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Interleukin 1β Suppresses Transforming Growth Factor-Induced Inorganic Pyrophosphate (PPi) Production and Expression of the PPi- Generating Enzyme PC-1 in Human Chondrocytes

Articular cartilage chondrocytes have the unique ability to elaborate large amounts of extracellular pyrophosphate (PPi), and transforming growth factor β (TGFβ) appears singular among cartilage regulatory factors in stimulating PPiproduction. TGFβ caused a time and dose-dependent increase in intrac...

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Published in:Proceedings of the National Academy of Sciences - PNAS 1995-10, Vol.92 (22), p.10364-10368
Main Authors: Lotz, Martin, Rosen, Fred, McCabe, Greg, Quach, Jacqueline, Blanco, Francisco, Dudler, Jean, Solan, Joell, Goding, James, Seegmiller, J. Edwin, Terkeltaub, Robert
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container_issue 22
container_start_page 10364
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 92
creator Lotz, Martin
Rosen, Fred
McCabe, Greg
Quach, Jacqueline
Blanco, Francisco
Dudler, Jean
Solan, Joell
Goding, James
Seegmiller, J. Edwin
Terkeltaub, Robert
description Articular cartilage chondrocytes have the unique ability to elaborate large amounts of extracellular pyrophosphate (PPi), and transforming growth factor β (TGFβ) appears singular among cartilage regulatory factors in stimulating PPiproduction. TGFβ caused a time and dose-dependent increase in intracellular and extracellular PPiin human articular chondrocyte cultures. TGFβ and interleukin 1β (IL-1β) antagonistically regulate certain chondrocyte functions. IL-1β profoundly inhibited basal and TGFβ-induced PPielaboration. To address mechanisms involved with the regulation of PPisynthesis by IL-1β and TGFβ, we analyzed the activity of the PPi-generating enzyme NTP pyrophosphohydrolase (NTPPPH) and the PPi-hydrolyzing enzyme alkaline phosphatase. Human chondrocyte NTPPPH activity was largely attributable to plasma cell membrane glycoprotein 1, PC-1. Furthermore, TGFβ induced comparable increases in the activity of extracellular PPi, intracellular PPi, and cellular NTPPPH and in the levels of PC-1 protein and mRNA in chondrocytes as well as a decrease in alkaline phosphatase. All of these TGFβ-induced responses were completely blocked by IL-1β. Thus, IL-1β may be an important regulator of mineralization in chondrocytes by inhibiting TGFβ-induced PPiproduction and PC-1 expression.
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ispartof Proceedings of the National Academy of Sciences - PNAS, 1995-10, Vol.92 (22), p.10364-10368
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subjects Adult
Aged
Alkaline Phosphatase - metabolism
Arthritis
Ascites
Blotting, Western
Cartilage
Cartilage, Articular - drug effects
Cartilage, Articular - metabolism
Cell culture techniques
Cells, Cultured
Chondrocytes
Culture Media, Conditioned
Diphosphates
Diphosphates - metabolism
DNA
DNA - metabolism
Gene Expression - drug effects
Homeostasis
Humans
Interleukin-1 - pharmacology
Kinetics
Membrane Glycoproteins - biosynthesis
Messenger RNA
Middle Aged
Phosphatases
Phosphoric Diester Hydrolases
Plasma cells
Pyrophosphatases - metabolism
RNA, Messenger - analysis
RNA, Messenger - biosynthesis
Transforming Growth Factor beta - antagonists & inhibitors
Transforming Growth Factor beta - pharmacology
title Interleukin 1β Suppresses Transforming Growth Factor-Induced Inorganic Pyrophosphate (PPi) Production and Expression of the PPi- Generating Enzyme PC-1 in Human Chondrocytes
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