Source:http://linkedlifedata.com/resource/pubmed/id/19609735
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2009-8-27
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| pubmed:abstractText |
X-linked hypophosphatemia (XLH) is characterized by rickets and osteomalacia as a result of an inactivating mutation of the PHEX (phosphate-regulating gene with homology to endopeptidases on the X chromosome) gene. PHEX encodes an endopeptidase that, when inactivated, results in elevated circulating levels of FGF-23, a novel phosphate-regulating hormone (a phosphatonin), thereby resulting in increased phosphate excretion and impaired bone mineralization. A generalized and severe mineralizing enthesopathy in patients with XLH was first reported in 1985; we likewise report a survey in which we found evidence of enthesopathy in fibrocartilaginous insertion sites, as well as osteophyte formation, in the majority of patients. Nonetheless, there has been very little focus on the progression and pathogenesis underlying the paradoxical heterotopic calcification of tendon and ligament insertion sites. Such studies have been hampered by lack of a model of mineralizing enthesopathy. We therefore characterized the involvement of the most frequently targeted fibrocartilaginous tendon insertion sites in Hyp mice, a murine model of the XLH mutation that phenocopies the human syndrome in every detail including hypophosphatemia and elevated FGF-23. Histological examination of the affected entheses revealed that mineralizing insertion sites, while thought to involve bone spur formation, were not due to bone-forming osteoblasts but instead to a significant expansion of mineralizing fibrocartilage. Our finding that enthesis fibrocartilage cells specifically express fibroblast growth factor receptor 3 (FGFR3)/Klotho suggests that the high circulating levels of FGF-23, characteristic of XLH and Hyp mice, may be part of the biochemical milieu that underlies the expansion of mineralizing enthesis fibrocartilage.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1432-0827
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
85
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
235-46
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| pubmed:dateRevised |
2011-9-26
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| pubmed:meshHeading |
pubmed-meshheading:19609735-Achilles Tendon,
pubmed-meshheading:19609735-Adolescent,
pubmed-meshheading:19609735-Adult,
pubmed-meshheading:19609735-Aged,
pubmed-meshheading:19609735-Animals,
pubmed-meshheading:19609735-Biological Markers,
pubmed-meshheading:19609735-Calcinosis,
pubmed-meshheading:19609735-Child,
pubmed-meshheading:19609735-Disease Models, Animal,
pubmed-meshheading:19609735-Disease Progression,
pubmed-meshheading:19609735-Female,
pubmed-meshheading:19609735-Fibroblast Growth Factors,
pubmed-meshheading:19609735-Humans,
pubmed-meshheading:19609735-Hypophosphatemic Rickets, X-Linked Dominant,
pubmed-meshheading:19609735-Mice,
pubmed-meshheading:19609735-Mice, Inbred C57BL,
pubmed-meshheading:19609735-Middle Aged,
pubmed-meshheading:19609735-Patellar Ligament,
pubmed-meshheading:19609735-Phenotype,
pubmed-meshheading:19609735-Quadriceps Muscle,
pubmed-meshheading:19609735-Rheumatic Diseases,
pubmed-meshheading:19609735-Tendinopathy,
pubmed-meshheading:19609735-Tendons,
pubmed-meshheading:19609735-Young Adult
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| pubmed:year |
2009
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| pubmed:articleTitle |
Survey of the enthesopathy of X-linked hypophosphatemia and its characterization in Hyp mice.
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| pubmed:affiliation |
Department of Internal Medicine/Endocrinology, Yale University, P.O. Box 208020, New Haven, CT 06520-8020, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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