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 (La(3+)) on osteoblast differentiation and the related mechanism are essential to understanding its effect on bone metabolism. In this study, La(3+) 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 La(3+), but no change was observed in that of type I collagen (COL-I). Further studies demonstrated that La(3+) treatment enhanced phosphorylation of extracellular signal-regulated kinase (ERK). Inhibition of ERK activation by U0126 suppressed the effects of La(3+) on osteoblast activity. Moreover, pretreatment of the cells with pertussis toxin (PTx), a Gi protein inhibitor, suppressed the La(3+)-enhanced ERK phosphorylation and osteoblast differentiation. These findings suggest that La(3+) exposure enhances in vitro osteoblast differentiation and the effect depends on ERK phosphorylation via PTx-sensitive Gi protein signaling. J. Cell. Biochem. 105: 1307-1315, 2008. (c) 2008 Wiley-Liss, Inc.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000261539100018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemistry & Molecular BiologyCell BiologySCI(E)PubMed25ARTICLE51307-131510