title: Inhibiting PPARγ by erythropoietin while upregulating TAZ by IGF1 synergistically promote osteogenic differentiation of mesenchymal stem cells.
abstract: Erythropoietin (EPO) is reported to promote osteogenesis and inhibit adipogenesis of mesenchymal stem cells (MSC) through inhibiting PPARγ, while insulin-like growth factor 1 (IGF1) is able to enhance osteogenesis via upregulating transcriptional coactivator with PDZ-binding motif (TAZ). The different targets of EPO and IGF1 suggested their potential synergism to enhance osteogenesis. In this study, we aimed to determine the potential synergism of EPO and IGF1 and its efficacy on MSC differentiation. Rat adipose-derived mesenchymal stem cells (ADSCs) were separately treated with EPO, IGF1 and EPO/IGF1. It was observed that the co-treatment using EPO and IGF1 was able to potently promote the osteogenic differentiation of rat ADSCs compared with EPO or IGF1 alone, which offered a promising effective option to strengthen bone tissue regeneration for bone defects. Further, we demonstrated that the enhanced osteogenic differentiation by EPO and IGF1 co-treatment was almost counteracted by activating PPARγ through PPARγ agonist, RSG, and blocking TAZ through TAZ silencing RNA, siTAZ. Thus, it could be concluded that EPO and IGF1 possessed a potent synergism in promoting osteogenic differentiation, and the synergism was mainly attributed to co-regulation of different osteogenic regulators PPARγ and TAZ, which were targeted genes of EPO and IGF1 respectively.
authors.affiliation: Department of Orthopedics, Beijing Tongren Hospital, Capital Medical University, No.1, Dongjiaominxiang, Dongcheng District, Beijing, 100730, People's Republic of China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Beijing Tongren Hospital, Capital Medical University, No.1, Dongjiaominxiang, Dongcheng District, Beijing, 100730, People's Republic of China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Orthopedics, Beijing Tongren Hospital, Capital Medical University, No.1, Dongjiaominxiang, Dongcheng District, Beijing, 100730, People's Republic of China. Electronic address: mayuquan2016@sina.com.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C583557:IGF1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D047495:PPAR gamma; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D004921:Erythropoietin; D007334:Insulin-Like Growth Factor I
keywords: Erythropoietin; Insulin-like growth factor 1; Osteogenic differentiation; Rat adipose-derived mesenchymal stem cells