title: PPARγ and Wnt Signaling in Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells.
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.
authors.forename: Zongyi
authors.initials: Z
authors.lastname: Yuan
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Shihong
authors.initials: S
authors.lastname: Luo
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.forename: Daowen
authors.initials: D
authors.lastname: Luo
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Dongdong
authors.initials: D
authors.lastname: Zhang
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Rao
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Luzhou Medical College, No.2, Jiang Yang Nan Road, Luzhou 646000, P.R.China. drxiaojg@sohu.com.
authors.forename: Jingang
authors.initials: J
authors.lastname: Xiao
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005786:Gene Expression Regulation; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D035683:MicroRNAs / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D047495:PPAR gamma / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D035683:MicroRNAs; D047495:PPAR gamma; C493709:RUNX2 protein, human; D051153:Wnt Proteins; D051176:beta Catenin; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase