Apelin and its receptor are expressed in human osteoblasts.
OBJECTIVE
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.
Xie
Hui
H
Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University, 139# Middle Renmin Road, Changsha, Hunan, 410011, PR China.
Tang
Si-yuan
SY
Cui
Rong-rong
RR
Huang
Jiao
J
Ren
Xiao-hong
XH
Yuan
Ling-qing
LQ
Lu
Ying
Y
Yang
Min
M
Zhou
Hou-de
HD
Wu
Xian-ping
XP
Luo
Xiang-hang
XH
Liao
Er-yuan
EY
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000073861:Apelin; D000075244:Apelin Receptors; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D024042:Collagen Type I / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects
C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D002867:Chromones; D024042:Collagen Type I; D036341:Intercellular Signaling Peptides and Proteins; D009025:Morpholines; D043562:Receptors, G-Protein-Coupled; D015675:Osteocalcin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000469:Alkaline Phosphatase