Fine particulate matter accelerates the senescence of bone marrow-conserved stem cells in a type 2 diabetes mellitus mouse model.

Fine particulate matter (PM, diameter < 2.5 μm) is a significant public health concern because it can disrupt the bone marrow (BM) microenvironment through oxidative stress and systemic inflammation. Patients with type 2 diabetes mellitus (T2DM) exhibit heightened vulnerability to environmental stressors such as PM2.5, which exacerbates metabolic dysfunction. However, the effects of PM2.5 on BM resident stem cells in the context of diabetes have not been explored. In this study, we investigated the impact of atmospherically relevant PM2.5 exposure on BM-resident stem cells in T2DM mice. Diabetes and non-diabetes mice were exposed to artificial PM2.5 in an atmospheric simulation chamber (ASC) replicating real-world conditions. PM2.5 exacerbated tissue damage in the lung and liver by elevating levels of proinflammatory cytokines and disrupting pancreatic insulin-glucagon homeostasis. Additionally, PM2.5 skewed the BM microenvironment toward an aged phenotype, marked by mesenchymal stem cell (MSC) senescence and preferential adipogenesis over osteogenesis. Further, hematopoietic stem cells (HSCs) in T2DM mice exhibited enhanced senescence and functional deficits in clonogenic capacity and repopulation potential compared to those from wild-type (WT) mice. The deleterious effects of PM2.5 on MSCs and HSCs in T2DM were reversed by an NLR family pyrin domain-containing 3 (NLRP3) inhibitor, which ultimately maintains BM homeostasis. These findings indicate that PM2.5 exacerbates T2DM-induced BM stem cell dysfunction, at least in part by activating the NLRP3 inflammasome, revealing a synergistic interaction between environmental pollutants and metabolic disease.