Eicosapentaenoic acid-containing phosphatidylcholine promotes osteogenesis:mechanism of up-regulating Runx2 and ERK-mediated phosphorylation of PPARγ at serine 112

Abstract

In this study, the pro-osteogenic effects of EPA-containing phosphatidylcholine (EPA-PC), a natural agonist of peroxisome proliferator-activated receptor (PPARγ), were first investigated both in vitro and in vivo. In vitro experiments showed that EPA-PC promoted mesenchymal stem cells (MSCs) differentiation into osteoblasts over adipocytes, which was contrary to the role of rosiglitazone, a well-known full PPARγ agonist. qRT-PCR and western blotting indicated that EPA-PC significantly increased the mRNA and protein levels of osteogenesis-related genes, such as Runx2, ALP and COL-I. Although EPA-PC promoted mRNA expression of PPARγ, it didn’t affect the protein level of PPARγ. Furthermore, EPA-PC promoted ERK-mediated phosphorylation of PPARγ at serine 112, which was positively associated with osteogenesis. In vivo experiments indicated that EPA-PC increased bone formation rate and enhanced bone biomechanical properties of adolescent mice. In summary, our study showed that EPA-PC promoted osteogenesis by up-regulating Runx2 expression and ERK-regulated serine 112 phosphorylation of PPARγ, which enhanced our understanding about the action mode of PPARγ agonists.