Dasatinib and quercetin prevent alveolar bone loss in aged mice

BACKGROUND: Recent findings have associated alveolar bone loss (ABL) with the presence of senescent cells. Aging and the accumulation of senescent cells are associated with a pro-inflammatory environment which may exacerbate tissue damage. Senolytics(definition), such as dasatinib and quercetin (D&Q), eliminate senescent cells, offering potential therapeutic benefits. We evaluated the effects of D&Q on ABL during physiological aging and experimental periodontitis. METHODS: This study evaluated the effects of D&Q in two in vivo models: aging and ligature-induced periodontitis. In the aging model, 24 male C57BL/6 mice were allocated to CTRL (control-30 weeks of age), AGED (vehicle-treated, euthanized after 10 months), or D&Q (monthly gavage of D&Q [5 mg/kg and 50 mg/kg] for 10 months). In the periodontitis model, 24 Wistar rats (12 weeks old) were divided into CTRL, EP (experimental periodontitis, ligature + P. gingivalis), or D&Q (EP + weekly D&Q at 5 mg/kg and 50 mg/kg). The ABL and bone microarchitecture were assessed by microcomputed tomography and histomorphometry, and gene expression was also analyzed. The microarchitecture of the femurs was evaluated for systemic effects. RESULTS: In aged mice, D&Q reduced ABL, preserved the femoral cortical microarchitecture, and downregulated Il6, Mmp13 and Lamb1 expression. In contrast, D&Q failed to prevent ABL in the periodontitis model. CONCLUSION: D&Q treatment mitigated age-related bone loss; but did not prevent EP associated bone loss under the therapeutic regimen used. These results suggest that the effects of senolytic therapy depend on disease context and treatment conditions. PLAIN LANGUAGE SUMMARY: Aging increases the risk of periodontitis due to immune decline, chronic inflammation, and the accumulation of senescent cells, which release inflammatory factors that damage tissues. Senolytic drugs, such as dasatinib and quercetin (D&Q), selectively eliminate senescent cells and have shown promise in age-related diseases. In this study, we tested whether D&Q could reduce alveolar bone loss associated with aging or experimental periodontitis. The D&Q treatment protected aged mice by reducing bone loss, but it failed to prevent bone loss in the periodontitis model. These results suggest that the benefits of senolytic therapy may depend on disease context and treatment conditions.