RRC ID |
51680
|
著者 |
Saito A, Yoshimura K, Miyamoto Y, Kaneko K, Chikazu D, Yamamoto M, Kamijo R.
|
タイトル |
Enhanced and suppressed mineralization by acetoacetate and β-hydroxybutyrate in osteoblast cultures.
|
ジャーナル |
Biochem Biophys Res Commun
|
Abstract |
It is known that diabetes aggravates alveolar bone loss associated with periodontitis. While insulin depletion increases the blood concentration of ketone bodies, i.e., acetoacetate and β-hydroxybutyrate, their roles in bone metabolism have not been much studied until today. We investigated the effects of acetoacetate and β-hydroxybutyrate on mineralization of extracellular matrix in cultures of mouse osteoblastic MC3T3-E1 cells and primary mouse osteoblasts in the presence and absence of bone morphogenetic protein-2. Acetoacetate potentiated alkaline phosphatase activity in MC3T3-E1 cells in a concentration-dependent manner, ranging from physiological to pathological concentrations (0.05-5 mmol/L). In contrast, β-hydroxybutyrate lowered it in the same experimental settings. Mineralization in cultures of these cells was also up-regulated by acetoacetate and down-regulated by β-hydroxybutyrate. Similar results were obtained in cultures of mouse primary osteoblasts. Neither alkaline phosphatase mRNA nor its protein expression in MC3T3-E1 cells was affected by acetoacetate or β-hydroxybutyrate, indicating that these ketone bodies control the enzyme activity of alkaline phosphatase in osteoblasts and hence their mineralization bi-directionally. Finally, either gene silencing of monocarboxylate transporter-1, a major transmembrate transporter for ketone bodies, nullified the effects of ketone bodies on alkaline phosphatase activity in MC3T3-E1 cells. Collectively, we found that ketone bodies bidirectionally modulates osteoblast functions, which suggests that ketone bodies are important endogenous factors that regulate bone metabolism in both physiological and pathological situations.
|
巻・号 |
473(2)
|
ページ |
537-44
|
公開日 |
2016-4-29
|
DOI |
10.1016/j.bbrc.2016.03.109
|
PII |
S0006-291X(16)30422-3
|
PMID |
27018251
|
MeSH |
3-Hydroxybutyric Acid / metabolism*
Acetoacetates / metabolism*
Alkaline Phosphatase / metabolism*
Animals
Calcification, Physiologic*
Cell Line
Cells, Cultured
Ketone Bodies / metabolism*
Mice
Osteoblasts / cytology
Osteoblasts / metabolism*
|
IF |
2.985
|
引用数 |
4
|
リソース情報 |
ヒト・動物細胞 |
MC3T3-E1(RCB1126) |