[Frontiers in Bioscience 16, 2572-2585, June 1, 2011]
Role of purinergic receptor polymorphisms in human bone
Anke Wesselius1, Martijn J.L. Bours1, Ankita Agrawal2, Alison Gartland2, Pieter C. Dagnelie1, Peter Schwarz3,4, Niklas R. Jorgensen3
1University of Maastricht, Department of Epidemiology, School for Public Health and Primary Care (CAPHRI) , P.O. Box 616, 6200 MD, Maastricht, The Netherlands, 2The Mellanby Centre for Bone Research, Dept. Human Metabolism, The University of Sheffield, S10 2RX, UK, 3University Hospital of Copenhagen Glostrup , Research Center for Ageing and Osteoporosis and Dept. of Clinical Chemistry, Glostrup, Ndr Ringvej 57-59, DK-2600 Glostrup, Denmark, 4Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
TABLE OF CONTENTS
Osteoporosis is a multifactorial disease with a strong genetic component. Variations in a number of genes have been shown to associate with bone turnover and risk of osteoporosis. P2 purinergic receptors are proteins that have ATP or other nucleotides as their natural ligands. Various P2Y and P2X receptor subtypes have been identified on bone cells. Several cellular functions in bone tissue are coupled to P2-receptor activation, including bone resorption, cytokine release, apoptosis, bone formation, and mineral deposition. Furthermore, ATP release and P2 purinergic signalling is a key pathway in the mechanotransductory process, where mechanical stimulation on bone leads to anabolic responses in the skeleton. A number of single nucleotide polymorphisms have been identified in the P2 receptor genes, where especially the P2X7 subtype has been the focus of extensive investigation where several polymorphisms have been shown to have functional implications on receptor function; moreover, some polymorphisms are associated with alterations in bone turnover and bone mass. This review focuses on variations in P2 receptor genes and the association to bone turnover and -quality.