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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 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | 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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ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.92.22.10364 |