Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disorder characterized by multisystem complications, among which abnormal bone metabolism constitutes a prominent clinical challenge. Periostin (POSTN) plays a pivotal role in regulating the survival, adhesion, differentiation, and proliferation of osteoblasts and mesenchymal stem cells, thereby maintaining bone biomechanical integrity, mediating mechanotransduction, and facilitating fracture healing. The present study aimed to investigate POSTN expression in the T2DM microenvironment and elucidate its functional role and underlying mechanisms in the osteogenic differentiation of bone marrow mesenchymal stem cells derived from T2DM rats (T2DM-BMSCs). BMSCs were isolated from normal Sprague-Dawley (SD) rats and T2DM-SD rats, respectively. The POSTN expression was quantified using RT-qPCR and ELISA, while cell viability was evaluated via live/dead cell staining. Cellular senescence was assessed through DCFH-DA fluorescent probe staining for ROS accumulation and β-galactosidase staining. Autophagic capacity was determined using MDC fluorescent probes combined with WB analysis. The osteogenic differentiation potential was evaluated by ALP staining, alizarin red S staining, as well as RT-qPCR and WB analysis of osteogenic marker genes/proteins. Compared with normal BMSCs, T2DM-BMSCs exhibited significantly downregulated POSTN expression levels. Lentiviral-mediated POSTN knockdown via r-Postn shRNA resulted in reduced cell viability, elevated intracellular ROS production, accelerated cellular senescence, and impaired autophagic activity and osteogenic differentiation potential in both T2DM-BMSCs and BMSCs. Conversely, exogenous POSTN supplementation enhanced cell viability, mitigated ROS accumulation, alleviated cellular senescence, and ameliorated autophagic flux and osteogenic capacity in these cells. In conclusion, POSTN modulates the osteogenic differentiation of T2DM-BMSCs and normal BMSCs through the regulation of autophagic processes and cellular senescence, highlighting its potential as a therapeutic target for ameliorating bone metabolism disorders in T2DM.
