TGF‐β/BMP signaling pathway is involved in cerium‐promoted osteogenic differentiation of mesenchymal stem cells

Abstract

The extensive applications of cerium (Ce) increased the chance of human exposure to Ce and its compounds. It was reported that Ce was mainly deposited in the bone after administration. However, the potential effect and mechanism of Ce on bone metabolism are not well understood. In this study, we investigated the cellular effects of Ce on the differentiation of mesenchymal stem cells (MSCs) and the associated molecular mechanisms. The results indicated that Ce promoted the osteogenic differentiation and inhibited the adipogenic differentiation of MSCs at cell level. Genes involved in transforming growth factor-β/bone morphogenetic proteins (TGF-β/BMP) signaling pathway were significantly changed when the MSCs were exposed to 0.0001 µM Ce by RT(2) Profiler™ PCR Array analysis. The expression of genes and proteins related to pathways, osteogenic, and adipogenic biomarkers of MSCs upon interaction with Ce was further confirmed by quantitative real-time reverse transcriptase polymerase chain reaction (Q-PCR) and Western blot analysis. The results suggest that Ce exerts the effects by interacting with bone morphogenetic protein receptor (BMPR) and activates TGF-β/BMP signaling pathway, leads to the up-regulation of the osteogenic master transcription factor, runt-related transcription factor 2 (Runx 2), and the down-regulation of the adipocytic master transcription factor, peroxisome proliferator-activated receptor gamma 2 (PPARγ2). Runx2, which subsequently up-regulates osteoblast (OB) marker genes collagen I (Col I) and BMP2 at early stages, alkaline phosphatase (ALP), and osteocalcin (OCN) at later stages of differentiation, thus driving MSCs to differentiate into OBs. The results provide novel evidence to elucidate the mechanisms of bone metabolism by Ce.

Comparison of the Transcriptomes of Mouse Skin Derived Precursors (SKPs) and SKP-Derived Fibroblasts (SFBs) by RNA-Seq

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A Positive Role of MicroRNA‐15b on Regulation of Osteoblast Differentiation

“…The existence of an osteoblast is committed through the cascade of osteoprogenitors and pre-osteoblasts; each step is tightly regulated by various types of growth factors, cytokines, signaling molecules, hormones, morphogens etc (Chen et al, 2012; Liu et al, 2013; Raggatt et al, 2008; Monroe et al, 2012; Selvamurugan et al, 2000). Any kind of modification or deficiency in these regulators may lead to pathological effects.…”

Mineral trioxide aggregate induces osteoblastogenesis via Atf6

“…As BMP signal through the expression of Runx2 enhances Bglap gene expression (Guo et al, 2012, Liu et al, 2013) and the Bglap gene was also driven by Atf6 (Jang et al, 2012), we examined Bmp-2, Bmp-4, and Atf6 expression in the presence or absence of MTA. MTA treatment affected neither BMP-2 nor BMP-4 expression (Fig.…”