Chronic Excessive Exercise Aggravates Apical Periodontitis in Mice

Abstract

AIM: To investigate the effects of overtraining on the development of apical periodontitis (AP) in mice. METHODOLOGY: Sixty 6-week-old male C57BL/6 mice were allocated to six groups: sedentary without AP (SED); sedentary with AP (SED AP); aerobic training without AP (AERO); aerobic training with AP (AERO AP); overtraining without AP (OVER); and overtraining with AP (OVER AP). The exercise protocols lasted 8 weeks, with AP induced in the fourth week by coronal opening of the lower first molars. At the end of the experiment, physical performance was assessed, together with periradicular bone resorption by micro-computed tomography, inflammatory infiltrate density, the number of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclasts and immunostaining for IL-6, TNF-α and IL-10. Gene expression of cytokines and markers related to bone resorption (IL-1β, IL-6, TNF-α, RANKL, osteoprotegerin and cathepsin K) was analysed by RT-qPCR, and plasma levels of IL-1β, IL-6, IL-10 and TNF-α were determined by multiplex immunoassay. RESULTS: The OVER and OVER AP groups showed a significant reduction in physical performance, supporting the induction of a chronic excessive exercise/non-functional overreaching-like state (p < 0.05). OVER AP group exhibited a higher volume of periradicular bone resorption compared with the AERO AP and SED AP groups (p < 0.05). Furthermore, the OVER AP group showed more intense inflammatory infiltrate, a higher number of TRAP+ cells and greater immunostaining for IL-6 and TNF-α than the AERO AP group (p < 0.05), but it did not differ from the SED AP group (p > 0.05). Gene expression of inflammatory and osteoclastogenic markers was higher in groups with AP than in those without AP (p < 0.05), whereas no significant differences were observed among the different exercise intensities (p > 0.05). Osteoprotegerin expression showed no significant differences among the groups (p > 0.05). Analysis of plasma cytokine levels showed no effect of overtraining (p > 0.05). CONCLUSIONS: Chronic excessive exercise aggravated AP, resulting in greater periradicular bone resorption and loss of the protective adaptations associated with moderate aerobic exercise. Overtrained animals displayed an inflammatory and osteoclastic profile comparable to that of sedentary animals, but with a more severe periapical bone destruction pattern.

The authors' abstract, as published at the source. International Endodontic Journal, 2026 · DOI ↗