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)