Ovotransferrin, a major protein in egg white, induces osteoblast proliferation and survival in vitro. However, it is unclear which receptor(s) drive the beneficial activities of this bioactive glycoprotein. We examined the role of the low-density lipoprotein receptor-related protein 1 (LRP1) in the actions of ovotransferrin on osteoblasts. Here, we showed that LRP1 in part regulates osteogenic action of ovotransferrin. Mouse osteoblasts, MC3T3-E1, with LRP1 deletion displayed diminished osteogenic activity. Our findings indicate that the bone-stimulatory impact of ovotransferrin on RUNX2, COL1A2, and Ca2+ signaling is LRP1-dependent. This shows that LRP1 not only acts as a scavenger receptor but also participates in ovotransferrin-mediated gene transcription. However, some of the key bone formatting factors such as ALP synthesis and serine residue phosphorylation of Akt by ovotransferrin remained independent of LRP1. Overall, this study shows that LRP1–ovotransferrin interaction might underline in part the ability of ovotransferrin to promote bone formation.
