Open Access

All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts

  • Authors:
    • Ying Shao
    • Qian-Zhao Chen
    • Yu-Hua Zeng
    • Yang Li
    • Wen-Yan Ren
    • Lin-Yun Zhou
    • Rong-Xin Liu
    • Ke Wu
    • Jun-Qing Yang
    • Zhong-Liang Deng
    • Yu Yu
    • Wen-Juan Sun
    • Bai-Cheng He
  • View Affiliations

  • Published online on: October 19, 2016     https://doi.org/10.3892/ijmm.2016.2782
  • Pages: 1693-1702
  • Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Rosiglitazone (RSG) is a potent drug used in the treatment of insulin resistance; however, it is associated with marked skeletal toxicity. RSG-induced osteoporosis may contribute to the promotion of adipogenic differentiation at the expense of osteogenic differentiation in bone marrow stromal cells. The aim of this study was to investigate whether RSG-induced bone toxicity can be reversed by combined treatment with all-trans retinoic acid (ATRA). We examined different osteogenic markers in mouse embryonic fibroblasts (MEFs) following treatment with RSG, ATRA, or RSG and ATRA in combination. We examined the effects of RSG and/or ATRA on ectopic bone formation, and dissected the possible molecular mechanisms underlying this process. We found that ATRA or RSG both induced alkaline phosphatase (ALP) activity in the MEFs, and that the ATRA-induced ALP activity was enhanced by RSG and vice versa. However, only the combination of RSG and ATRA increased the expression of osteopontin and osteocalcin, promoted matrix mineralization, and induced ectopic ossification in MEFs. Mechanistically, we found that the osteogenic differentiation induced by the combination of RSG and ATRA may be mediated partly by suppressing RSG-induced adipogenic differentiation and activating bone morphogenetic protein (BMP)/Smad signaling. On the whole, our findings demonstrate that RSG in combination with ATRA promotes the commitment of MEFs to the osteoblast lineage. Thus, the combination of these two agents may prove to be a promising and novel therapeutic regimen for insulin resistance without skeletal toxicity. It may also be a better strategy with which to prevent RSG-induced osteoporosis.
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December-2016
Volume 38 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Shao Y, Chen Q, Zeng Y, Li Y, Ren W, Zhou L, Liu R, Wu K, Yang J, Deng Z, Deng Z, et al: All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts. Int J Mol Med 38: 1693-1702, 2016
APA
Shao, Y., Chen, Q., Zeng, Y., Li, Y., Ren, W., Zhou, L. ... He, B. (2016). All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts. International Journal of Molecular Medicine, 38, 1693-1702. https://doi.org/10.3892/ijmm.2016.2782
MLA
Shao, Y., Chen, Q., Zeng, Y., Li, Y., Ren, W., Zhou, L., Liu, R., Wu, K., Yang, J., Deng, Z., Yu, Y., Sun, W., He, B."All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts". International Journal of Molecular Medicine 38.6 (2016): 1693-1702.
Chicago
Shao, Y., Chen, Q., Zeng, Y., Li, Y., Ren, W., Zhou, L., Liu, R., Wu, K., Yang, J., Deng, Z., Yu, Y., Sun, W., He, B."All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts". International Journal of Molecular Medicine 38, no. 6 (2016): 1693-1702. https://doi.org/10.3892/ijmm.2016.2782