Glucocorticoids exert their function by regulating
glucocorticoid-responsive genes through interaction with
glucocorticoid receptor alpha (
GRalpha), a
nuclear receptor.
Glucocorticoids also affect bone metabolism; this is evidenced by the fact that
GRalpha is expressed in several kinds of cells in bone tissue, including osteoblasts, osteocytes, osteoclasts, mononuclear cells in bone marrow, and hypertrophic chondrocytes.
Glucocorticoids are known to induce osteoblastic differentiation and bone formation. However, this effect of
glucocorticoids on bone tissue is still controversial since long-term use of
glucocorticoids results in
osteoporosis in vivo. To identify
glucocorticoid-regulated genes in human osteoblastic cells, SaOS2 cells were treated with
dexamethasone (10(-8) M) for 6 hours, and were then subjected to microarray analysis. Genes such as C/EBPdelta, DUSP1, Per1 and TRIM63 were found to be induced by
dexamethasone. The induction of mRNAs of these genes by
dexamethasone (10(-8) M, 10(-7) M, and 10(-6) M) was confirmed by quantitative real-time polymerase chain reaction (PCR). TRIM63, also called muscle-specific ring finger
protein 1 (MuRF1), was reported to be an
E3 ubiquitin ligase expressed mainly in muscular tissue. SaOS2 cells overexpressing exogenous TRIM63 showed increased expression of an osteoblastic
differentiation marker gene,
alkaline phosphatase, with reduced proliferation. These results suggest that TRIM63 is a candidate for genes mediating the
glucocorticoid-induced promotion of osteoblastic differentiation.