GSK3 inhibitor AR-A014418 promotes osteogenic differentiation of human adipose-derived stem cells via ERK and mTORC2/Akt signaling pathway.

Min Zhang, Ping Zhang, Yunsong Liu, Yongsheng Zhou

Biochemical and biophysical research communications 2017 Aug 19

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Small molecule-based bone tissue engineering is emerging as a promising strategy for bone defects restoration. In this study, we intended to identify the roles and mechanisms of AR-A014418, a highly selective inhibitor of GSK3, on the osteogenic differentiation. We found that AR-A014418 exhibited a dose-dependent effect on osteogenic differentiation of human adipose-derived stem cells (hASCs). hASCs treated with AR-A014418 showed higher activity of ERK and mTORC2/Akt signaling. Administration of ERK inhibitor U0126 or knockdown of RICTOR by siRNA attenuated AR-A014418 induced osteogenic differentiation of hASCs. Our results suggested that AR-A014418 significantly promoted osteogenic potential of hASCs partially by the activation of ERK and mTORC2/Akt signaling pathway, and might be used for bone tissue engineering as an osteo-inductive factor. Copyright © 2017 Elsevier Inc. All rights reserved.

Citation

Min Zhang, Ping Zhang, Yunsong Liu, Yongsheng Zhou. GSK3 inhibitor AR-A014418 promotes osteogenic differentiation of human adipose-derived stem cells via ERK and mTORC2/Akt signaling pathway. Biochemical and biophysical research communications. 2017 Aug 19;490(2):182-188