Association between P2X7 Receptor Polymorphisms and Bone Status in Mice
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 differ...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | Journal of Osteoporosis |
| Online Access: | http://dx.doi.org/10.1155/2012/637986 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832564094137270272 |
|---|---|
| author | Susanne Syberg Peter Schwarz Solveig Petersen Thomas H. Steinberg Jens-Erik Beck Jensen Jenni Teilmann Niklas Rye Jørgensen |
| author_facet | Susanne Syberg Peter Schwarz Solveig Petersen Thomas H. Steinberg Jens-Erik Beck Jensen Jenni Teilmann Niklas Rye Jørgensen |
| author_sort | Susanne Syberg |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ecf330bba2b646d69b8eb3f79dfc512f |
| institution | Kabale University |
| issn | 2090-8059 2042-0064 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Osteoporosis |
| spelling | doaj-art-ecf330bba2b646d69b8eb3f79dfc512f2025-02-03T01:11:54ZengWileyJournal of Osteoporosis2090-80592042-00642012-01-01201210.1155/2012/637986637986Association between P2X7 Receptor Polymorphisms and Bone Status in MiceSusanne Syberg0Peter Schwarz1Solveig Petersen2Thomas H. Steinberg3Jens-Erik Beck Jensen4Jenni Teilmann5Niklas Rye Jørgensen6Research Centre of Ageing and Osteoporosis, Departments of Diagnostics and Medicine, Glostrup University Hospital, 2600 Glostrup, DenmarkResearch Centre of Ageing and Osteoporosis, Departments of Diagnostics and Medicine, Glostrup University Hospital, 2600 Glostrup, DenmarkResearch Centre of Ageing and Osteoporosis, Departments of Diagnostics and Medicine, Glostrup University Hospital, 2600 Glostrup, DenmarkDepartment of Internal Medicine, Washington University School of Medicine and the St. Louis Veterans Affairs Medical Center, St. Louis, MO 63110, USAOsteoporosis and Bone Metabolic Unit, Departments of Endocrinology and Clinical Biochemistry, Hvidovre University Hospital, 2650 Hvidovre, DenmarkOsteoporosis and Bone Metabolic Unit, Departments of Endocrinology and Clinical Biochemistry, Hvidovre University Hospital, 2650 Hvidovre, DenmarkResearch Centre of Ageing and Osteoporosis, Departments of Diagnostics and Medicine, Glostrup University Hospital, 2600 Glostrup, DenmarkMacrophages 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.http://dx.doi.org/10.1155/2012/637986 |
| spellingShingle | Susanne Syberg Peter Schwarz Solveig Petersen Thomas H. Steinberg Jens-Erik Beck Jensen Jenni Teilmann Niklas Rye Jørgensen Association between P2X7 Receptor Polymorphisms and Bone Status in Mice Journal of Osteoporosis |
| title | Association between P2X7 Receptor Polymorphisms and Bone Status in Mice |
| title_full | Association between P2X7 Receptor Polymorphisms and Bone Status in Mice |
| title_fullStr | Association between P2X7 Receptor Polymorphisms and Bone Status in Mice |
| title_full_unstemmed | Association between P2X7 Receptor Polymorphisms and Bone Status in Mice |
| title_short | Association between P2X7 Receptor Polymorphisms and Bone Status in Mice |
| title_sort | association between p2x7 receptor polymorphisms and bone status in mice |
| url | http://dx.doi.org/10.1155/2012/637986 |
| work_keys_str_mv | AT susannesyberg associationbetweenp2x7receptorpolymorphismsandbonestatusinmice AT peterschwarz associationbetweenp2x7receptorpolymorphismsandbonestatusinmice AT solveigpetersen associationbetweenp2x7receptorpolymorphismsandbonestatusinmice AT thomashsteinberg associationbetweenp2x7receptorpolymorphismsandbonestatusinmice AT jenserikbeckjensen associationbetweenp2x7receptorpolymorphismsandbonestatusinmice AT jenniteilmann associationbetweenp2x7receptorpolymorphismsandbonestatusinmice AT niklasryejørgensen associationbetweenp2x7receptorpolymorphismsandbonestatusinmice |