PMID- 10513816
OWN - NLM
STAT- MEDLINE
DCOM- 19991027
LR  - 20190404
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 42
IP  - 9
DP  - 1999 Sep
TI  - Differential mechanisms of inorganic pyrophosphate production by plasma cell
      membrane glycoprotein-1 and B10 in chondrocytes.
PG  - 1986-97
AB  - OBJECTIVE: Increased nucleoside triphosphate pyrophosphohydrolase (NTPPPH)
      activity in chondrocytes is associated with cartilage matrix inorganic
      pyrophosphate (PPi) supersaturation in chondrocalcinosis. This study compared the
      roles of the transforming growth factor beta (TGFbeta)-inducible plasma cell
      membrane glycoprotein-1 (PC-1) and the closely related B10 NTPPPH activities in
      chondrocyte PPi metabolism. METHODS: NTPPPH expression was studied using reverse 
      transcriptase-polymerase chain reaction and Western blotting. Transmembrane PC-1 
      (tmPC-1), water-soluble secretory PC-1 (secPC-1), and transmembrane B10 were
      expressed by adenoviral gene transfer or plasmid transfection, and expression of 
      PPi was assessed in cultured articular chondrocytes and immortalized
      NTPPPH-deficient costal chondrocytes (TC28 cells). RESULTS: PC-1 and B10
      messenger RNA were demonstrated in articular cartilages in situ, in untreated
      cultured normal articular chondrocytes, and in TC28 cells. Expression of tmPC-1
      and secPC-1, but not B10, rendered the NTPPPH-deficient TC28 cells able to
      increase expression of extracellular PPi, with or without addition of TGFbeta (10
      ng/ml) to the media. More plasma membrane NTPPPH activity was detected in cells
      transfected with tmPC-1 than in cells transfected with B10. Furthermore, confocal
      microscopy with immunofluorescent staining of articular chondrocytes confirmed
      preferential plasma membrane localization of PC-1, relative to B10. Finally, both
      PC-1 and B10 increased the levels of intracellular PPi, but PC-1 and B10 appeared
      to act principally in different intracellular compartments (Golgi and post-Golgi 
      versus pre-Golgi, respectively). CONCLUSION: PC-1 and B10 NTPPPH activities were 
      not redundant in chondrocytes. Although increased PC-1 and B10 expression caused 
      elevations in intracellular PPi, the major effects of PC-1 and B10 were exerted
      in distinct subcellular compartments. Moreover, PC-1 (transmembrane and
      secreted), but not B10, increased the levels of extracellular PPi. Differential
      expression of PC-1 and B10 could modulate cartilage mineralization in
      degenerative joint diseases.
FAU - Johnson, K
AU  - Johnson K
AD  - Department of Veterans Affairs Medical Center, University of California, San
      Diego 92161, USA.
FAU - Vaingankar, S
AU  - Vaingankar S
FAU - Chen, Y
AU  - Chen Y
FAU - Moffa, A
AU  - Moffa A
FAU - Goldring, M B
AU  - Goldring MB
FAU - Sano, K
AU  - Sano K
FAU - Jin-Hua, P
AU  - Jin-Hua P
FAU - Sali, A
AU  - Sali A
FAU - Goding, J
AU  - Goding J
FAU - Terkeltaub, R
AU  - Terkeltaub R
LA  - eng
GR  - P01-AG-07996/AG/NIA NIH HHS/United States
GR  - P01-AR-43578/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Diphosphates)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 20350-15-6 (Brefeldin A)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.1.4.1 (Enpp3 protein, rat)
RN  - EC 3.1.4.1 (ectonucleotide pyrophosphatase phosphodiesterase 1)
RN  - EC 3.6.1.- (Pyrophosphatases)
RN  - EC 3.6.1.9 (nucleoside triphosphate pyrophosphatase)
SB  - AIM
SB  - IM
MH  - Brefeldin A/pharmacology
MH  - Cartilage, Articular/cytology
MH  - Cell Line
MH  - Chondrocytes/chemistry
MH  - Diphosphates/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Membrane Glycoproteins/biosynthesis/*pharmacology
MH  - *Phosphoric Diester Hydrolases
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Pyrophosphatases/metabolism/pharmacology
EDAT- 1999/10/08 00:00
MHDA- 1999/10/08 00:01
CRDT- 1999/10/08 00:00
PHST- 1999/10/08 00:00 [pubmed]
PHST- 1999/10/08 00:01 [medline]
PHST- 1999/10/08 00:00 [entrez]
AID - 10.1002/1529-0131(199909)42:9<1986::AID-ANR26>3.0.CO;2-O [doi]
PST - ppublish
SO  - Arthritis Rheum. 1999 Sep;42(9):1986-97. doi:
      10.1002/1529-0131(199909)42:9<1986::AID-ANR26>3.0.CO;2-O.