Activation of FGF receptors is a new mechanism by which strontium ranelate induces osteoblastic cell growth.
- Caverzasio J Service of Bone Diseases, Department of Rehabilitation and Geriatrics, University Hospital of Geneva, Geneva, Switzerland. Joseph.Caverzasio@unige.ch
- Thouverey C
- 2011-04-08
Published in:
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. - 2011
Animals
Bone Density Conservation Agents
Cell Proliferation
Cells, Cultured
Membrane Proteins
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Organometallic Compounds
Osteoblasts
Proto-Oncogene Proteins c-akt
Receptors, Calcium-Sensing
Receptors, Fibroblast Growth Factor
Signal Transduction
Thiophenes
p38 Mitogen-Activated Protein Kinases
English
BACKGROUND/AIMS
Strontium ranelate (SrRan) is an anti-osteoporotic treatment that reduces the risk of vertebral and hip fractures. Recent in vitro studies suggest that the effect of strontium ranelate on osteoblastic cell growth likely involves two processes including activation of the calcium sensing receptor (CaSR) and a yet undefined mechanism. In the present study, we investigated the CaSR-independent molecular mechanism by which SrRan stimulates osteoblast growth.
METHODS
MC3T3-E1 and primary osteoblastic cells, specific inhibitors of receptor tyrosine kinases (RTK) and western blot analysis were used to characterize the CaSR-independent mechanism in osteoblastic cells.
RESULTS
A selective inhibitor of FGF receptor but not other RTK inhibitors markedly blunted cell growth induced by SrRan in osteoblastic cells. Associated with this observation, SrRan induced rapid activation of FGFR signaling pathways such as PLCγ, FRS2, Akt, ERK1,2 and p38. FGFR-dependent stimulation of osteogenic cell growth was also observed with other cations but not with neomycin, a selective CaSR agonist. Also, in cultured conditions used in this study, MC3T3-E1 cells and primary osteoblasts did not express the CaSR.
CONCLUSION
data presented in this study suggest that activation of FGFRs is a new potential mechanism by which strontium can stimulate osteoblastic cell growth. Activation of FGFR-dependent cell growth is also observed in response to other cations suggesting that activation of FGF receptors is a new cation sensing mechanism in osteoblasts.
Strontium ranelate (SrRan) is an anti-osteoporotic treatment that reduces the risk of vertebral and hip fractures. Recent in vitro studies suggest that the effect of strontium ranelate on osteoblastic cell growth likely involves two processes including activation of the calcium sensing receptor (CaSR) and a yet undefined mechanism. In the present study, we investigated the CaSR-independent molecular mechanism by which SrRan stimulates osteoblast growth.
METHODS
MC3T3-E1 and primary osteoblastic cells, specific inhibitors of receptor tyrosine kinases (RTK) and western blot analysis were used to characterize the CaSR-independent mechanism in osteoblastic cells.
RESULTS
A selective inhibitor of FGF receptor but not other RTK inhibitors markedly blunted cell growth induced by SrRan in osteoblastic cells. Associated with this observation, SrRan induced rapid activation of FGFR signaling pathways such as PLCγ, FRS2, Akt, ERK1,2 and p38. FGFR-dependent stimulation of osteogenic cell growth was also observed with other cations but not with neomycin, a selective CaSR agonist. Also, in cultured conditions used in this study, MC3T3-E1 cells and primary osteoblasts did not express the CaSR.
CONCLUSION
data presented in this study suggest that activation of FGFRs is a new potential mechanism by which strontium can stimulate osteoblastic cell growth. Activation of FGFR-dependent cell growth is also observed in response to other cations suggesting that activation of FGF receptors is a new cation sensing mechanism in osteoblasts.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1159/000327950
- PMID 21471713
- Persistent URL
- https://sonar.ch/global/documents/245310
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