Involvement of small G protein RhoB in the regulation of proliferation, adhesion and migration by dexamethasone in osteoblastic cells.
Long-term exposure to therapeutic doses of glucocorticoids (GCs) results in bone remodeling, which frequently causes osteoporosis and fracture healing retardation because of the abnormality of osteoblastic proliferation and differentiation. The mechanisms of GCs' effect on osteoblasts are largely unknown. In this present study, we found that dexamethasone (Dex) could induce the expression of the small G protein, RhoB, in mRNA and protein levels in the osteoblast-derived osteosarcoma cell lines MG-63. The up-regulation of RhoB mRNA by Dex mainly occurs at posttranscriptional level by increasing its mRNA stability through PI-3K/Akt and p38 mitogen-activated protein kinase signaling pathways. Over-expression of RhoB in MG-63 cells magnified while down-regulation of RhoB level by RNA interference impaired Dex-induced growth inhibition but not differentiation. What's more, over-expression of RhoB mimicked the effect of Dex on cell adhesion and migration. And interfering RhoB expression partially suppressed Dex-induced pro-adhesion and anti-migration in MG-63 cells. In conclusion, these results indicate that RhoB plays an important role in the pathological effect of Dex on osteoblastic growth and migration, which is a part of the mechanisms of GCs' adverse effect on bone remodeling.
Department of Pathophysiology, Second Military Medical University, Shanghai, China.
Fei
F
Diao
Department of Orthopedics, Changhai Hospital affiliated to Second Military Medical University, Shanghai, China.|Department of -Orthopedics, Fuzhou Second Hospital affiliated to Xiamen University, Fuzhou, Fujian Province, China.
Kangyao
K
Chen
Department of Pathophysiology, Second Military Medical University, Shanghai, China.
Yan
Y
Wang
Department of Pathophysiology, Second Military Medical University, Shanghai, China.
Yidong
Y
Li
Department of Orthopedics, Changhai Hospital affiliated to Second Military Medical University, Shanghai, China.
Weidong
W
Xu
Department of Pathophysiology, Second Military Medical University, Shanghai, China.
Jian
J
Lu
Department of Pathophysiology, Second Military Medical University, Shanghai, China.
Yu-Xia
http://orcid.org/0000-0003-0665-3208
YX
Chen
D001846:Bone Development / Q000187:drug effects*; D016723:Bone Remodeling / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D003907:Dexamethasone; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D020743:rhoB GTP-Binding Protein