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Erschienen in: Calcified Tissue International 2/2011

01.08.2011 | Original Research

An Atypical Degenerative Osteoarthropathy in Hyp Mice is Characterized by a Loss in the Mineralized Zone of Articular Cartilage

verfasst von: Guoying Liang, Joshua VanHouten, Carolyn M. Macica

Erschienen in: Calcified Tissue International | Ausgabe 2/2011

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Abstract

Patients with X-linked hypophosphatemia (XLH) develop enthesophytes and osteophytes secondary to articular cartilage degeneration and together are the primary cause of morbidity in adult patients so afflicted. We have previously characterized the enthesopathy in Hyp mice, a murine model of XLH. We now extend these studies to the synovial joint in order to characterize potential cellular changes in articular cartilage that may predispose patients to the osteoarthropathy of XLH. We report that, despite highly elevated levels of alkaline phosphatase activity throughout articular cartilage, there is a complete loss in the mineralized zone of articular cartilage as assessed by von Kossa staining of mineral and as quantified by EPIC-microCT analysis and evidence of vascular invasion. We also identify the downregulation of extracellular matrix (ECM) factors identified as regulators of terminally differentiated mineralizing articular chondrocytes. There is also a striking increase in the histochemical staining of sulfated proteoglycans, a change that may reflect the loss of a transitional tissue that reduces mechanical stress at the interface between cartilage and subchondral bone. The failure of mineralizing articular chondrocytes to develop in the hypophosphatemic state suggests that phosphate may be a key regulator of chondrocyte mineralization. Accordingly, we find that the appropriate zonal arrangement and phenotypic markers of articular cartilage are significantly reestablished by phosphate-replacement therapy. Given the turnover and maintenance of articular cartilage ECM, the identification of early and abnormal cellular changes unique to XLH will undoubtedly aid in a more effective management of this disease to minimize the onset of degenerative osteoarthropathy.
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Metadaten
Titel
An Atypical Degenerative Osteoarthropathy in Hyp Mice is Characterized by a Loss in the Mineralized Zone of Articular Cartilage
verfasst von
Guoying Liang
Joshua VanHouten
Carolyn M. Macica
Publikationsdatum
01.08.2011
Verlag
Springer-Verlag
Erschienen in
Calcified Tissue International / Ausgabe 2/2011
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-011-9502-4

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