caa a22 4500 606236996 CHVBK 20210128101250.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s11010-014-2290-1 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2290-1 Sphingosine-1-phosphate inhibits differentiation of C3H10T1/2 cells into adipocyte [Elektronische Daten] [Yoko Hashimoto, Etsuko Matsuzaki, Katsumasa Higashi, Fumi Takahashi-Yanaga, Aiko Takano, Masato Hirata, Fusanori Nishimura] Mesenchymal stem cells (MSCs) can differentiate into a number of cell types, including adipocytes and osteoblasts. MSC differentiation into adipocytes inhibits osteogenic differentiation and vice versa. Therefore, understanding the mechanisms of MSC differentiation at the signaling level can lead to the development of novel therapeutic strategies toward tissue regeneration. Sphingosine-1-phosphate (S1P) is a signaling molecule that regulates many cellular responses, including cellular differentiation. However, the effects of S1P on MSC differentiation are largely unknown. The purpose of study was to investigate whether S1P drives MSCs toward either adipogenic or osteogenic differentiation, and if so, to clarify the underlying signaling mechanisms for such differentiation. We found that S1P inhibited adipogenic differentiation of C3H10T1/2 multipotent stem cells, while promoting their osteogenic differentiation. During adipogenic differentiation, S1P suppressed the cAMP accumulation in a Gi-protein-dependent manner. The Gi-dependent S1P signaling suppressed C/EBPβ expression, which is essential for adipogenic differentiation. Furthermore, S1P did not affect cAMP-independent adipogenic differentiation. These findings suggest that S1P suppresses cAMP accumulation, leading to inhibition of C/EBPβ expression, thereby resulting in decreased adipogenic differentiation of C3H10T1/2 cells. Thus, our findings provide novel molecular mechanisms as regards how S1P inhibits adipogenic differentiation of C3H10T1/2 cells, indicating a potential beneficial role for regeneration and repair of tissues. Springer Science+Business Media New York, 2014 cAMP nationallicence C/EBPβ nationallicence Adipogenic differentiation nationallicence Mesenchymal stem cell nationallicence C3H10T1/2 nationallicence Sphingosine-1-phosphate nationallicence ALP : Alkaline phosphatase nationallicence cAMP : Cyclic AMP nationallicence C/EBP : CAAT/enhancer-binding protein nationallicence DEX : Dexamethasone nationallicence FABP4 : Fatty acid-binding protein 4 nationallicence GPCR : G-protein-coupled receptor nationallicence IBMX : Isobutylmethylxanthine nationallicence OC : Osteocalcin nationallicence PI3K : Phosphatidylinositol 3-kinase nationallicence PKA : Protein kinase A nationallicence PPARγ : Peroxisome proliferator-activated receptor γ nationallicence SPHK : Sphingosine kinase nationallicence S1P : Sphingosine-1-phosphate nationallicence Hashimoto Yoko Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut Matsuzaki Etsuko Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut Higashi Katsumasa Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut Takahashi-Yanaga Fumi Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan aut Takano Aiko Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut Hirata Masato Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut Nishimura Fusanori Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 401/1-2(2015-03-01), 39-47 0300-8177 401:1-2<39 2015 401 11010 https://doi.org/10.1007/s11010-014-2290-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2290-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hashimoto Yoko Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 700 1- Matsuzaki Etsuko Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 700 1- Higashi Katsumasa Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 700 1- Takahashi-Yanaga Fumi Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 700 1- Takano Aiko Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 700 1- Hirata Masato Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 700 1- Nishimura Fusanori Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 401/1-2(2015-03-01), 39-47 0300-8177 401:1-2<39 2015 401 11010