Abstract 2466 Ablating Ogt in the Lepr+ BMSCs relieved the age-related bone loss in mice

Bone marrow stromal cells (BMSCs), serving as the source of osteoblasts, play a crucial role in bone growth, development, and associated diseases. The remodeling they undergo is vital for healthy aging. However, the mechanisms behind age-dependent bone remodeling remain largely unknown. In this study, utilizing micro-CT scans of mouse femurs, we establish that inhibiting the intracellular O-linked β-N-acetylglucosamine (O-GlcNAc), a form of posttranslational modification, in the leptin receptor-expressing (Lepr+) BMSCs can facilitate bone remodeling in aged mice. Through the Cre-loxP system mediated knockout of O-GlcNAc transferase (OGT) in Lepr+ BMSCs, we observed a significant increase in trabecular bone thickness and enlarged trabecular separation, with no apparent impact on overall bone mass. Our findings indicate that the ablation of OGT in BMSCs results in a thicker and sparser phenotype of trabecular bones in aged mice, suggesting that O-GlcNAc plays a role in the age-dependent remodeling of trabecular bone in mice. This work was supported by Department of Integrative Biology and Physiology Grant Accelerator Program to H.-B.R.