TY - JOUR
T1 - Association between P2X7 Receptor Polymorphisms and Bone Status in Mice
AU - Syberg, Susanne
AU - Schwarz, Peter
AU - Petersen, Solveig
AU - Steinberg, Thomas H
AU - Jensen, Jens-Erik Beck
AU - Teilmann, Jenni
AU - Jørgensen, Niklas Rye
PY - 2012
Y1 - 2012
N2 - Macrophages from mouse strains with the naturally occurring mutation P451L in the purinergic receptor P2X7 have impaired responses to agonists (1). Because P2X7 receptors are expressed in bone cells and are implicated in bone physiology, we asked whether strains with the P451L mutation have a different bone phenotype. By sequencing the most common strains of inbred mice, we found that only a few strains (BALB, NOD, NZW, and 129) were harboring the wild allelic version of the mutation (P451) in the gene for the purinergic receptor P2X7. The strains were compared by means of dual energy X-ray absorptiometry (DXA), bone markers, and three-point bending. Cultured osteoclasts were used in the ATP-induced pore formation assay. We found that strains with the P451 allele (BALB/cJ and 129X1/SvJ) had stronger femurs and higher levels of the bone resorption marker C-telopeptide collagen (CTX) compared to C57Bl/6 (B6) and DBA/2J mice. In strains with the 451L allele, pore-formation activity in osteoclasts in vitro was lower after application of ATP. In conclusion, two strains with the 451L allele of the naturally occurring mutation P451L, have weaker bones and lower levels of CTX, suggesting lower resorption levels in these animals, which could be related to the decreased ATP-induced pore formation observed in vitro. The importance of these findings for the interpretation of the earlier reported effects of P2X7 in mice is discussed, along with strategies in developing a murine model for testing the therapeutic effects of P2X7 agonists and antagonists upon postmenopausal osteoporosis.
AB - Macrophages from mouse strains with the naturally occurring mutation P451L in the purinergic receptor P2X7 have impaired responses to agonists (1). Because P2X7 receptors are expressed in bone cells and are implicated in bone physiology, we asked whether strains with the P451L mutation have a different bone phenotype. By sequencing the most common strains of inbred mice, we found that only a few strains (BALB, NOD, NZW, and 129) were harboring the wild allelic version of the mutation (P451) in the gene for the purinergic receptor P2X7. The strains were compared by means of dual energy X-ray absorptiometry (DXA), bone markers, and three-point bending. Cultured osteoclasts were used in the ATP-induced pore formation assay. We found that strains with the P451 allele (BALB/cJ and 129X1/SvJ) had stronger femurs and higher levels of the bone resorption marker C-telopeptide collagen (CTX) compared to C57Bl/6 (B6) and DBA/2J mice. In strains with the 451L allele, pore-formation activity in osteoclasts in vitro was lower after application of ATP. In conclusion, two strains with the 451L allele of the naturally occurring mutation P451L, have weaker bones and lower levels of CTX, suggesting lower resorption levels in these animals, which could be related to the decreased ATP-induced pore formation observed in vitro. The importance of these findings for the interpretation of the earlier reported effects of P2X7 in mice is discussed, along with strategies in developing a murine model for testing the therapeutic effects of P2X7 agonists and antagonists upon postmenopausal osteoporosis.
U2 - 10.1155/2012/637986
DO - 10.1155/2012/637986
M3 - Journal article
C2 - 22919543
SN - 2042-0064
VL - 2012
SP - 637986
JO - Journal of Osteoporosis
JF - Journal of Osteoporosis
ER -