2811-LB: Liraglutide-Modified BMSCs Ameliorate Osteoporosis in Type 2 Diabetic Rats

Introduction and Objective: Diabetic osteoporosis (DOP) is a prevalent complication of diabetes mellitus associated with high morbidity and disability rates. Liraglutide, a glucagon-like peptide-1 receptor agonist, has emerged as a promising therapeutic agent for type 2 diabetes mellitus (T2DM) and may exert beneficial effects on bone metabolism. However, its potential role in modulating bone marrow mesenchymal stem cells (BMSCs) for the treatment of DOP remains unclear. Therefore, this study aimed to investigate whether liraglutide ameliorates osteoporosis in T2DM rats by regulating genetically modified BMSCs. Methods: Fifty rats were divided into control, T2DM induced by a combination of a high-fat diet and 35 mg/kg streptozotocin, T2DM-liraglutide (T2DM treated with 0.6mg/kg/day liraglutide), T2DM-BMSCs(T2DM treated with weekly 1.5×107/mL BMSCs suspension) and T2DM-BMSCs-liraglutide (T2DM treated with weekly liraglutide-modified BMSCs) groups. After 8 weeks of treatment, femurs and blood samples were obtained for subsequent investigations. Results: Diabetic rats exhibited altered bone metabolism, characterized by increased serum C-telopeptide of type I collagen (CTX-1) and decreased Procollagen type I N-terminal propeptide (PINP) and Runt-related transcription factor 2 (RUNX2) levels. Histological and micro-CT analyses revealed impaired bone structure, accompanied by enhanced osteoclast activity on TRAP staining and reduced RUNX2 immunoreactivity. These pathological changes were substantially ameliorated by treatment with liraglutide, BMSCs, or their combination. Notably, combination therapy with liraglutide-modified BMSCs demonstrated superior efficacy in restoring bone mass, inhibiting osteoclastogenesis, and promoting osteogenic marker expression compared to monotherapy. Conclusion: Liraglutide-modified BMSCs offer enhanced therapeutic benefits over monotherapy in DOP, underscoring their clinical potential as a priority intervention for patients with diabetes-associated bone loss. Disclosure S. Ge: None.