title: The inhibitory effect of bisphosphonates on glucocorticoid-induced RANKL expression in human cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Second Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kobayashi
authors.forename: F
authors.initials: F
authors.lastname: Hirano
authors.forename: I
authors.initials: I
authors.lastname: Makino
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; D002352:Carrier Proteins; D004164:Diphosphonates; D005938:Glucocorticoids; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D003907:Dexamethasone