RRC ID |
36849
|
著者 |
Okito A, Nakahama K, Akiyama M, Ono T, Morita I.
|
タイトル |
Involvement of the G-protein-coupled receptor 4 in RANKL expression by osteoblasts in an acidic environment.
|
ジャーナル |
Biochem Biophys Res Commun
|
Abstract |
Osteoclast activity is enhanced in acidic environments following systemic or local inflammation. However, the regulatory mechanism of receptor activator of NF-κB ligand (RANKL) expression in osteoblasts under acidic conditions is not fully understood. In the present paper, we detected the mRNA expression of the G-protein-coupled receptor (GPR) proton sensors GPR4 and GPR65 (T-cell death-associated gene 8, TDAG8), in osteoblasts. RANKL expression and the cyclic AMP (cAMP) level in osteoblasts were up-regulated under acidic culture conditions. Acidosis-induced up-regulation of RANKL was abolished by the protein kinase A inhibitor H89. To clarify the role of GPR4 in RANKL expression, GPR4 gain and loss of function experiments were performed. Gene knockdown and forced expression of GPR4 caused reduction and induction of RANKL expression, respectively. These results suggested that, at least in part, RANKL expression by osteoblasts in an acidic environment was mediated by cAMP/PKA signaling resulting from GPR4 activation. A comprehensive microarray analysis of gene expression of osteoblasts revealed that, under acidic conditions, the phenotype of osteoblasts was that of an osteoclast supporting cell rather than that of a mineralizing cell. These findings will contribute to a molecular understanding of bone disruption in an acidic environment.
|
巻・号 |
458(2)
|
ページ |
435-40
|
公開日 |
2015-3-6
|
DOI |
10.1016/j.bbrc.2015.01.142
|
PII |
S0006-291X(15)00189-8
|
PMID |
25668130
|
MeSH |
Animals
Cells, Cultured
Hydrogen-Ion Concentration*
Mice
Osteoblasts / chemistry*
Osteoblasts / cytology
Osteoblasts / metabolism*
RANK Ligand / metabolism*
Receptors, G-Protein-Coupled / metabolism*
|
IF |
2.985
|
引用数 |
9
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
MC3T3-E1(RCB1126) |