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.

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.