BACKGROUND AND PURPOSE: The expression and function of P2X(7) receptors in osteoclasts is well established, but less is known about their role in osteoblast-like cells. A study in P2X(7) receptor knockout mice suggested the involvement of these receptors in bone formation. We have investigated the expression and pharmacology of several P2X receptors in two human osteosarcoma cell lines to see if they could be involved in bone turnover in man. EXPERIMENTAL APPROACH: Reverse transcriptase-polymerase chain reaction and Western blotting were used to study P2X(2), P2X(4) and P2X(7) receptor expression at mRNA and protein levels, respectively, in human osteoblast-like cells. P2X(7) receptor pharmacology was studied by measuring pore formation in the presence of different agonists and antagonists using the YO-PRO 1 uptake method. KEY RESULTS: P2X(4) and P2X(7) receptor mRNA and protein were found to be expressed by these cell lines. No evidence was found for P2X(4)/P2X(7) receptor heteropolymerization. 2'-3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (DBzATP) was equipotent to ATP and the antagonists used were either ineffective or weakly blocked pore formation. CONCLUSIONS AND IMPLICATIONS: This study demonstrates that P2X(4) and P2X(7) receptors are expressed by human osteoblast-like cells. The affinities of the different agonists suggest that the P2X(7) receptor is mainly responsible for pore formation although P2X(4) receptors may also be involved. The low affinity of DBzATP and the weak action of the antagonists support the previously described atypical pharmacology of the P2X(7) receptor in osteoblasts. Targeting the P2X(7) receptor in osteoblasts could represent a promising new treatment for bone diseases such as osteoporosis and rheumatoid arthritis.
BACKGROUND AND PURPOSE: The expression and function of P2X(7) receptors in osteoclasts is well established, but less is known about their role in osteoblast-like cells. A study in P2X(7) receptor knockout mice suggested the involvement of these receptors in bone formation. We have investigated the expression and pharmacology of several P2X receptors in two humanosteosarcoma cell lines to see if they could be involved in bone turnover in man. EXPERIMENTAL APPROACH: Reverse transcriptase-polymerase chain reaction and Western blotting were used to study P2X(2), P2X(4) and P2X(7) receptor expression at mRNA and protein levels, respectively, in human osteoblast-like cells. P2X(7) receptor pharmacology was studied by measuring pore formation in the presence of different agonists and antagonists using the YO-PRO 1 uptake method. KEY RESULTS:P2X(4) and P2X(7) receptor mRNA and protein were found to be expressed by these cell lines. No evidence was found for P2X(4)/P2X(7) receptor heteropolymerization. 2'-3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (DBzATP) was equipotent to ATP and the antagonists used were either ineffective or weakly blocked pore formation. CONCLUSIONS AND IMPLICATIONS: This study demonstrates that P2X(4) and P2X(7) receptors are expressed by human osteoblast-like cells. The affinities of the different agonists suggest that the P2X(7) receptor is mainly responsible for pore formation although P2X(4) receptors may also be involved. The low affinity of DBzATP and the weak action of the antagonists support the previously described atypical pharmacology of the P2X(7) receptor in osteoblasts. Targeting the P2X(7) receptor in osteoblasts could represent a promising new treatment for bone diseases such as osteoporosis and rheumatoid arthritis.
Authors: B S Khakh; G Burnstock; C Kennedy; B F King; R A North; P Séguéla; M Voigt; P P Humphrey Journal: Pharmacol Rev Date: 2001-03 Impact factor: 25.468
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Authors: F Di Virgilio; P Chiozzi; D Ferrari; S Falzoni; J M Sanz; A Morelli; M Torboli; G Bolognesi; O R Baricordi Journal: Blood Date: 2001-02-01 Impact factor: 22.113
Authors: E Nakamura; Y Uezono; K Narusawa; I Shibuya; Y Oishi; M Tanaka; N Yanagihara; T Nakamura; F Izumi Journal: Am J Physiol Cell Physiol Date: 2000-08 Impact factor: 4.249
Authors: M Solle; J Labasi; D G Perregaux; E Stam; N Petrushova; B H Koller; R J Griffiths; C A Gabel Journal: J Biol Chem Date: 2001-01-05 Impact factor: 5.157
Authors: Ulf Thunberg; Gerard Tobin; Anna Johnson; Ola Söderberg; Leonid Padyukov; Magnus Hultdin; Lars Klareskog; Gunilla Enblad; Christer Sundström; Göran Roos; Richard Rosenquist Journal: Lancet Date: 2002-12-14 Impact factor: 79.321
Authors: Andrea Brandao-Burch; Michelle L Key; Jessal J Patel; Timothy R Arnett; Isabel R Orriss Journal: Front Endocrinol (Lausanne) Date: 2012-03-19 Impact factor: 5.555