ABSTRACT
Objective To investigate the regulatory effects of glucocorticoids on the local renin-angiotensin system in osteoblasts by using MC3T3-E1 cells.Methods Cellular immune histochemistry was carried out to observe the renin-angiotensin system in osteoblasts.And then after 12-hour culture in serum-free solution,MC3T3-E1 cells were divided into four groups:control,dexamethasone (DXM),dexamethasone + mifepristone (DXM+MIF)and mifepristone (MIF).Components of the renin-angiotensin system including angiotensin type 1 receptor (AT1R),angiotensin type 2 receptor (AT2R)and angiotensin converting enzyme (ACE)in osteoblasts were detected at the mRNA and protein levels using Western blot and PCR.The activity of ACE was also measured after 36-hour intervention.Results The results of immunohistochemistry showed that AT1R,AT2R and ACE were all expressed in osteoblasts.The activity of ACE increased obviously after dexamethasone intervention compared with that in the control group,which was blocked by mifepristone.The mRNA levels of AT1R,AT2R and ACE were increased by dexamethasone compared with those in the control group,which was inhibited by mifepristone.The protein levels of AT1R,AT2R and ACE were enhanced by dexamethasone compared with those in the control group, which was blocked when the cells were co-intervened with mifepristone.However,ACE activity and the mRNA and protein levels of AT1R,AT2R and ACE did not change when the cells were intervened with mifepristone alone (P>0.05).Conclusion The local renin-angiotensin system in osteoblasts is activated by dexamethasone through glucocorticoid receptors on osteoblasts,which may be one of the pathogenesis of glucocorticoid-induced osteoporosis.