GLUL mediates FOXO3 O-GlcNAcylation to regulate the osteogenic differentiation of BMSCs and senile osteoporosis

The abnormal osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is an important cause of senile osteoporosis (SOP). Glutamine synthetase (GLUL) is a key enzyme in glutamine biosynthesis; however, its functional role in SOP remains unclear. Here, we found that GLUL expression was downregulated in the BMSCs of SOP patients. BMSC-conditioned <i>Glul</i>-knockout (KO) mice exhibited dysplasia of the skull and phalanges and osteoporosis due to disordered osteogenic differentiation.