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β-mercaptoethanol promotes osteogenesis of human mesenchymal stem cells via sirt1-ERK pathway

Cytotechnology volume 72, pages 695–706 (2020)Cite this article

Abstract

Human umbilical cord-derived mesenchymal stem cells (hUMSCs) hold strong self-renewal capacity and low immunogenicity, which have attracted attention as potential candidates for bone repair and regeneration. However, insufficient osteogenic differentiation markedly hinders the clinical applications of hUMSCs. In the present study, the effect of β-mercaptoethanol (BME), a small molecule antioxidant which has been identified to regulate cell proliferation and differentiation, on osteogenic differentiation of hUMSCs and underlying signaling mechanism were investigated. The results indicated that under osteogenic induction conditions, BME treatment increased the alkaline phosphatase (ALP) activity and promoted calcium mineralization in hUMSCs. The gene and protein expression of osteogenesis-related markers such as ALP, osteopontin (OPN), osteocalcin (OCN) and collagen type I (COLI) were also significantly up-regulated. Besides, BME promoted the protein expression of silent information regulator type 1 (sirt1) and stimulated the activation of extracellular signal-related kinase (ERK), contributing to increased Runx2 expression. Furthermore, blocking the expression of sirt1 attenuated BME-enhanced ERK phosphorylation and osteogenic differentiation of hUMSCs. These results indicated that BME accelerated osteogenic differentiation of hUMSCs by activating the sirt1-ERK signaling pathway, thereby providing insights into the development of MSCs-based bone regeneration strategies.

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All data generated during this study are included in this published article.

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Abbreviations

hUMSCs:

Human umbilical cord-derived mesenchymal stem cells

BME:

β-mercaptoethanol

ALP:

Alkaline phosphatase

OPN:

Osteopontin

OCN:

Osteocalcin

COLI:

Collagen type I

sirt1:

Silent information regulator type 1

ERK:

Extracellular signal-related kinase

ROS:

Reactive oxygen species

CCK-8:

Cell counting kit-8

OIM:

Osteogenic induction medium

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Funding

This research was supported by the National Key Research and Development Program of China (Grant No. 2018YFC1105800), the National Natural Science Foundation of China (Grant No. 81671841), the Fundamental Research Funds for the Central Universities (Grant No. 22221818014).

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Affiliations

  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei-Long Road, P. O. Box 309#, Shanghai, 200237, People’s Republic of China

    Jiaxing Liu, Hui Wang, Wenxia Ren, Yan Zhou, Zhaoyang Ye & Wen-Song Tan

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  1. Jiaxing Liu
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  2. Hui Wang
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  3. Wenxia Ren
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  4. Yan Zhou
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  5. Zhaoyang Ye
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  6. Wen-Song Tan
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Correspondence to Yan Zhou.

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Liu, J., Wang, H., Ren, W. et al. β-mercaptoethanol promotes osteogenesis of human mesenchymal stem cells via sirt1-ERK pathway. Cytotechnology 72, 695–706 (2020). https://doi.org/10.1007/s10616-020-00412-9

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  • DOI: https://doi.org/10.1007/s10616-020-00412-9

Keywords

  • Umbilical cord-derived mesenchymal stem cells
  • Osteogenic differentiation
  • β-mercaptoethanol
  • sirt1
  • ERK