RRC ID 44073
著者 Hisada K, Hata K, Ichida F, Matsubara T, Orimo H, Nakano T, Yatani H, Nishimura R, Yoneda T.
タイトル Retinoic acid regulates commitment of undifferentiated mesenchymal stem cells into osteoblasts and adipocytes.
ジャーナル J Bone Miner Metab
Abstract Evidence indicates that the balance between osteoblastogenesis and adipogenesis of mesenchymal stem cells (MSCs) is regulated by several hormones, growth factors, and their downstream signaling cascades. Previous studies suggest that retinoic acid (RA) plays a role in osteoblastogenesis and adipogenesis. However, it is unknown whether RA regulates commitment of MSCs into osteoblasts and adipocytes. In this study, we investigated the role of RA in differentiation of MSCs using the C3H10T1/2 cell line. RA stimulated activity and expression of alkaline phosphatase (ALP) and upregulated activity of the ALP gene promoter. The effects of RA were further enhanced by bone morphogenetic protein 2 (BMP2) and resultant Smad signaling. Furthermore, overexpression of Runx2 and Msx2, critical transcription factors for bone formation and BMP2-dependent osteoblastogenesis, enhanced RA-dependent ALP activity. In view of these findings, RA likely stimulates osteoblast differentiation through the BMP2-Smad-Runx2/Msx2 pathway. In contrast, RA markedly inhibited BMP2-induced adipocyte differentiation, suppressing expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein (C/EBP)α and C/EBPδ, and inhibiting adipogenic function of C/EBPβ, C/EBPδ, and PPARγ. In conclusion, our data suggest that RA regulates commitment of MSCs into osteoblasts and adipocytes by controlling transcriptional regulators.
巻・号 31(1)
ページ 53-63
公開日 2013-1-1
DOI 10.1007/s00774-012-0385-x
PMID 23014973
MeSH Adipocytes / cytology Adipocytes / metabolism* Alkaline Phosphatase / biosynthesis Animals Antineoplastic Agents / pharmacology* Bone Morphogenetic Protein 2 / biosynthesis CCAAT-Enhancer-Binding Protein-delta / metabolism CCAAT-Enhancer-Binding Proteins / metabolism Cell Differentiation / drug effects* Core Binding Factor Alpha 1 Subunit / biosynthesis Gene Expression Regulation / drug effects HEK293 Cells Homeodomain Proteins / biosynthesis Humans Mesenchymal Stem Cells / cytology Mesenchymal Stem Cells / metabolism* Mice Osteoblasts / cytology Osteoblasts / metabolism* PPAR gamma / metabolism Smad Proteins / metabolism Transcription, Genetic / drug effects Tretinoin / pharmacology*
IF 2.297
引用数 35
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL ENDOCRINOLOGY & METABOLISM
リソース情報
ヒト・動物細胞 293(RCB1637) 10T1/2(RCB0247) C2C12(RCB0987)