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Enhanced and suppressed mineralization by acetoacetate and β-hydroxybutyrate in osteoblast cultures
- Source :
- Biochemical and Biophysical Research Communications. 473:537-544
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Biophysics
Ketone Bodies
Biology
Biochemistry
Mineralization (biology)
Acetoacetates
Cell Line
060404 music
Bone remodeling
Extracellular matrix
Mice
03 medical and health sciences
Calcification, Physiologic
Internal medicine
medicine
Animals
3-Hydroxybutyric Acid
Molecular Biology
Cells, Cultured
Osteoblasts
Osteoblast
06 humanities and the arts
Cell Biology
Alkaline Phosphatase
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Cell culture
Ketone bodies
Alkaline phosphatase
0604 arts
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 473
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....e61004cd28b363058325b4fa626b9c33