Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Objective To explore the effectiveness of ipsilateral autologous semitendinosus ten don graft in treatment of lateral ankle ligament injuries and ankle instability. Methods Two patients including one male (25 years old) and one female (17 years old) with chronic lateral instability of the ankle were enrolled in the study. Both patients had the history of repeated ankle sprain in supination position and had grade Ⅲ injury of the lateral ankle ligament according to the American College of Foot and Ankle Surgeons Grading System. Anterior drawer test and talar tilt test were all positive. The stress-inversion radiograph demonstrated the average inclination of the talus for 21 ° and the lateral radiograph demonstrated anterior dislocation of the talus. The chronic ankle instabilities in two patients were treated by using the ipsilateral autologous semitendinosus tendon graft to reconstruct the lateral ankle ligament. Results The two patients were followed up for mean eight months, which revealed that the active and passive range of motion was good, with no pain or swelling. The anterior drawer test and talar tilt test were all negative. The stress-inversion radiograph demonstrated that the average inclination of the talus was less than 5°, with no anterior dislocation of the talus. According to the Mazur grading system, the clinical outcome was excellent in one patient and good in one. The two patients were satisfied with the stability of the ankle. Conclusions ( 1 ) Lateral ankle ligament injury is a common cause of chronic ankle instability,even the ankle osteoarthritis. ( 2 ) Brostr(o)m method can attain satisfactory result for fresh lateral injury of the ankle, but not for the old injuries. ( 3 ) Ipsilateral autologous semitendinosus tendon graft is simpleand effective for treatment of lateral ankle ligament injuries and chronic ankle instability and may play an important role in the treatment of lateral ankle instability and prevention of the occurrence of ankle osteoarthritis.