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

Skeletal muscle tissue in dairy cows undergoes significant alterations in cellular energy metabolism under ketosis conditions and represents an important site of β-hydroxybutyrate (BHBA) exposure and utilization. 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 BMSCs and to explore the regulatory roles of LNC297, 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, 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, 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 miR-145, thereby upregulating GAS7 expression and promoting its differentiation function. LNC297 may promote muscle differentiation through the miR-145/GAS7 axis, thereby alleviating muscle damage in dairy cows with ketosis. These findings provide new insights into the mechanisms of muscle development disorders in dairy cows with ketosis.