Abstract
Background: Osteoporosis is a prevalent metabolic bone disorder, especially in individuals with diabetes. Recent studies suggest that GLP-1 plays a positive role in regulating bone metabolism. However, the impact of GLP-1R on bone marrow-derived mesenchymal stem cells, particularly STRO-1-positive BMSCs, remains unclear. This study aims to investigate the impact of GLP-1R activation on the osteogenic differentiation potential of STRO-1-positive BMSCs. Methods and results: BMSCs were isolated from the femurs and tibias of Sprague-Dawley rats, characterized by flow cytometry and immunofluorescence. The expression of osteogenic genes(COL-I, OCN, RUNX2) and osteoprotegerin(OPG) was assessed by qPCR and Western blot. Osteogenic differentiation was evaluated by alizarin red and alkaline phosphatase staining. The GLP-1R expression in STRO-1-positive and negative BMSCs was compared. Pharmacological interventions with GLP-1R agonists and antagonists were used to evaluate their effect on osteogenesis. The results show that STRO-1-positive BMSCs exhibited stronger osteogenic potential than STRO-1-negative BMSCs. GLP-1R activation enhanced osteogenesis, with the agonist group displaying the highest mineralization capacity despite showing lower osteogenic gene expression. The control group exhibited the highest gene expression but the weakest mineralization capacity. Furthermore, JNK/ERK mRNA and protein levels were reduced at varying degrees in the experimental groups. Conclusion: STRO-1-positive BMSCs exhibit stronger osteogenic potential, which may be facilitated through GLP-1R activity at varying levels, promoting their differentiation into mature osteoblasts.