Reduced prostaglandin I 2 signaling in Arid5b −/− primary skeletal muscle cells attenuates myogenesis

The AT‐rich interaction domain (ARID) family of proteins regulates gene expression, development, and differentiation. Although Arid5b has important functions in adipogenesis and chondrogenesis, theroleofArid5b in skeletal muscle myogenesis has not been investigated. Therefore, we isolated primary skeletal muscle cells from Arid5b +/+ and Arid5b −/− mice and characterized differentiation in these cells. We found that Arid5b −/− primary skeletal muscle cells showed differentiation defects and impaired sarcomeric assembly. Microarray analysis revealed down‐regulation of the prostanoid biosynthesis pathway in Arid5b −/− myoblasts, including the genes encoding cyclo‐oxygenase (COX)‐1 ( Ptgsl ) and prostaglandin (PG)I synthase ( Ptgis ). Down‐regulation of COX‐1 and PGI synthase was confirmed by real‐time PCR and Western blot analyses. Correspondingly, the production of PGI 2 , as measured by ELISA, was reduced in Arid5b −/− cells relative to Arid5b +/+ cells. Boyden chamber assays showed that migration was increased but chemotaxis was impaired in Arid5b −/− cells. Myoblast fusion was also inhibited in Arid5b −/− cells compared with Arid5b +/+ cells. Treatment with the PGI 2 analog iloprost rescued the defects in myotube formation, migration, and fusion. These results demonstrate that Arid5b has a novel and essential role in skeletal muscle differentiation by regulating PGI 2 production.— Murray, J., Whitson, R. H., Itakura, K. Reduced prostaglandin I2 signaling in Arid5b −/− primary skeletal muscle cells attenuates myogenesis. FASEB J. 32, 1868–1879 (2018). www.fasebj.org