UNLABELLED: Using human peripheral blood mononuclear cells as osteoclast precursors, we showed that dexamethasone stimulated osteoclast generation at a pharmacological concentration but did not affect the life span of human osteoclasts. Dexamethasone also dose-dependently increased signals for osteoclastogenesis. INTRODUCTION: Glucocorticoid-induced osteoporosis is a common and serious disease. Glucocorticoids predominantly affect osteoblast proliferation and life span. Much of the bone loss is caused by reduced bone formation, but there is also an element of increased bone resorption. MATERIALS AND METHODS: Human peripheral blood mononuclear cells were cultured on whale dentine and induced to differentiate to osteoclasts by RANKL and human macrophage-colony stimulating factor (M-CSF). Osteoclast activity was quantified by pit area. RANKL and osteoprotegerin (OPG) expression in osteoblasts were measured by real-time RT-PCR. RESULTS: In the early phase of osteoclast generation (0-16 days), cultures from two different donors showed that dexamethasone at 10(-8) M increased pit area by 2.5-fold, whereas lower concentrations had no effect. At the highest dexamethasone concentration (10(-7) M), pit area was reduced. In 21-day cultures from three other donors, a similar increase was seen with dexamethasone at 10(-8) M. There was, however, no evidence of increased life span of osteoclasts with dexamethasone. In human primary osteoblasts, dexamethasone dose-dependently reduced OPG and increased RANKL expression as measured by quantitative real time RT-PCR. CONCLUSION: These data provide some explanation at a cellular and molecular level for the observed increase in bone resorption seen in patients treated with glucocorticoids and indicate that there are clear direct effects of glucocorticoids on bone resorption in human cell systems that may differ from other species.
UNLABELLED: Using human peripheral blood mononuclear cells as osteoclast precursors, we showed that dexamethasone stimulated osteoclast generation at a pharmacological concentration but did not affect the life span of human osteoclasts. Dexamethasone also dose-dependently increased signals for osteoclastogenesis. INTRODUCTION: Glucocorticoid-induced osteoporosis is a common and serious disease. Glucocorticoids predominantly affect osteoblast proliferation and life span. Much of the bone loss is caused by reduced bone formation, but there is also an element of increased bone resorption. MATERIALS AND METHODS:Human peripheral blood mononuclear cells were cultured on whale dentine and induced to differentiate to osteoclasts by RANKL and humanmacrophage-colony stimulating factor (M-CSF). Osteoclast activity was quantified by pit area. RANKL and osteoprotegerin (OPG) expression in osteoblasts were measured by real-time RT-PCR. RESULTS: In the early phase of osteoclast generation (0-16 days), cultures from two different donors showed that dexamethasone at 10(-8) M increased pit area by 2.5-fold, whereas lower concentrations had no effect. At the highest dexamethasone concentration (10(-7) M), pit area was reduced. In 21-day cultures from three other donors, a similar increase was seen with dexamethasone at 10(-8) M. There was, however, no evidence of increased life span of osteoclasts with dexamethasone. In human primary osteoblasts, dexamethasone dose-dependently reduced OPG and increased RANKL expression as measured by quantitative real time RT-PCR. CONCLUSION: These data provide some explanation at a cellular and molecular level for the observed increase in bone resorption seen in patients treated with glucocorticoids and indicate that there are clear direct effects of glucocorticoids on bone resorption in human cell systems that may differ from other species.
Authors: Tara C Brennan-Speranza; Holger Henneicke; Sylvia J Gasparini; Katharina I Blankenstein; Uta Heinevetter; Victoria C Cogger; Dmitri Svistounov; Yaqing Zhang; Gregory J Cooney; Frank Buttgereit; Colin R Dunstan; Caren Gundberg; Hong Zhou; Markus J Seibel Journal: J Clin Invest Date: 2012-10-24 Impact factor: 14.808