Apelin suppresses apoptosis of human osteoblasts

Apoptosis. 2007 Jan;12(1):247-54. doi: 10.1007/s10495-006-0489-7.

Abstract

Objectives: Apelin is a recently discovered peptide that is the endogenous ligand for the orphan G-protein-coupled receptor APJ. Adipocytes can express and secrete apelin. Osteoblast can express apelin and APJ. The aim of this study was to investigate the action of apelin on apoptosis of human osteoblasts.

Results: Apelin inhibited human osteoblasts apoptosis induced by serum deprivation. Suppression of APJ with small-interfering RNA (siRNA) abolished the anti-apoptotic activity of apelin. Our study also showed an increased Bcl-2 protein expression and decreased Bax protein expression under the treatment of apelin. Apelin decreased cytochrome c release and caspase-3 activation in human osteoblasts. Apelin activated phosphatidylinositol-3 kinase (PI-3 kinase) and Akt. The apelin-induced activation of Akt was blocked by suppression of APJ with siRNA. LY294002 (a PI-3 kinase inhibitor) or 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO; an Akt inhibitor) abolished apelin induced activation of Akt, and, LY294002 or HIMO abolished the anti-apoptotic activity of apelin. Furthermore, apelin protects against apoptosis induced by the glucocorticoid dexamethasone.

Conclusions: Apelin suppresses serum deprivation-induced apoptosis of human osteoblasts and the anti-apoptotic action is mediated via the APJ/PI-3 kinase/Akt signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apelin
  • Apelin Receptors
  • Apoptosis / drug effects*
  • Base Sequence
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / genetics
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / genetics
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects

Substances

  • APLN protein, human
  • APLNR protein, human
  • Apelin
  • Apelin Receptors
  • Intercellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled
  • Recombinant Proteins
  • Dexamethasone
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt