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01-01-2013 | Original article

Retinoic acid regulates commitment of undifferentiated mesenchymal stem cells into osteoblasts and adipocytes

Authors: Kunihiro Hisada, Kenji Hata, Fumitaka Ichida, Takuma Matsubara, Hideo Orimo, Tamaki Nakano, Hirohumi Yatani, Riko Nishimura, Toshiyuki Yoneda

Published in: Journal of Bone and Mineral Metabolism | Issue 1/2013

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.

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Title: Retinoic acid regulates commitment of undifferentiated mesenchymal stem cells into osteoblasts and adipocytes
Authors: Kunihiro Hisada
Kenji Hata
Fumitaka Ichida
Takuma Matsubara
Hideo Orimo
Tamaki Nakano
Hirohumi Yatani
Riko Nishimura
Toshiyuki Yoneda
Publication date: 01-01-2013
Publisher: Springer Japan
Published in: Journal of Bone and Mineral Metabolism / Issue 1/2013
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-012-0385-x

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