Endocr J. 2010;57(5):455-62. Epub 2010 Feb 20.
- Glucocorticoid-induced gene tripartite motif-containing 63 (TRIM63) promotes differentiation of osteoblastic cells. Azuma K, et al. Endocr J, 2010. PMID 20173306
Glucocorticoid-induced gene tripartite motif-containing 63 (TRIM63) promotes differentiation of osteoblastic cells.
Abstract
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.
- PMID:
- 20173306
- [Indexed for MEDLINE]
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