MSTN^Del73C Mutation Modulates Glycerophospholipid Metabolism During Osteogenic Differentiation of Sheep BMSCs

Myostatin (MSTN) is a well-established negative regulator of skeletal muscle growth; however, its role in bone metabolism and osteogenic differentiation remains incompletely understood. In this study, untargeted and targeted metabolomic analyses were performed to investigate the metabolic effects of the MSTN^Del73C mutation during osteogenic differentiation of sheep bone marrow mesenchymal stem cells (BMSCs). Metabolomic profiles were analyzed in wild-type and MSTN^Del73C mutant BMSCs at 0, 7, and 14 days of osteogenic induction. During normal osteogenic differentiation, metabolites related to glycerophospholipid metabolism were repeatedly detected among significantly altered features, accompanied by marked increases in multiple lysophospholipid subclasses, including lysophosphatidylcholine (LPC), lysophosphatidylserine (LPS), and lysophosphatidylinositol (LPI). In contrast, MSTN^Del73C mutation was associated with significant reductions in several LPC and LPI species (p < 0.01 or p < 0.001), suggesting altered lipid metabolic profiles during differentiation. Targeted metabolomic validation further confirmed the altered abundance pattern of LPC 18:2. Collectively, these findings suggest that MSTN mutation is closely associated with metabolic remodeling during osteogenic differentiation and suggest potential involvement of glycerophospholipid-related metabolites involved in MSTN-related regulation of sheep BMSC osteogenesis.