Senescent Tregs Affect Osteogenesis Repair By Down-Regulating PGRN

Our research focuses on exploring the impact of senescent Tregs on bone repair function in mice and their related mechanisms. Initially, the repair capacity of skull defects and the aging status of Tregs were compared between a young group and an aging group. The aging Tregs was induced using D-gal, and the conditioned medium was extracted for in vitro co-culture with MC3T3-E1s to compare differences in osteogenic differentiation potential. Proteomic mass spectrometry analysis and Co-IP experiments were employed to investigate the related mechanisms and downstream pathways of senescent Tregs in modulating osteogenic differentiation, which were further validated by in vivo experiments. In vivo and in vitro experiments have revealed that aging Tregs inhibit the osteogenic differentiation of MC3T3-E1 to some extent, thereby affecting the bone repair ability of mice. Further studies have shown that PGRN regulates the bone repair process in mice through the EGFR/PI3K/AKT signaling pathway. A decrease in progranulin (PGRN) secreted by senescent Treg cells is one of the key factors leading to impaired osteogenic differentiation. The osteogenic differentiation ability of aged Tregs-CM in mice can be restored by supplementing with rPGRN. PGRN represents a potential therapeutic target for enhancing bone repair in elderly patients. Studies on PGRN are of great clinical significance, as they provide insights that can inform the development of new therapeutic programs and medication policies to promote bone formation in bone tissue.