Therapeutic potential of low-dose rosiglitazone in periodontitis: attenuation of inflammation and bone loss through macrophage reprogramming

This study aimed to investigate the effects of different dosages of the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist rosiglitazone on macrophage polarization, the expression of related inflammatory factors, and alveolar bone loss in the periodontal tissues of rats with experimental periodontitis, thereby providing experimental evidence supporting the potential use of rosiglitazone as a therapeutic agent for periodontitis. Forty rats were randomly assigned to four groups (n=10 per group): control group (C group), periodontitis group (P group), low-dose rosiglitazone treatment group (L group), and high-dose rosiglitazone treatment group (H group). After two weeks of rosiglitazone treatment via intraperitoneal injection, mandibles were scanned by micro-CT to quantify alveolar bone loss, with measurements of bone volume fraction (BV/TV), cemento-enamel junction to alveolar bone crest (CEJ-ABC) distance, and bone mineral density (BMD). Macrophages examined using immunofluorescence to quantify M1 and M2 proportions, and immunohistochemistry was performed to evaluate expression of IL-1β, IL-10 and osteoclast. Both the L and H groups significantly reduced the M1/M2 macrophage ratio and IL-1β expression in periodontal tissues compared to the P group (p<0.001), with no statistically significant differences observed between L and H groups. The L group exhibited a marked increase in M2 macrophage population and IL-10 expression relative to both the P and H groups (p<0.001). The number of osteoclasts was significantly lower in both L and H groups compared to the P group (p<0.0001), though no significant difference was detected between the L and H regimens. These findings were consistent with the Micro-CT analysis of BV/TV and CEJ-ABC distance. Notably, the BMD in the L group was significantly higher than that in both P (p<0.0001) and H (p<0.05) groups. Both low- and high-dose rosiglitazone effectively attenuated alveolar bone loss and mitigated associated periodontal tissue inflammation in experimental periodontitis by modulating macrophage polarization and regulating inflammatory cytokine expression. Notably, low-dose rosiglitazone may offer superior benefits in promoting tissue repair during the advanced stages of periodontal inflammation. Clinical relevance: Rosiglitazone demonstrates promising potential as a therapeutic agent for the clinical management of periodontitis.Keywords Experimental periodontitis, Rosiglitazone, Macrophage polarization, PPAR, Periodontal therapy.