Metformin Reduces Bone Resorption in Apical Periodontitis Through Regulation of Osteoblast and Osteoclast Differentiation.

INTRODUCTION: We have previously demonstrated that auxiliary metformin therapy promotes healing of apical periodontitis. Here we aimed to investigate the effects of metformin on osteoblast differentiation and osteoclast formation in cultured cells and rat apical periodontitis. METHODS: Murine pre-osteoblasts MC3T3-E1 and macrophages RAW264.7 were cultured under hypoxia (2% oxygen) or normoxia (21% oxygen) and stimulated with receptor activator of nuclear factor-κB ligand (RANKL) when indicated. Metformin was added to the cultures to evaluate its anti-hypoxic effects. Expressions of osteoblast differentiation regulator runt-related transcription factor 2 (RUNX2), RANKL, and osteoclast marker tartrate-resistant acid phosphatase (TRAP) were assessed by Western blot. Apical periodontitis was induced in mandibular first molars of 10 Sprague-Dawley rats. Root canal therapy with or without metformin supplement was performed. Periapical bone resorption was measured by micro-computed tomography. Immunohistochemistry was used to examine RUNX2, RANKL, and TRAP expressions. RESULTS: Hypoxia suppressed RUNX2 expression and enhanced RANKL synthesis in pre-osteoblasts. TRAP production increased in macrophages after hypoxia and/or RANKL stimulation. Metformin reversed hypoxia-induced RUNX2 suppression and RANKL synthesis in pre-osteoblasts. Metformin also inhibited hypoxia and RANKL-enhanced TRAP synthesis in macrophages. Intracanal metformin diminished bone loss in rat apical periodontitis. Comparing with vehicle control, cells lining bone surfaces in metformin-treated lesions had significantly stronger expression of RUNX2 and decreased synthesis of RANKL and TRAP. CONCLUSIONS: Alleviation of bone resorption by intracanal metformin was associated with enhanced osteoblast differentiation and diminished osteoclast formation in rat apical periodontitis. Our results endorsed the role of metformin as an effective medicament for inflammatory bone diseases.

Differences between the temporal and mandibular components of the temporomandibular joint in topographic distribution of osseous degenerative features on cone-beam computerized tomography.

BACKGROUND/PURPOSE: Temporomandibular joint osteoarthritis (TMJOA) pathology is characterized by degenerative changes of the subchondral bone. The topographic distribution of osseous degenerative changes in TMJ is not clear. This study aimed to evaluate the topographic distribution of osseous degenerative features in the TMJ by using cone-beam computerized tomography (CBCT). MATERIALS AND METHODS: The CBCT images of 26 female patients diagnosed to have TMJOA were retrieved from the database of the National Taiwan University Hospital. The images of left and right TMJs were evaluated independently by 2 examiners. The evaluated degenerative features included surface erosion, subcortical cysts, subcortical sclerosis, and osteophytes in the mandibular condyle and temporal component of the TMJ. The topographic distribution at different portions in the mandibular condyle and temporal component of the TMJ was statistically analyzed. RESULTS: Significant differences in the topographic distribution of the osseous degenerative features were observed (a) between the mandibular condyle and the temporal component and (b) between the anterior/central portion and posterior portion of the temporal component. No significant differences were observed in the topographic distribution of the TMJOA features in the condyle, except for surface erosion between the central and lateral portion of the condyle. CONCLUSION: The results suggest that the mandibular condyle and temporal component react differently in TMJ osseous degeneration, with the condyle being more vulnerable than the temporal component. Mandibular activities that require the mandibular condyle to function outside the fossa may be more destructive to the health and integrity of the TMJ.