Apelin stimulates proliferation and suppresses apoptosis of mouse osteoblastic cell line MC3T3-E1 via JNK and PI3-K/Akt signaling pathways

Peptides. 2007 Mar;28(3):708-18. doi: 10.1016/j.peptides.2006.10.005. Epub 2006 Nov 15.


The aim of this study was to investigate the effects of apelin on proliferation and apoptosis of mouse osteoblastic MC3T3-E1 cells. APJ was expressed in MC3T3-E1 cells. Apelin did not affect Runx2 expression, alkaline phosphatase (ALP) activity, osteocalcin and type I collagen secretion, suggesting that it has no effect on osteoblastic differentiation of MC3T3-E1 cells. However, apelin stimulated MC3T3-E1 cell proliferation and inhibited cell apoptosis induced by serum deprivation. Our study also shows that apelin decreased cytochrome c release and caspase-3, capase-8 and caspase-9 activation in serum-deprived MC3T3-E1 cells. Apelin activated c-Jun N-terminal kinase (JNK) and Akt (phosphatidylinositol 3-kinase downstream effector), and the JNK inhibitor SP600125, the phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 or the Akt inhibitor 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO) inhibited its effects on proliferation and serum deprivation-induced apoptosis. Furthermore, apelin protected against apoptosis induced by the glucocorticoid dexamethasone or TNF-alpha. Apelin stimulates proliferation and suppresses serum deprivation-induced apoptosis of MC3T3-E1 cells and these actions are mediated via JNK and PI3-K/Akt signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipokines
  • Animals
  • Apelin
  • Apelin Receptors
  • Apoptosis / drug effects
  • Carrier Proteins / metabolism
  • Carrier Proteins / pharmacology*
  • Caspases / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Cytochromes c / metabolism
  • Intercellular Signaling Peptides and Proteins
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mice
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Signal Transduction / drug effects


  • Adipokines
  • Apelin
  • Apelin Receptors
  • Apln protein, mouse
  • Aplnr protein, mouse
  • Carrier Proteins
  • Core Binding Factor Alpha 1 Subunit
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Runx2 protein, mouse
  • Cytochromes c
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • JNK Mitogen-Activated Protein Kinases
  • Caspases