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Sphingosine-1-phosphate inhibits differentiation of C3H10T1/2 cells into adipocyte

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Abstract

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.

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Abbreviations

ALP:

Alkaline phosphatase

cAMP:

Cyclic AMP

C/EBP:

CAAT/enhancer-binding protein

DEX:

Dexamethasone

FABP4:

Fatty acid-binding protein 4

GPCR:

G-protein-coupled receptor

IBMX:

Isobutylmethylxanthine

OC:

Osteocalcin

PI3K:

Phosphatidylinositol 3-kinase

PKA:

Protein kinase A

PPARγ:

Peroxisome proliferator-activated receptor γ

SPHK:

Sphingosine kinase

S1P:

Sphingosine-1-phosphate

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Acknowledgments

This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants-in-Aid for Scientific Research: 26462886 to EM, 24229009 to MH, 25253201 to FN). We would like to thank the Research Support Center, Graduate School of Medical Sciences, Kyushu University for assistance.

Conflict of interest

The authors state that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Periodontal Section, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

    Yoko Hashimoto, Etsuko Matsuzaki, Katsumasa Higashi, Aiko Takano & Fusanori Nishimura

  2. Department of Operative Dentistry and Endodontology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-Ku, Fukuoka, 814-0193, Japan

    Etsuko Matsuzaki

  3. Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Fumi Takahashi-Yanaga

  4. Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

    Masato Hirata

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  1. Yoko Hashimoto
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Correspondence to Etsuko Matsuzaki.

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Hashimoto, Y., Matsuzaki, E., Higashi, K. et al. Sphingosine-1-phosphate inhibits differentiation of C3H10T1/2 cells into adipocyte. Mol Cell Biochem 401, 39–47 (2015). https://doi.org/10.1007/s11010-014-2290-1

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  • DOI: https://doi.org/10.1007/s11010-014-2290-1

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