Cartilage biomarkers in the osteoarthropathy of alkaptonuria reveal low turnover and accelerated ageing
| Autor: | Lakshminarayan R. Ranganath, Janet L. Huebner, James A. Gallagher, Virginia B. Kraus, M.-F. Hsueh, J.P. Dillon, Adam Michael Taylor, Jon B. Catterall |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Cartilage
Articular Male 0301 basic medicine Aging Pathology Knee Joint Osteoarthritis Cartilage Oligomeric Matrix Protein Alkaptonuria Osteoarthritis Hip chemistry.chemical_compound 0302 clinical medicine Spinal osteoarthropathy Pharmacology (medical) Glycosaminoglycans Aged 80 and over education.field_of_study biology Middle Aged Osteoarthritis Knee medicine.anatomical_structure Female Hip Joint Joint Diseases Adult musculoskeletal diseases medicine.medical_specialty Population Young Adult 03 medical and health sciences Rheumatology medicine Humans Homogentisic acid education Aged 030203 arthritis & rheumatology Cartilage oligomeric matrix protein Aspartic Acid Ochronosis Basic and Translational Science business.industry Cartilage medicine.disease 030104 developmental biology chemistry Case-Control Studies biology.protein business Biomarkers |
| Zdroj: | RHEUMATOLOGY |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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