Apelin and its receptor are expressed in human osteoblasts

Regul Pept. 2006 May 15;134(2-3):118-25. doi: 10.1016/j.regpep.2006.02.004. Epub 2006 Mar 6.


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. The aim of this study was to characterize apelin and APJ expression in human osteoblasts and to investigate the effects of apelin on osteoblasts.

Results: Apelin and APJ were expressed in human osteoblasts. Apelin stimulated proliferation of human osteoblasts, but had no effect on alkaline phosphatase (ALP) activity, osteocalcin and type I collagen production in human osteoblasts. Suppression of APJ with small-interfering RNA (siRNA) abolished the apelin-induced cell proliferation. Apelin induced activation of Akt (Phosphatidylinositol-3 kinase downstream effector), but not MAPKs, such as c-jun N-terminal Kinase (JNK), p38 and ERK1/2 in human osteoblasts. This effect was blocked by suppression of APJ with siRNA. Furthermore, LY294002 (PI3 kinase inhibitor) blocked the activation of Akt by apelin and abolished the apelin-induced cell proliferation.

Conclusions: Human osteoblasts express apelin and APJ and apelin enhances human osteoblast proliferation, but has no effect on osteoblast differentiation, and APJ/PI3 kinase/Akt pathway is involved in the proliferation response. These findings suggest that apelin may function as a mitogenic agent for osteoblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alkaline Phosphatase / metabolism
  • Apelin
  • Apelin Receptors
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chromones / pharmacology
  • Collagen Type I / metabolism
  • Gene Expression
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Middle Aged
  • Morpholines / pharmacology
  • Osteoblasts / metabolism*
  • Osteocalcin / metabolism
  • Phosphatidylinositol 3-Kinases / physiology
  • Proto-Oncogene Proteins c-akt / physiology
  • Receptors, G-Protein-Coupled / biosynthesis*
  • Signal Transduction / drug effects


  • APLN protein, human
  • APLNR protein, human
  • Apelin
  • Apelin Receptors
  • Chromones
  • Collagen Type I
  • Intercellular Signaling Peptides and Proteins
  • Morpholines
  • Receptors, G-Protein-Coupled
  • Osteocalcin
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Alkaline Phosphatase