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  • Rheumatology AKU cartilage ageing biomarkers PURE

    Rights statement: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Rheumatology following peer review. The definitive publisher-authenticated version Adam M. Taylor, Ming-Feng Hsueh, Lakshminarayan R. Ranganath, James A. Gallagher, Jane P. Dillon, Janet L. Huebner, Jon B. Catterall, and Virginia B. Kraus Cartilage biomarkers in the osteoarthropathy of alkaptonuria reveal low turnover and accelerated ageing Rheumatology 2017 56 (1) 156-164 doi:10.1093/rheumatology/kew355

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Cartilage biomarkers in the osteoarthropathy of alkaptonuria reveal low turnover and accelerated ageing

Research output: Contribution to Journal/MagazineJournal articlepeer-review

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  • Adam Michael Taylor
  • Ming-Feng Hsueh
  • Lakshminarayan Ranganath
  • James Gallagher
  • Jane Dillon
  • Janet Huebner
  • Jon Catterall
  • Virginia Byers Kraus
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<mark>Journal publication date</mark>01/2017
<mark>Journal</mark>Rheumatology
Issue number1
Volume56
Number of pages9
Pages (from-to)156-164
Publication StatusPublished
Early online date7/10/16
<mark>Original language</mark>English

Abstract

Objective. Alkaptonuria (AKU) is a rare autosomal recessive disease resulting from a single enzyme deficiency in tyrosine metabolism. As a result, homogentisic acid cannot be metabolized, causing systemic increases. Over time, homogentisic acid polymerizes and deposits in collagenous tissues, leading to ochronosis. Typically, this occurs in joint cartilages, leading to an early onset, rapidly progressing osteoarthropathy. The aim of this study was to examine tissue turnover in cartilage affected by ochronosis and its role in disease initiation and progression.

Methods. With informed patient consent, hip and knee cartilages were obtained at surgery for arthropathy due to AKU (n = 6; 2 knees/4 hips) and OA (n = 12; 5 knees/7 hips); healthy non-arthritic (non-OA n = 6; 1 knee/5 hips) cartilages were obtained as waste from trauma surgery. We measured cartilage concentrations (normalized to dry weight) of racemized aspartate, GAG, COMP and deamidated COMP (D-COMP). Unpaired AKU, OA and non-OA samples were compared by non-parametric Mann–Whitney U test.

Results. Despite more extractable total protein being obtained from AKU cartilage than from OA or non-OA cartilage, there was significantly less extractable GAG, COMP and D-COMP in AKU samples compared with OA and non-OA comparators. Racemized Asx (aspartate and asparagine) was significantly enriched in AKU cartilage compared with in OA cartilage.

Conclusions. These novel data represent the first examination of cartilage matrix components in a sample of patients with AKU, representing almost 10% of the known UK alkaptonuric population. Compared with OA and non-OA, AKU cartilage demonstrates a very low turnover state and has low levels of extractable matrix proteins.

Bibliographic note

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Rheumatology following peer review. The definitive publisher-authenticated version Adam M. Taylor, Ming-Feng Hsueh, Lakshminarayan R. Ranganath, James A. Gallagher, Jane P. Dillon, Janet L. Huebner, Jon B. Catterall, and Virginia B. Kraus Cartilage biomarkers in the osteoarthropathy of alkaptonuria reveal low turnover and accelerated ageing Rheumatology 2017 56 (1) 156-164 doi: 10.1093/rheumatology/kew355 doi:10.1093/rheumatology/kew355