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Effects of calcitonin generelated peptide on osteoprotegerin and RANKL expressions in osteoblast cells in bone metastasis microenvironment of breast cancer in vitro
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Abstract:
Objective:To observe the effect of calcitonin generelated peptide (CGRP) on the expression of osteoprotegerin (OPG) and receptor activator of nuclear factorkappaB ligand (RANKL) in osteoblast cells through an in vitro breast cancer cell and osteoblast cell coculture system.Methods:The metastatic breast cancer MDAMB231 or MDAMB435 cells were cocultured with osteoblast MG63 cells to establish an in vitro microenvironment of bone metastasis of breast cancer. After treated with CGRP(1×108 mol/L), OPG and RANKL mRNA and protein expressions in osteoblast MG63 cells were examined by RTPCR and Western blotting. Results: Expression of RANKL in osteoblast MG63 cells was upregulated at both mRNA and protein levels when osteoblast MG63 cells were cocultured with breast cancer MDAMB231 or MDAMB435 cells, while those of OPG in osteoblast MG63 cells were both downregulated (P<0.05). After treatment with CGRP, expressions of RANKL in osteoblast MG63 cells were downregulated at both mRNA and protein levels, and the expressions of OPG mRNA and protein were both upregulated (P<0.05). Conclusion: Breast cancer MDAMB231 and MDAMB435 cells can promote osteolysis of osteoclast cells via regulating the expression of OPG/RANKL axis in osteoblast cells. CGRP can reverse the osteolysis of osteoblast cells induced by breast cancer cells and may serve as a potential therapeutic agent for treatment of bone metastasis of breast cancer.
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Supported by the Comprehensive Prevention and Treatment Project for Chronic Diseases of Shanghai Municipal Hospitals (No.SHDC12007304)
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