J Appl Biomed 19:159-169, 2021 | DOI: 10.32725/jab.2021.016

A-769662 stimulates the differentiation of bone marrow-derived mesenchymal stem cells into osteoblasts via AMP-activated protein kinase-dependent mechanism

Basem M. Abdallah*, Abdullah M. Alzahrani
King Faisal University, College of Science, Biological Sciences Department, Al-Ahsa, Saudi Arabia

AMP-activated protein kinase (AMPK) signaling shows an important role in energy metabolism and has recently been involved in osteogenic and adipogenic differentiation. In this study we aimed to investigate the role of AMPK activator, A-769662, in regulating the differentiation of mesenchymal stem cells derived from bone marrow (BMSCs) into osteoblastic and adipocytic cell lineage. The effect of A-769662 on osteogenesis was assessed by quantitative alkaline phosphatase (ALP) activity, matrix mineralization stained with Alizarin red, and gene expression analysis by quantitative polymerase chain reaction (qPCR). Adipogenesis was determined by Oil Red O staining for fat droplets and qPCR analysis of adipogenic markers. A-769662 activated the phosphorylation of AMPKα1 during the osteogenesis of mBMSCs as revealed by western blot analysis. A-769662 promoted the early stage of the commitment of mouse (m) BMSCs differentiation into osteoblasts, while inhibiting their differentiation into adipocytes in a dose-dependent manner. The effects of A-769662 on stimulating osteogenesis and inhibiting adipogenesis of mBMSCs were significantly eliminated in the presence of either AMPKα1 siRNA or Compound C, an inhibitor of AMPK pathway. In conclusion, we identified A-769662 as a new compound that promotes the commitment of BMSCs into osteoblasts versus adipocytes via AMPK-dependent mechanism. Thus our data show A-769662 as a potential osteo-anabolic drug for treatment of osteoporosis.

Keywords: A-769662; Adipocyte; AMPK; BMSC; Osteoblast; Stem cells
Grants and funding:

This work was funded by the Deanship of Scientific Research at King Faisal University, Saudi Arabia (Grant No. 180076).

Conflicts of interest:

The authors declare that they have no competing interests.

Received: December 30, 2020; Revised: June 18, 2021; Accepted: June 21, 2021; Prepublished online: July 1, 2021; Published: September 17, 2021  Show citation

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Abdallah BM, Alzahrani AM. A-769662 stimulates the differentiation of bone marrow-derived mesenchymal stem cells into osteoblasts via AMP-activated protein kinase-dependent mechanism. J Appl Biomed. 2021;19(3):159-169. doi: 10.32725/jab.2021.016. PubMed PMID: 34907759.
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