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Effect of GSK-137647A, the First Non-Carboxylic FFA4 Agonist, on the Osteogenic and Adipogenic Differentiation of Bone Mesenchymal Stem Cells in db/db Mice

Chunlei Wang, Yanmei Liu, Yuan Pan, Hui Jin

J Pharm Pharmacol. 2020 Mar;72(3):461-469.

PMID: 31858612

Abstract:

Objective:
To investigate the effect of GSK-137647A, the first non-carboxylic FFA4 agonist, on osteogenic and adipogenic differentiation of bone mesenchymal stem cells (BMSCs) of db/db mice.
Methods:
Bone mesenchymal stem cells were extracted from 8-week-old db/db mice. Cell Counting Kit-8 was used to evaluate the toxicity of GSK-137647A on BMSCs, and the optimal concentration of GSK-137647A was selected to investigate the osteogenic and adipogenic differentiation of BMSCs, and relevant indicators of osteoblasts and adipocytes were detected.
Key findings:
GSK-137647A had no significant toxicity on cell growth and proliferation. Moreover, GSK-137647A showed a significant increase in mineralization of BMSCs differentiated osteoblasts compared to the control group and elevated the alkaline phosphatase (ALP) activity in a time-dependent manner. Meanwhile, the treatment of GSK-137647A decreased the adipogenic differentiation of BMSCs. The expression levels of ALP, runt-related transcription factor 2, bone morphogenetic protein 4, osterix and β-catenin were significantly increased in GSK-137647A-treated group, while the gene and protein levels of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α were significantly reduced.
Conclusions:
All of these results demonstrated that GSK-137647A suppressed the adipogenic differentiation and promoted osteogenic differentiation of BMSCs, which is partly attributed to the increased expression of β-catenin in wingless/integrated signalling pathway.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP349085821 GSK137647A GSK137647A 349085-82-1 Price
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