Inhibition of PKM2 suppresses osteoclastogenesis and alleviates bone loss in mouse periodontitis.

BACKGROUND: Chronic periodontitis triggers an increase in osteoclastogenesis, with glycolysis playing a crucial role in this process. Pyruvate kinase M2 (PKM2) is a critical enzyme involved in glycolysis and pyruvate metabolism. Yet, the precise function of PKM2 in osteoclasts and their formation remains unclear and requires further investigation. METHODS: Bioinformatics was used to investigate critical biological processes in osteoclastogenesis. In vitro, osteoclastogenesis was analyzed using tartrate-resistant acid phosphatase (TRAP) staining, phalloidin staining, quantitative real­time PCR (RT-qPCR), and Western blotting. Small interfering RNA (siRNA) of PKM2 and Shikonin, a specific inhibitor of PKM2, were used to verify the role of PKM2 in osteoclastogenesis. The mouse model of periodontitis was used to assess the effect of shikonin on bone loss. Analyses included micro computed tomography, immunohistochemistry, flow cytometry, TRAP staining and HE staining. RESULTS: Bioinformatic analysis revealed a significant impact of glycolysis and pyruvate metabolism on osteoclastogenesis. Inhibition of PKM2 leads to a significant reduction in osteoclastogenesis. In vitro, co-culture of the heat-killed Porphyromonas gingivalis significantly promoted osteoclastogenesis, concomitant with an increased PKM2 expression in osteoclasts. Shikonin weakened the promoting effect of porphyromonas gingivalis on osteoclastogenesis. In vivo experiments demonstrated that inhibition of PKM2 by shikonin alleviated bone loss induced by periodontitis, suppressed excessive osteoclastogenesis in alveolar bone, and reduced tissue inflammation to some extent. CONCLUSION: PKM2 inhibition by shikonin, a specific inhibitor of this enzyme, attenuated osteoclastogenesis and bone resorption in periodontitis. Shikonin appears to be a promising therapeutic agent for treating periodontitis.

The relationship between third molar agenesis and craniofacial morphology: a systematic review and meta-analysis.

BACKGROUND: Agenesis of third molar agenesis has a higher incidence than other tooth development anomalies. Previous research identified a potential correlation between third molar agenesis and specific craniofacial morphology; however, no systematic review and meta-analysis on this topic currently exists. OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the association between third molar agenesis and craniofacial sagittal and vertical morphology. SEARCH METHODS: An electronic search was conducted on PubMed, Embase, Web of Science, and the Cochrane Library without restrictions on publication year or language; this was supplemented by the manual retrieval of relevant literature. SELECTION CRITERIA: Cross-sectional studies that compared craniofacial morphology using angular and linear measurements obtained from lateral cephalography between patients with third molar agenesis and those without were included. DATA COLLECTION AND ANALYSIS: The quality assessment of the enrolled articles was evaluated by the Joanna Briggs Institute critical appraisal tool. Meta-analysis and sensitivity analysis were performed by Review Manager software (The Cochrane Collaborative, version 5.4, Cochrane IMS). RESULTS: A total of seven studies were included. Meta-analysis demonstrated that the ANB (mean differences (MD) = -0.75, 95% CI: -1.31 to -0.19, P < 0.01), palate length (ANS-PNS, MD = -1.68, 95% CI: -2.24 to -1.11, P < 0.01), and mandibular length (Go-Pog, MD = -0.36, 95% CI: -0.59 to -0.13, P < 0.01) were smaller in patients with third molar agenesis. With regard to vertical craniofacial morphology, the mandibular plane angle (MP-FH; MD = -1.88, 95% CI: -3.45 to -0.31, P = 0.02), gonial angle (gonial angle; MD = -1.73, 95% CI: -2.69 to -0.77, P < 0.01) and lower face height (lower face heigh angle; MD = -1.36, 95% CI: -1.94 to -0.77, P < 0.01) were smaller in patients with third molar agenesis, indicating a flatter or brachyfacial skeletal pattern. CONCLUSIONS: The results of this study suggest that third molar agenesis maybe associated with a reduced maxillary length and a flatter mandible. However, these findings need to be interpreted with caution due to inconsistencies in the certainty of evidence. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42023448226).

Influence of differences in mandibular incisor inclination on skeletal stability after orthognathic surgery in patients with skeletal Class III malocclusion.

OBJECTIVE: The preoperative inclination angle of mandibular incisors was crucial for surgical and postoperative stability while the effect of proclined mandibular incisors on skeletal stability has not been investigated. This study aimed to evaluate the effects of differences in presurgical mandibular incisor inclination on skeletal stability after orthognathic surgery in patients with skeletal Class III malocclusion. METHODS: A retrospective cohort study of 80 consecutive patients with skeletal Class III malocclusion who underwent bimaxillary orthognathic surgery was conducted. According to incisor mandibular plane angle (IMPA), patients were divided into 3 groups: retroclined inclination (IMPA < 87°), normal inclination (87° ≤ IMPA < 93°) and proclined inclination (IMPA ≥ 93°). Preoperative characteristics, surgical changes and postoperative stability were compared based on lateral cephalograms obtained 1 week before surgery (T0), 1 week after surgery (T1), and at 6 to 12 months postoperatively (T2). RESULTS: The mandible demonstrated a forward and upward relapse in all three groups. No significant differences in skeletal relapse were observed in the 3 groups of patients. However, the proclined inclination group showed a negative overbite tendency postoperatively compared with the other two groups and a clinically significant mandibular relapse pattern. Proclined IMPA both pre- and postoperatively was correlated with mandibular relapse. CONCLUSION: Sufficient presurgical mandibular incisor decompensation was of crucial importance for the maintenance of skeletal stability in patients with skeletal Class III malocclusion who subsequently underwent orthognathic surgery.

Effect of the lateral bone cut end on pattern of lingual split during bilateral sagittal split osteotomy in patients with skeletal class III malocclusion.

This study examines the effect of the lateral bone cut end (LBCE) on the pattern of lingual split during bilateral sagittal split osteotomy (BSSO) in patients with skeletal class III malocclusion. A case-control study according to the pattern of the sagittal split osteotomy (SSO) lingual split line was conducted in patients who underwent BSSO. The primary predictor variable was the ratio of the LBCE. The primary outcome variable was the type of lingual fracture line classified according to the lingual split scale (LSS). Other variables included patients' weight, sex, age, left and right sides of the mandible, and experience of the surgeon. Logistic regression analysis or the chi-squared test was performed to determine the effect of these variables on various types of lingual fracture line. The significance level was 95% (p < 0.05). There were 271 patients enrolled in this study. The SSO lingual split lines were divided into LSS1 (329/542), LSS2 (82/542), LSS3 (93/542), and LSS4 (38/542) splits. Logistic regression analysis showed that the LSS3 split was more likely to appear when the LBCE was closer to the lingual side (p = 0.0017). The age of patients significantly affected the possibilities of LSS2 (p = 0.0008) and LSS3 (p = 0.0023) splits. A LBCE close to the lingual side was an inducer for the formation of a LSS3 split in patients with skeletal class III malocclusion during BSSO. The age of the patient also affected the possibility of LSS2 and LSS3 splits.

Porphyromonas gingivalis Induces Bisphosphonate-Related Osteonecrosis of the Femur in Mice.

One of the most prominent characteristics of bisphosphonate-related osteonecrosis of the jaw(BRONJ) is its site-specificity. Osteonecrosis tends to occur specifically in maxillofacial bones, in spite of a systemic administration of the medicine. Previous studies suggested rich blood supply and fast bone turnover might be reasons for BRONJ. Yet, a sound scientific basis explaining its occurrence is still lacking. The present study aimed to explore the role of Porphyromonas gingivalis (P. gingivalis), an important oral pathogen, on the site-specificity of bisphosphonate-induced osteonecrosis and to elucidate its underlying mechanism. Mice were intraperitoneally injected with zoledronic acid (ZA) or saline for 3 weeks. In the third week, the right mandibular first molars were extracted and circular bone defects with a diameter of 1 mm were created in right femurs. After the operation, drug administration was continued, and P. gingivalis suspension was applied to the oral cavities and femur defects. The mice were killed after four or eight weeks postoperatively. The right mandibles and femurs were harvested for micro-CT and histological analyses. A poor healing of bone defects of both jaws and femurs was noted in mice injected with both ZA and P. gingivalis. Micro-CT analysis showed a decreased bone volume, and histological staining showed an increased number of empty osteocyte lacunae, a decreased collagen regeneration, an increased inflammatory infiltration and a decreased number of osteoclasts. In addition, the left femurs were collected for isolation of osteoclast precursors (OCPs). The osteoclastogenesis potential of OCPs was analyzed in vitro. OCPs extracted from mice of ZA-treated groups were shown to have a lower osteoclast differentiation potential and the expression level of related genes and proteins was declined. In conclusion, we established a mouse model of bisphosphonate-related osteonecrosis of both the jaw and femur. P. gingivalis could inhibit the healing of femur defects under the administration of ZA. These findings suggest that P. gingivalis in the oral cavity might be one of the steering compounds for BRONJ to occur.