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Apelin attenuates the osteoblastic differentiation of aortic valve interstitial cells via the ERK and PI3-K/Akt pathways.

Yuan ZS, Zhou YZ, Liao XB, Luo JW, Shen KJ, Hu YR, Gu L, Li JM, Tan CM, Chen HM, Zhou XM - Amino Acids (2015)

Bottom Line: Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies.The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect.These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China.

ABSTRACT
Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs. These cells were used to study the relationship between apelin and the osteoblastic calcification of AVICs and the involved signaling pathways. Alkaline phosphatase (ALP) activity/expression and runt-related transcription factor 2 (Runx2) expression were examined as hallmark proteins in this research. The involved signaling pathways were studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. The results indicate that apelin attenuates the expression and activity of ALP, the expression of Runx2, and the formation of mineralized nodules. This protective effect was dependent on the dose of apelin, reaching the maximum at 100 pM, and was connected to activity of ERK and Akt (a downstream effector of PI3-K). The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect. These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.

No MeSH data available.


Related in: MedlinePlus

The effect of apelin on ALP expression. Human AVICs were induced with PCM containing apelin at different concentrations (0, 10 pM, 100 pM, 1 nM and 10 nM) as well as PD98059 (ERK inhibitor) and LY29402 (Akt inhibitor) for 14 days
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Fig3: The effect of apelin on ALP expression. Human AVICs were induced with PCM containing apelin at different concentrations (0, 10 pM, 100 pM, 1 nM and 10 nM) as well as PD98059 (ERK inhibitor) and LY29402 (Akt inhibitor) for 14 days

Mentions: After stimulating the cells for 14 and 21 days, ALP expression and cell mineralization were strongest (Figs. 2, 3, 4). Figures 2 and 3 show cells treated with normal medium, PCM, and PCM with apelin at 10 pM, 100 pM, 1 nM and 10 nM every other day. In comparison with the blank control and the PCM groups, western blotting showed that apelin decreased the ALP activity and expression dramatically in a dose-dependent manner (Figs. 2a, b, 3) (*P < 0.05 vs. PCM), especially at the concentration of 100 pM. However, this effect was suppressed by PD98059 and LY29402 (#P < 0.05 vs. PCM + 100 pM apelin). Figure 4 shows the result for cells treated with normal medium, PCM and PCM with 100 pM apelin for 21 days every other day. The cell calcification was most obvious in the PCM group, and it was significantly attenuated by apelin in the form of calcium content (*P < 0.05 vs. PCM).Fig. 2


Apelin attenuates the osteoblastic differentiation of aortic valve interstitial cells via the ERK and PI3-K/Akt pathways.

Yuan ZS, Zhou YZ, Liao XB, Luo JW, Shen KJ, Hu YR, Gu L, Li JM, Tan CM, Chen HM, Zhou XM - Amino Acids (2015)

The effect of apelin on ALP expression. Human AVICs were induced with PCM containing apelin at different concentrations (0, 10 pM, 100 pM, 1 nM and 10 nM) as well as PD98059 (ERK inhibitor) and LY29402 (Akt inhibitor) for 14 days
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4633450&req=5

Fig3: The effect of apelin on ALP expression. Human AVICs were induced with PCM containing apelin at different concentrations (0, 10 pM, 100 pM, 1 nM and 10 nM) as well as PD98059 (ERK inhibitor) and LY29402 (Akt inhibitor) for 14 days
Mentions: After stimulating the cells for 14 and 21 days, ALP expression and cell mineralization were strongest (Figs. 2, 3, 4). Figures 2 and 3 show cells treated with normal medium, PCM, and PCM with apelin at 10 pM, 100 pM, 1 nM and 10 nM every other day. In comparison with the blank control and the PCM groups, western blotting showed that apelin decreased the ALP activity and expression dramatically in a dose-dependent manner (Figs. 2a, b, 3) (*P < 0.05 vs. PCM), especially at the concentration of 100 pM. However, this effect was suppressed by PD98059 and LY29402 (#P < 0.05 vs. PCM + 100 pM apelin). Figure 4 shows the result for cells treated with normal medium, PCM and PCM with 100 pM apelin for 21 days every other day. The cell calcification was most obvious in the PCM group, and it was significantly attenuated by apelin in the form of calcium content (*P < 0.05 vs. PCM).Fig. 2

Bottom Line: Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies.The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect.These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China.

ABSTRACT
Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs. These cells were used to study the relationship between apelin and the osteoblastic calcification of AVICs and the involved signaling pathways. Alkaline phosphatase (ALP) activity/expression and runt-related transcription factor 2 (Runx2) expression were examined as hallmark proteins in this research. The involved signaling pathways were studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. The results indicate that apelin attenuates the expression and activity of ALP, the expression of Runx2, and the formation of mineralized nodules. This protective effect was dependent on the dose of apelin, reaching the maximum at 100 pM, and was connected to activity of ERK and Akt (a downstream effector of PI3-K). The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect. These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.

No MeSH data available.


Related in: MedlinePlus