Lanthanum enhances in vitro osteoblast differentiation via pertussis toxin-sensitive gi protein and ERK signaling pathway.
Converging lines of evidence suggest that lanthanum tends to deposit in bone. The influence of lanthanum ion (La3+) on osteoblast differentiation and the related mechanism are essential to understanding its effect on bone metabolism. In this study, La3+ treatment enhanced in vitro osteoblast differentiation as evidenced by promoting alkaline phosphatase (ALP) activity, osteocalcin (OC) secretion, and matrix mineralization. The expressions of osteoblast-specific genes of Cbfa-1, osteopontin (OPN), and bone sialoprotein (BSP) were all increased in the presence of La3+, but no change was observed in that of type I collagen (COL-I). Further studies demonstrated that La3+ treatment enhanced phosphorylation of extracellular signal-regulated kinase (ERK). Inhibition of ERK activation by U0126 suppressed the effects of La3+ on osteoblast activity. Moreover, pretreatment of the cells with pertussis toxin (PTx), a Gi protein inhibitor, suppressed the La3+-enhanced ERK phosphorylation and osteoblast differentiation. These findings suggest that La3+ exposure enhances in vitro osteoblast differentiation and the effect depends on ERK phosphorylation via PTx-sensitive Gi protein signaling.
Wang
Xi
X
Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, 38 Xueyuan Road, Beijing 100191, PR China.
Yuan
Lan
L
Huang
Jian
J
Zhang
Tian-Lan
TL
Wang
Kui
K
D000818:Animals; D002454:Cell Differentiation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D007811:Lanthanum / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007811:Lanthanum; D037342:Pertussis Toxin; D048049:Extracellular Signal-Regulated MAP Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go