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Open AccessArticle

25-Hydroxycholesterol Inhibits Adipogenic Differentiation of C3H10T1/2 Pluripotent Stromal Cells

1
Department of Animal Science, University of Manitoba, 201 Animal Science building, Winnipeg, MB R3T 2N2, Canada
2
Department of Poultry Science, University of Georgia, 303 Poultry Science building, Athens, GA 30602-2772, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 412; https://doi.org/10.3390/ijms21020412
Received: 10 September 2019 / Revised: 30 December 2019 / Accepted: 2 January 2020 / Published: 9 January 2020
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2020)
Understanding of adipogenesis is important to find remedies for obesity and related disorders. In addition, it is also critical in bone disorders because there is a reciprocal relationship between adipogenesis and osteogenesis in bone micro-environment. Oxysterols are pro-osteogenic and anti-adipogenic molecules via hedgehog activation in pluripotent bone marrow stomal cells. However, no study has evaluated the role of specific oxysterols in C3H10T1/2 cells, which are a good cell model for studying osteogenesis and adipogenesis in bone-marrows. Thus, we investigated the effects of specific oxysterols on adipogenesis and expression of adipogenic transcripts in C3H10T1/2 cells. Treatment of cells with DMITro significantly induced mRNA expression of Pparγ. This induction was significantly inhibited by 25-HC. The expression of C/cepα, Fabp4 and Lpl was also inhibited by 25-HC. To determine the mechanism by which 25-HC inhibits adipogenesis, the effects of the hedgehog signalling pathway inhibitor, cyclopamine and CUR61414, were evaluated. Treatment of C3H10T1/2 cells with DMITro + cyclopamine or DMITro + CUR61414 for 96h did not modulate adipocyte differentiation; cyclopamine and CUR61414 did not reverse the inhibitory effects of 25-HC, suggesting that the canonical hedgehog signalling may not play a role in the anti-adipogenic effects of 25-HC in C3H10T1/2 cells. In addition, LXR agonist did not inhibit adipogenesis, but 25-HC strongly inhibits adipogenesis of C3H10T1/2 cells. Our observations showed that 25-HC was the most potent oxysterol in inhibiting adipogenesis and the expression of key adipogenic transcripts in C3H10T1/2 cells among the tested oxysterols, suggesting its potential application in providing an intervention in osteoporosis and obesity. We also report that the inhibitory effects of 25-HC on adipogenic differentiation in C3H10T1/2 cells are not mediated by hedgehog signaling and LXR. View Full-Text
Keywords: oxysterols; C3H10T1/2 stromal cells; differentiation; hedgehog signalling; PPARγ; ADD1/SREBF1 oxysterols; C3H10T1/2 stromal cells; differentiation; hedgehog signalling; PPARγ; ADD1/SREBF1
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MDPI and ACS Style

Moseti, D.; Regassa, A.; Chen, C.; O, K.; Kim, W.K. 25-Hydroxycholesterol Inhibits Adipogenic Differentiation of C3H10T1/2 Pluripotent Stromal Cells. Int. J. Mol. Sci. 2020, 21, 412. https://doi.org/10.3390/ijms21020412

AMA Style

Moseti D, Regassa A, Chen C, O K, Kim WK. 25-Hydroxycholesterol Inhibits Adipogenic Differentiation of C3H10T1/2 Pluripotent Stromal Cells. International Journal of Molecular Sciences. 2020; 21(2):412. https://doi.org/10.3390/ijms21020412

Chicago/Turabian Style

Moseti, Dorothy; Regassa, Alemu; Chen, Chongxiao; O, Karmin; Kim, Woo K. 2020. "25-Hydroxycholesterol Inhibits Adipogenic Differentiation of C3H10T1/2 Pluripotent Stromal Cells" Int. J. Mol. Sci. 21, no. 2: 412. https://doi.org/10.3390/ijms21020412

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