Open AccessEffect of GSK‐137647A, the first non‐carboxylic FFA4 agonist, on the osteogenic and adipogenic differentiation of bone mesenchymal stem cells in db/db mice
Author(s) -
Wang Chunlei,
Liu Yanmei,
Pan Yuan,
Jin Hui
Publication year - 2020
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13217
Subject(s) - adipogenesis , alkaline phosphatase , runx2 , mesenchymal stem cell , chemistry , cellular differentiation , bone morphogenetic protein 2 , endocrinology , stem cell , microbiology and biotechnology , wnt signaling pathway , medicine , signal transduction , biology , biochemistry , in vitro , gene , enzyme
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.