Insulin stimulates osteoblast proliferation and differentiation through ERK and PI3K in MG-63 cells.
Insulin has been proposed to be an anabolic agent in bone, but the mechanisms underlying insulin effects on osteoblast differentiation are still not clear. To explore the mechanisms of action of insulin on osteoblast growth and differentiation, human osteoblastic cell line-MG-63 was used and stimulated by insulin in the presence or absence of ERK inhibitor PD98059, PI3-K inhibitor LY294002, or inhibitor PD98059 + LY294002. The results showed that insulin positively regulated the expression of its receptor. Insulin stimulated the proliferation of MG-63 cells in a time- and dose-dependent manner and blockade of both MAPK and PI3K pathways could inhibit the cell proliferation. In addition, ALP activity, the secretion of type I collagen, OC gene expression, and mineralized nodule formation were increased in the insulin treated group, whereas these indicators were decreased after treatment with blocking agents. However, treatment with PI3-K inhibitor LY294002 significantly reversed the down-regulation of Runx2 expression and treatment with ERK inhibitor PD98059 remarkably decreased up-regulation of Osx and IGF-1 expression after insulin treatment. Therefore, the data obtained from this study suggested that insulin promoted osteoblast proliferation and differentiation through MAPK and PI3K pathway in MG-63 cells.
University of Science and Technology of China, Hefei, China.
Jianhong
J
Yang
Xiaolin
X
Zhang
Weiwei
W
Wang
Jing
J
Liu
D000469:Alkaline Phosphatase / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002867:Chromones / Q000494:pharmacology; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
D002867:Chromones; D050659:Core Binding Factor Alpha 1 Subunit; D005419:Flavonoids; D007004:Hypoglycemic Agents; D007328:Insulin; D009025:Morpholines; D047428:Protein Kinase Inhibitors; C493709:RUNX2 protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one