Linked Life Data

10620061

Source:http://linkedlifedata.com/resource/pubmed/id/10620061

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-1-27
pubmed:abstractText
The mechanism by which inactivating mutations of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) cause X-linked hypophosphatemia remains unknown. However, recent reports suggest errant PHEX activity in osteoblasts may fail to inactivate a phosphaturic factor produced by these cells. To test this possibility, we examined coordinated maturational expression of PHEX and production of phosphate transport inhibitory activity in osteoblasts from normal and hyp-mice. We assessed the inhibitory activity in conditioned medium by examining the effects on opossum kidney cell phosphate transport and osteoblast PHEX expression by reverse transcriptase-polymerase chain reaction during a 17-day maturational period. Inhibitory activity increased as a function of osteoblast maturational stage, with no activity after 3 days and persistent activity by 6 days of culture. More significantly, equal phosphate transport inhibitory activity in conditioned medium from normal and hyp-mouse osteoblasts (control 1.90 +/- 0.12, normal 1.48 +/- 0.10, hyp 1.45 +/- 0.04 nmol/mg of protein/minute) was observed at 6 days. However, by 10 days hyp-mouse osteoblasts exhibited greater inhibitory activity than controls, and by 17 days the difference in phosphate transport inhibition maximized (control 2.08 +/- 0.09, normal 1.88 +/- 0.06, hyp 1.58 +/- 0.06 nmol/mg of protein/minute). Concurrently, we observed absent PHEX expression in normal osteoblasts after 3 days, limited production at 6 days, and significant production by day 10 of culture, while hyp-mouse osteoblasts exhibited limited PHEX activity secondary to an inactivating mutation. The data suggest that the presence of inactivating PHEX mutations results in the enhanced renal phosphate transport inhibitory activity exhibited by hyp-mouse osteoblasts.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0884-0431
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2027-35
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10620061-Animals, pubmed-meshheading:10620061-Biological Transport, pubmed-meshheading:10620061-Carrier Proteins, pubmed-meshheading:10620061-Cell Line, pubmed-meshheading:10620061-Culture Media, Conditioned, pubmed-meshheading:10620061-Disease Models, Animal, pubmed-meshheading:10620061-Gene Expression Regulation, pubmed-meshheading:10620061-Hypophosphatemia, pubmed-meshheading:10620061-Kidney, pubmed-meshheading:10620061-Mice, pubmed-meshheading:10620061-Mice, Transgenic, pubmed-meshheading:10620061-Mutation, pubmed-meshheading:10620061-Opossums, pubmed-meshheading:10620061-Osteoblasts, pubmed-meshheading:10620061-PHEX Phosphate Regulating Neutral Endopeptidase, pubmed-meshheading:10620061-Phenotype, pubmed-meshheading:10620061-Phosphates, pubmed-meshheading:10620061-Protein Biosynthesis, pubmed-meshheading:10620061-Proteins, pubmed-meshheading:10620061-RNA, Messenger, pubmed-meshheading:10620061-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10620061-Sodium-Phosphate Cotransporter Proteins, pubmed-meshheading:10620061-Symporters
pubmed:year
1999
pubmed:articleTitle
Coordinated maturational regulation of PHEX and renal phosphate transport inhibitory activity: evidence for the pathophysiological role of PHEX in X-linked hypophosphatemia.
pubmed:affiliation
Departments of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.