Document Detail

Causal link between nucleotide pyrophosphohydrolase overactivity and increased intracellular inorganic pyrophosphate generation demonstrated by transfection of cultured fibroblasts and osteoblasts with plasma cell membrane glycoprotein-1. Relevance to calcium pyrophosphate dihydrate deposition disease.
MedLine Citation:
PMID:  8003067     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: In subjects with idiopathic calcium pyrophosphate dihydrate (CPPD) deposition disease, cartilage chondrocytes elaborate increased amounts of PPi. The mechanism of the intracellular PPi elevation is not known. Plasma membrane 5'-nucleotide phosphodiesterase I/nucleotide pyrophosphohydrolase (NTPPPH) activity also is elevated in chondrocytes and dermal fibroblasts of patients with idiopathic CPPD deposition disease. NTPPPH, as an ecto-enzyme, could act within certain intracellular compartments. Thus, we hypothesized a potential causal link between increased NTPPPH activity and increased intracellular PPi. METHODS: Transformed simian fibroblasts (COS cells) and human osteoblasts (U2OS cells) were transfected with the 5'-nucleotide phosphodiesterase I ecto-enzyme plasma cell membrane glycoprotein-1 (PC-1), recently shown to be expressed in cartilage, osteoblasts, and fibroblasts. RESULTS: Transfection with PC-1 markedly up-regulated 5'-nucleotode phosphodiesterase I activity and increased intracellular PPi concentrations by increasing the capacity of cells to generate PPi. Importantly, this did not require supplementation with exogenous nucleotides. CONCLUSION: Cellular overexpression of PC-1 produces NTPPPH overactivity and increased intracellular PPi generation in vitro. These findings support the potential importance of NTPPPH overactivity in PPi generation, both inside and outside the cell, in some subjects with CPPD deposition disease.
R Terkeltaub; M Rosenbach; F Fong; J Goding
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  37     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-07-08     Completed Date:  1994-07-08     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  934-41     Citation Subset:  AIM; IM    
Veterans Affairs Medical Center, University of California San Diego.
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MeSH Terms
Calcium Metabolism Disorders / enzymology,  metabolism
Cells, Cultured
Diphosphates / metabolism*
Fibroblasts / enzymology,  metabolism
Membrane Glycoproteins / biosynthesis,  pharmacology*
Osteoblasts / enzymology,  metabolism
Phosphodiesterase I
Phosphoric Diester Hydrolases / drug effects,  metabolism*
Pyrophosphatases / chemistry,  drug effects,  metabolism*
Grant Support
Reg. No./Substance:
0/Diphosphates; 0/Membrane Glycoproteins; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC I; EC pyrophosphatase phosphodiesterase 1; EC 3.6.1.-/Pyrophosphatases; EC triphosphate pyrophosphatase

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