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Anatomical Distribution of Ochronotic Pigment in Alkaptonuric Mice is Associated with Calcified Cartilage Chondrocytes at Osteochondral Interfaces

Hughes, JH, Keenan, CM, Sutherland, H, Edwards, HR, Wilson, PJM, Ranganath, LR, Jarvis, JC, Bou-Gharios, G and Gallagher, JA (2020) Anatomical Distribution of Ochronotic Pigment in Alkaptonuric Mice is Associated with Calcified Cartilage Chondrocytes at Osteochondral Interfaces. Calcified Tissue International. ISSN 0171-967X

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Abstract

Alkaptonuria (AKU) is characterised by increased circulating homogentisic acid and deposition of ochronotic pigment in collagen-rich connective tissues (ochronosis), stiffening the tissue. This process over many years leads to a painful and severe osteoarthropathy, particularly affecting the cartilage of the spine and large weight bearing joints. Evidence in human AKU tissue suggests that pigment binds to collagen. The exposed collagen hypothesis suggests that collagen is initially protected from ochronosis, and that ageing and mechanical loading causes loss of protective molecules, allowing pigment binding. Schmorl’s staining has previously demonstrated knee joint ochronosis in AKU mice. This study documents more comprehensively the anatomical distribution of ochronosis in two AKU mouse models (BALB/c Hgd−/−, Hgd tm1a−/−), using Schmorl’s staining. Progression of knee joint pigmentation with age in the two AKU mouse models was comparable. Within the knee, hip, shoulder, elbow and wrist joints, pigmentation was associated with chondrons of calcified cartilage. Pigmented chondrons were identified in calcified endplates of intervertebral discs and the calcified knee joint meniscus, suggesting that calcified tissues are more susceptible to pigmentation. There were significantly more pigmented chondrons in lumbar versus tail intervertebral disc endplates (p = 0.002) and clusters of pigmented chondrons were observed at the insertions of ligaments and tendons. These observations suggest that loading/strain may be associated with increased pigmentation but needs further experimental investigation. The calcified cartilage may be the first joint tissue to acquire matrix damage, most likely to collagen, through normal ageing and physiological loading, as it is the first to become susceptible to pigmentation.

Item Type: Article
Uncontrolled Keywords: 0601 Biochemistry and Cell Biology, 0903 Biomedical Engineering, 1103 Clinical Sciences
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Biological & Environmental Sciences (new Sep 19)
Sport & Exercise Sciences
Publisher: Springer
Related URLs:
Date Deposited: 04 Dec 2020 12:41
Last Modified: 04 Dec 2020 12:45
DOI or Identification number: 10.1007/s00223-020-00764-6
URI: https://researchonline.ljmu.ac.uk/id/eprint/14133

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