Title:PPARγ and Wnt Signaling in Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells
Volume: 11
Issue: 3
Author(s): Zongyi Yuan, Qing Li, Shihong Luo, Zhi Liu, Daowen Luo, Bo Zhang, Dongdong Zhang, Pengcheng Rao and Jingang Xiao
Affiliation:
Keywords:
Adipocyte differentiation, mesenchymal stem cells, microRNA, osteoblast differentiation, peroxisome proliferatoractivated
receptor γ, regenerative therapy, Wnt signaling.
Abstract: Mesenchymal stem cells (MSCs) arise from a variety of tissues, including bone marrow and
adipose tissue and, accordingly, have the potential to differentiate into multiple cell types, including
osteoblasts and adipocytes. Research on MSCs to date has demonstrated that a large number of transcription
factors and ectocytic or intrastitial signaling pathways regulate adipogenic and osteogenic
differentiation. A theoretical inverse relationship exists in adipogenic and osteogenic lineage commitment
and differentiation, such that signaling pathways induce adipogenesis at the expense of osteogenesis
and vice versa. For example, peroxisome proliferator-activated receptor γ(PPARγ), which belongs to the nuclear
hormone receptor superfamily of ligand-activated transcription factors, is known to function as a master transcriptional
regulator of adipocyte differentiation, and inhibit osteoblast differentiation. Moreover, recent studies have demonstrated
that inducers of osteogenic differentiation, such as bone morphogenetic protein (BMP) and Wnt, inhibit the function
of PPARγ transactivation during MSC differentiation towards adipocytes through a variety of mechanisms. To illustrate
this, the canonical Wnt/β-catenin pathway represses expression of PPARγ mRNA, whereas the noncanonical Wnt
pathway activates histone methyltransferases that inhibit PPARγ transactivation via histone H3 lysine 9 (H3K9) methylation
of its target genes. The role of microRNAs (miRNAs) in adipogenesis and osteoblastogenesis is garnering increased
attention, and studies in this area have shed light on the integration of miRNAs with Wnt signaling and transcription factors
such as Runx2 and PPARγ. This review summarizes our current understanding of the mechanistic basis of these signaling
pathways, and indicates future clinical applications for stem cell-based cell transplantation and regenerative therapy.