LNC297 Enhances the Differentiation of BMSCs and Mitigates BHBA-Induced Inhibition Through the Novel-miR-145/GAS7 Axis

The skeletal muscle tissue of dairy cows plays a crucial role in energy metabolism and is the site of β-hydroxybutyrate (BHBA) metabolism. However, the regulatory mechanism of BHBA in muscle differentiation remains unclear. This study used bovine skeletal muscle satellite cells (BMSCs) to investigate the effects of BHBA on the differentiation of bone marrow mesenchymal stem cells and to explore the regulatory roles of LNC297, novel-miR-145, and GAS7 in this process. The results of dual-luciferase reporter gene assays and miRNA pull-down experiments verified the targeting relationship between LNC297, novel-miR-145, and GAS7. BHBA inhibits the differentiation of BMSCs in a dose-dependent manner. Both LNC297 and GAS7 promote the differentiation of BMSCs and attenuate the inhibitory effect of BHBA. In contrast, novel-miR-145 inhibits BMSCs differentiation and enhances the inhibitory effect of BHBA. Mechanistically, LNC297 acts as a competing endogenous RNA (ceRNA) or molecular sponge for novel-miR-145, thereby upregulating GAS7 expression and promoting its differentiation function. Impaired muscle development in ketosis dairy cows is associated with the accumulation of high concentrations of BHBA in muscle tissue. LNC297 may promote muscle differentiation through the novel-miR-145/GAS7 axis, thereby alleviating muscle damage in ketosis cows. These findings provide new insights into the mechanisms of muscle development disorders in ketosis dairy cows.