Faculty Collaboration Database

Purine receptors modulate chondrocyte extracellular inorganic pyrophosphate production. Osteoarthritis Cartilage 2010 Nov;18(11):1496-501

Date

08/17/2010

Pubmed ID

20709180

Pubmed Central ID

PMC2975862

DOI

10.1016/j.joca.2010.08.004

Scopus ID

2-s2.0-78149415406 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

OBJECTIVE: Extracellular inorganic pyrophosphate (ePPi) plays a key role in the regulation of normal and pathologic mineralization. The purpose of this work was to evaluate the role of P1 and P2 purine receptors in modulating ePPi production by articular chondrocytes.

METHODS: Porcine cartilage explants and chondrocyte monolayers were cultured in the presence of P1 agonists, or a P2 agonist or antagonist and inhibitors of P2 signaling. Ambient media ePPi concentrations were measured after 48-96h.

RESULTS: The P1 agonists NECA and CGS 21680 significantly decreased ePPi concentrations surrounding chondrocytes and cartilage explants. The P2 agonist, ADP, increased ePPi levels, and the P2 antagonist, suramin, decreased ePPi concentrations. Thapsigargin and 1,2 bis-(2-aminophenoxy)ethane-N,N,N'N'-tetra acetic acid (BAPTA), which dampen Ca(2+)-related P2 signaling, suppressed the response to ADP.

CONCLUSIONS: Purine receptors are important regulators of ePPi production by chondrocytes. P1 receptor stimulation diminishes and P2 receptor stimulation enhances ePPi production. Alterations in receptor signaling or aberrations of extracellular purine nucleotide metabolism resulting in abnormal quantities or proportions of P1 and P2 receptor ligands could foster changes in ePPi production that in turn affect mineralization. We propose a homeostatic role for extracellular purine nucleotides and purine receptors in stabilizing ePPi concentrations.

Author List

Rosenthal AK, Hempel D, Kurup IV, Masuda I, Ryan LM

Author

Ann K. Rosenthal MD Associate Dean, Chief, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Diphosphate
Animals
Cartilage, Articular
Cells, Cultured
Chondrocytes
Cyclic AMP
Diphosphates
Purinergic P1 Receptor Agonists
Purinergic P2 Receptor Agonists
Purinergic P2 Receptor Antagonists
RNA, Messenger
Receptors, Purinergic
Suramin
Swine