RRC ID 42526
Author Kobayashi A, Hirano F, Makino I.
Title The inhibitory effect of bisphosphonates on glucocorticoid-induced RANKL expression in human cells.
Journal Scand J Rheumatol
Abstract OBJECTIVE:RANKL is known to play an important role in activating osteoclasts and advancing the progress of osteoporosis. However, little is known about the effect of bisphosphonates on glucocorticoid-induced RANKL expression in human cells. Our study was intended to clarify effects of bisphosphonates on glucocorticoid-induced RANKL expression in human cells.
METHODS:Human T lymphoblastic cell line Jurkat and human osteosarcoma cell line MG-63 were used for the following experiments. RANKL expression in two cell lines was measured using reverse transcription polymerase chain reaction (RT-PCR) analysis and enzyme immunoassay (EIA). Luciferase assays using pGRE-Luc were also performed.
RESULTS:In Jurkat and MG-63 cells, dexamethasone induced expression of soluble RANKL (sRANKL) protein in supernatants and RANKL mRNA in cells. Moreover, bisphosphonates, but not cyclooxygenase inhibitors, repressed dexamethasone-induced sRANKL protein production. By contrast, glucocorticoid receptor-driven transcriptional activity was not inhibited by bisphosphonates.
CONCLUSION:Glucocorticoid induced RANKL expression in human cells derived from T lymphocytes and osteoblasts. Bisphosphonates inhibited glucocorticoid-induced RANKL expression, suggesting that these effects might be a new therapeutic mechanism for bisphosphonates.
Volume 34(6)
Pages 480-4
Published 2005-1-1
DOI 10.1080/03009740510026788
PII P414M54P635Q8103
PMID 16393773
MeSH Anti-Inflammatory Agents / pharmacology Bone Density Conservation Agents / pharmacology* Carrier Proteins / genetics* Carrier Proteins / metabolism Dexamethasone / pharmacology* Diphosphonates / pharmacology* Gene Expression / drug effects Glucocorticoids / pharmacology* Humans Jurkat Cells / drug effects Jurkat Cells / metabolism Membrane Glycoproteins / genetics* Membrane Glycoproteins / metabolism Osteoblasts / drug effects Osteoblasts / metabolism Osteosarcoma / drug therapy Osteosarcoma / metabolism RANK Ligand RNA, Messenger / metabolism Receptor Activator of Nuclear Factor-kappa B Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes / drug effects T-Lymphocytes / metabolism
IF 3.025
Times Cited 13
WOS Category RHEUMATOLOGY
Resource
Human and Animal Cells MG‐63(RCB1890)