Hyperglycemia alters B cell subsets contributing to osteoarthritis progression

Hyperglycemia and osteoarthritis frequently coexist as comorbid conditions, and both are characterized by chronic low-grade inflammation driven by aberrant B cell differentiation. However, the interplay between hyperglycemia, osteoarthritis, and aberrant B cell function has yet to be fully elucidated. Peripheral blood samples were obtained from 100 osteoarthritis patients at various clinical stages (including 50 with normoglycemia and 50 with hyperglycemia), as well as from 20 healthy controls. Peripheral blood mononuclear cells were isolated, and B cell subset distributions were analyzed by flow cytometry. Multiplex immunofluorescence staining was performed to confirm aberrant synovial B cell populations in KOA patients with hyperglycemia. Additionally, in vitro experiments were conducted to assess the relationships among B cell activation, hyperglycemic conditions, and cartilage injury. Our study revealed that patients with hyperglycemia exhibited an overall increase in peripheral B cell counts, characterized by a significant reduction in regulatory B cells and a concomitant rise in memory B cells. Notably, the proportion of B cells in peripheral blood was positively correlated with the severity of joint degeneration. Consistently, we observed a substantial accumulation of activated B cells (CD86 +) within the synovium of patients with advanced knee osteoarthritis (KOA). In vitro, exposure to a high-glucose environment promoted chondrocyte injury, as indicated by reduced COL2A1 expression and elevated MMP13 levels; this deleterious effect was further exacerbated by the presence of B cells. These findings identify aberrant B cell responses as a key link between hyperglycemia-associated metabolic conditions and osteoarthritis progression, suggesting that targeting B cell-mediated inflammation may offer new therapeutic opportunities for patients with metabolic comorbidities.