Homogentisate 1,2 dioxygenase is expressed in human osteoarticular cells: Implications in alkaptonuria

Marcella Laschi,Annalisa Santucci,Enrico Selvi,Daniela Braconi,Lia Millucci,Loredana Amato,Laura Tinti,Giulia Bernardini,Adriano Spreafico,Lorenzo Ghezzi

doi:10.1002/jcp.24018

Marcella Laschi, Annalisa Santucci + Show 8 more

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https://doi.org/10.1002/jcp.24018

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Abstract

Alkaptonuria (AKU) results from defective homogentisate1,2-dioxygenase (HGD), causing degenerative arthropathy. The deposition of ochronotic pigment in joints is so far attributed to homogentisic acid produced by the liver, circulating in the blood and accumulating locally. Human normal and AKU osteoarticular cells were tested for HGD gene expression by RT-PCR, mono- and 2D-Western blotting. HGD gene expression was revealed in chondrocytes, synoviocytes, osteoblasts. Furthermore, HGD expression was confirmed by Western blotting, that also revealed the presence of five enzymatic molecular species. Our findings indicate that AKU osteoarticular cells produce the ochronotic pigment in loco and this may strongly contribute to induction of ochronotic arthropathy. J. Cell. Physiol. 227: 3254–3257, 2012. © 2011 Wiley Periodicals, Inc.

Highlights

MARCELLA LASCHI,1 LAURA TINTI,3 DANIELA BRACONI,1 LIA MILLUCCI,1 LORENZO GHEZZI,1 LOREDANA AMATO,1 ENRICO SELVI,2 ADRIANO SPREAFICO,2 GIULIA BERNARDINI,1 AND ANNALISA SANTUCCI1,2*
Our findings indicate that AKU osteoarticular cells produce the ochronotic pigment in loco and this may strongly contribute to induction of ochronotic arthropathy
We present results indicating that osteoarticular compartment cells express HGD and contribute to the production of local ochronosis in AKU arthropathy

Summary

Introduction

Alkaptonuria (AKU) results from defective homogentisate1,2-dioxygenase (HGD), causing degenerative arthropathy. The deposition of ochronotic pigment in joints is so far attributed to homogentisic acid produced by the liver, circulating in the blood and accumulating locally. Human normal and AKU osteoarticular cells were tested for HGD gene expression by RT-PCR, mono- and 2D-Western blotting. In AKU, HGA oxidizes to benzoquinone acetic acid that forms melanin-like polymers that are progressively deposited in the connective tissue, most commonly joints, cardiovascular system, kidney and skin causing a pathologic pigmentation known as ochronosis. The most severe AKU symptom is degenerative arthropathy resulting from ochronosis in joint tissues, especially in shoulders, hips and knees. Ochronotic pigment deposition in joints has been so far attributed to HGA excess produced by the liver, circulating in the blood and eventually accumulating in the osteoarticular tissue

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