Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway.
Adipocytes can highly and specifically express adiponectin, and the adiponectin receptor (AdipoR) has been detected in bone-forming cells. The present study was undertaken to investigate the action of adiponectin on osteoblast proliferation and differentiation. AdipoR1 protein was detected in human osteoblasts. Adiponectin promoted osteoblast proliferation and resulted in a dose- and time-dependent increase in alkaline phosphatase (ALP) activity, osteocalcin and type I collagen production, and an increase in mineralized matrix. Suppression of AdipoR1 with small-interfering RNA (siRNA) abolished the adiponectin-induced cell proliferation and ALP expression. Adiponectin induces activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal Kinase (JNK), but not ERK1/2 in osteoblasts, and these effects were blocked by suppression of AdipoR1 with siRNA. Furthermore, pretreatment of osteoblasts with the JNK inhibitor SP600125 abolished the adiponectin-induced cell proliferation. p38 inhibitor SB203580 blocked the adiponectin-induced ALP activity. These data indicate that adiponectin induces human osteoblast proliferation and differentiation, and the proliferation response is mediated by the AdipoR/JNK pathway, while the differentiation response is mediated via the AdipoR/p38 pathway. These findings suggest that osteoblasts are the direct targets of adiponectin.
Luo
Xiang-Hang
XH
Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University, 86 Middle Renmin Road, Changsha, Hunan 410011, PR China.
Guo
Li-Juan
LJ
Yuan
Ling-Qing
LQ
Xie
Hui
H
Zhou
Hou-De
HD
Wu
Xian-Ping
XP
Liao
Er-Yuan
EY
D052242:Adiponectin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000819:agonists / Q000502:physiology
D052242:Adiponectin; D011956:Receptors, Cell Surface; D048031:JNK Mitogen-Activated Protein Kinases