptonuria , ochronosis , wnt signaling pathway , chemistry , oxidative phosphorylation , spinal osteoarthropathy , cancer research , inflammation , medicine , biochemistry , signal transduction , pathology
Alkaptonuria (AKU) is a rare disease correlated with deficiency of the enzyme homogentisate 1,2 dioxygenase, which causes homogentisic acid (HGA) accumulation. HGA is subjected to oxidation/polymerization reactions, leading to the production of a peculiar melanin‐like pigmentation (ochronosis) after chronic inflammation, which is considered as a triggering event for the generation of oxidative stress. Clinical manifestations of AKU are urine darkening, sclera pigmentation, early severe osteoarthropathy, and cardiovascular and renal complication. Despite major clinical manifestations of AKU being observed in the bones and skeleton, the molecular and functional parameters are so far unknown in AKU. In the present study, we used human osteoblasts supplemented with HGA as a AKU cellular model. We observed marked oxidative stress, and for the first time, we were able to correlate HGA deposition with an impairment in the Wnt/β‐catenin signaling pathway, opening a range of possible therapeutic strategies for a disease still lacking a known cure.