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  3. PI3K-Akt signaling regulates BMP2-induced osteogenic differentiation of mesenchymal stem cells (MSCs): A transcriptomic landscape analysis

PI3K-Akt signaling regulates BMP2-induced osteogenic differentiation of mesenchymal stem cells (MSCs): A transcriptomic landscape analysis

  • Stem Cell Res. 2022 Dec 23;66:103010. doi: 10.1016/j.scr.2022.103010.
Shengqiang Gao 1,  Bowen Chen 1,  Zhenglin Zhu 1,  Chengcheng Du 1,  Jing Zou 1,  Yaji Yang 1,  Wei Huang 2,  Junyi Liao 3
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Research Laboratory, Chongqing Medical University, Chongqing 400016, China.
  • 2 Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Research Laboratory, Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected].
  • 3 Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Research Laboratory, Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected].
PMID: 36580886 DOI: 10.1016/j.scr.2022.103010
Abstract

Bone Morphogenetic Protein 2 (BMP2) effectively induced mesenchymal stem cells (MSCs) osteogenic differentiation hold great potential for bone tissue engineering. However, a global mechanistic view of BMP2-induced osteogenic differentiation of MSCs remains to be fully elucidated. Here, human umbilical cord-derived MSCs (UC-MSCs) were induced with BMP2, three days and five days later, total RNA were extracted and subjected to RNA-sequencing (RNA-Seq) followed with bioinformatic analysis. Osteogenic differentiation abilities were evaluated with Alkaline Phosphatase (ALP) staining and osteogenic differentiation marker expression at both mRNA and protein levels. We identified that adenoviral vectors effectively transduced in UC-MSCs and expressed BMP2 in high efficiency. Both on day 3 and day 5, differentially expressed genes (DEGs) were highly enriched in PI3K-Akt signaling pathway. As for the common DEGs among total BMP2 group vs control group, BMP2 (day 3) versus control (day 3) and BMP2 (day 5) versus control (day 5), there were 105 DGEs and highly enriched in PI3K-Akt signaling pathway. Finally, we found that PI3K-Akt signaling inhibitor dramatically inhibited BMP2-iduced osteogenic differentiation of UC-MSCs. We firstly identified that PI3K-Akt signaling pathway plays a pivotal role in BMP2-induced osteogenic differentiation of MSCs, which may apply a new perspective for BMP2 based bone tissue engineering.

Keywords

BMP2; Bone tissue engineering; Mesenchymal stem cells; Osteogenic differentiation; PI3K-Akt signaling.

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