The Calcium-sensing Receptor Is Involved in Strontium Ranelate-induced Osteoclast Apoptosis
| Autor: | Romuald Mentaverri, Michel Brazier, Alice Wattel, Edward M. Brown, Axelle Caudrillier, Ernest F. Terwilliger, Anne S. Hurtel-Lemaire, Fabienne Cournarie, Said Kamel |
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| Rok vydání: | 2009 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Chemistry Protein Kinase C beta Cell Biology Biochemistry Bone resorption Cell biology Endocrinology medicine.anatomical_structure Strontium ranelate Osteoclast Apoptosis Internal medicine Bone cell medicine Calcium-sensing receptor Signal transduction Molecular Biology medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 284:575-584 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m801668200 |
| Popis: | Strontium ranelate exerts both an anti-catabolic and an anabolic effect on bone cells. To further investigate the molecular mechanism whereby strontium ranelate inhibits bone resorption, we focused our attention on the effects of strontium ranelate on osteoclast apoptosis and on the underlying mechanism(s). Using primary mature rabbit osteoclasts, we demonstrated that strontium (Sro2+) dose-dependently stimulates the apoptosis of mature osteoclasts. As shown previously for calcium (Cao2+), the Sro2+-induced effect on mature osteoclasts is mediated by the Cao2+-sensing receptor, CaR, which in turn stimulates a phospholipase C-dependent signaling pathway and nuclear translocation of NF-kappaB. Unlike Cao2+, however, Sro2+-induced osteoclast apoptosis was shown to depend on PKCbetaII activation and to be independent of inositol 1,4,5-trisphosphate action. As a consequence of these differences in their intracellular signaling pathways, Sro2+ and Cao2+ in combination were shown to exert a greater effect on mature osteoclast apoptosis than did either divalent cation by itself. Altogether, our results show that Sro2+ acts through the CaR and induces osteoclast apoptosis through a signaling pathway similar to but different in certain respects from that of Cao2+. This difference in the respective signaling cascades enables Sro2+ to potentiate Cao2+-induced osteoclast apoptosis and vice versa. In this manner, it is conceivable that Sro2+ and Cao2+ act together to inhibit bone resorption in strontium ranelate-treated patients. |
| Databáze: | OpenAIRE |
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