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Apelin attenuates the osteoblastic differentiation of vascular smooth muscle cells.
- Source :
-
PloS one [PLoS One] 2011 Mar 18; Vol. 6 (3), pp. e17938. Date of Electronic Publication: 2011 Mar 18. - Publication Year :
- 2011
-
Abstract
- Vascular calcification, which results from a process osteoblastic differentiation of vascular smooth muscle cells (VSMCs), is a major risk factor for cardiovascular morbidity and mortality. Apelin is a recently discovered peptide that is the endogenous ligand for the orphan G-protein-coupled receptor, APJ. Several studies have identified the protective effects of apelin on the cardiovascular system. However, the effects and mechanisms of apelin on the osteoblastic differentiation of VSMCs have not been elucidated. Using a culture of calcifying vascular smooth muscle cells (CVMSCs) as a model for the study of vascular calcification, the relationship between apelin and the osteoblastic differentiation of VSMCs and the signal pathway involved were investigated. Alkaline phosphatase (ALP) activity and osteocalcin secretion were examined in CVSMCs. The involved signal pathway was studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002, and APJ siRNA. The results showed that apelin inhibited ALP activity, osteocalcin secretion, and the formation of mineralized nodules. APJ protein was detected in CVSMCs, and apelin activated ERK and AKT (a downstream effector of PI3-K). Suppression of APJ with siRNA abolished the apelin-induced activation of ERK and Akt. Furthermore, inhibition of APJ expression, and the activation of ERK or PI3-K, reversed the effects of apelin on ALP activity. These results showed that apelin inhibited the osteoblastic differentiation of CVSMCs through the APJ/ERK and APJ/PI3-K/AKT signaling pathway. Apelin appears to play a protective role against arterial calcification.
- Subjects :
- Apelin Receptors
Calcification, Physiologic drug effects
Cells, Cultured
Extracellular Signal-Regulated MAP Kinases metabolism
Gene Expression Regulation drug effects
Humans
Intracellular Space drug effects
Intracellular Space metabolism
Myocytes, Smooth Muscle enzymology
Osteoblasts drug effects
Osteoblasts metabolism
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt metabolism
Receptors, G-Protein-Coupled genetics
Receptors, G-Protein-Coupled metabolism
Signal Transduction drug effects
Cell Differentiation drug effects
Intercellular Signaling Peptides and Proteins pharmacology
Muscle, Smooth, Vascular cytology
Myocytes, Smooth Muscle cytology
Myocytes, Smooth Muscle drug effects
Osteoblasts cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 6
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 21437254
- Full Text :
- https://doi.org/10.1371/journal.pone.0017938