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. 2017 Aug 19;490(2):182-188.
doi: 10.1016/j.bbrc.2017.06.018. Epub 2017 Jun 8.

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

Min Zhang  1 , Ping Zhang  2 , Yunsong Liu  3 , Yongsheng Zhou  4
Affiliations

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

Min Zhang et al. Biochem Biophys Res Commun. .

Abstract

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.

Keywords: AR-A014418; ERK1/2; GSK3; Human adipose-derived stem cells (hASCs); Osteogenic differentiation; RICTOR.

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