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    Rights statement: This is the author’s version of a work that was accepted for publication in Osteoarthritis and Cartilage. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Osteoarthritis and Cartilage, 27 (8), 2019 DOI: 10.1016/j.joca.2019.04.012

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Raman Spectroscopy identifies differences in ochronotic and non-ochronotic cartilage: a potential novel technique for monitoring ochronosis

Research output: Contribution to journalJournal article

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<mark>Journal publication date</mark>1/08/2019
<mark>Journal</mark>Osteoarthritis and Cartilage
Issue number8
Volume27
Number of pages8
Pages (from-to)1244-1251
Publication statusPublished
Early online date22/04/19
Original languageEnglish

Abstract

Objective
Alkaptonuria (AKU) is a rare, inherited disorder of tyrosine metabolism, where patients are unable to breakdown homogentisic acid (HGA), which increases systemically over time. It presents with a clinical triad of features; HGA in urine, ochronosis of collagenous tissues, and the subsequent ochronotic arthritis of these tissues. In recent years the advance in the understanding of the disease and the potential treatment of the disorder looks promising with the data on the efficacy of nitisinone. However, there are limited methods for the detection and monitoring of ochronosis in vivo, or for treatment monitoring.
The study aim was to test the hypothesis that Raman spectra would identify a distinct chemical fingerprint for the non-ochronotic, compared to ochronotic cartilage.

Design:
Ochronotic and non-ochronotic cartilage from human hips and ears were analysed using Raman spectroscopy.

Results:
Non-ochronotic cartilage spectra were similar and reproducible and typical of normal articular cartilage. Conversely, the ochronotic cartilage samples were highly fluorescent and displayed limited or no discernible Raman peaks in the spectra, in stark contrast to their non-ochronotic pairs. Interestingly, a novel peak was observed associated with the polymer of HGA in the ochronotic cartilage that was confirmed by analysis of pigment derived from synthetic HGA.

Conclusion:
This technique reveals novel data on the chemical differences in ochronotic compared with non-ochronotic cartilage, these differences are detectable by a technique that is already generating in vivo data and demonstrates the first possible procedure to monitor the progression of ochronosis in tissues of patients with AKU.

Bibliographic note

This is the author’s version of a work that was accepted for publication in Osteoarthritis and Cartilage. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Osteoarthritis and Cartilage, 27 (8), 2019 DOI: 10.1016/j.joca.2019.04.012