Periodontal ligament-associated protein-1 promotes osteoclastogenesis in mice by modulating TGF-ß1/Smad1 pathway.

BACKGROUND: Periodontal ligament-associated protein-1 (PLAP-1), an important target molecule of osteoarthritis research, may affect alveolar bone resorption. The aim of our study was to comprehensively and systematically detect the effect of PLAP-1 on alveolar bone resorption and the underlying mechanism in PLAP-1 knockout mouse models. METHODS: We used a PLAP-1 knockout (C57BL/6N-Plap-1-/- ) mouse model to investigate the effect of PLAP-1 on osteoclast differentiation and the underlying mechanism by adding Porphyromonas gingivalis lipopolysaccharide to stimulate bone marrow-derived macrophages. The effect of PLAP-1 on alveolar bone resorption and the underlying mechanism were studied using a ligature periodontitis model, with microcomputed tomography imaging, immunochemistry, and immunofluorescence. RESULTS: The in vitro analysis results demonstrated that PLAP-1 knockout significantly inhibited osteoclast differentiation under both normal and inflammatory conditions. Bioinformatic analysis, immunofluorescence, and co-immunoprecipitation showed colocalization and interaction between PLAP-1 and transforming growth factor beta 1 (TGF-ß1). The phosphorylation of Smad1 was reduced in the PLAP-1 knockout cells compared with that in the cells from wild-type mice. The in vivo analysis results demonstrated that PLAP-1 knockout decreased bone resorption and the levels of osteoclast differentiation markers in experimental periodontitis compared with those in wild-type mice. Immunofluorescence staining confirmed colocalization of PLAP-1 and TGF-ß1 in the experimental periodontitis model. The phosphorylation level of Smad1 was significantly reduced in PLAP-1 knockout mice compared with that in wild-type mice. CONCLUSIONS: This study revealed that the knockout of PLAP-1 inhibits osteoclast differentiation and decreases alveolar bone resorption through the TGF-ß1/Smad1 signaling pathway, which could serve as an innovative target for the prevention and treatment of periodontitis.

Effect of chewing gum on orthodontic pain in patients receiving fixed orthodontic treatment: a systematic review and meta-analysis.

OBJECTIVES: The objective of this systematic review and meta-analysis was to evaluate the effect of chewing gum on orthodontic pain and to determine the rate of bracket breakage associated with fixed orthodontic appliances. METHODS: This review and its reporting were performed according to the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Six electronic databases were searched up to March 16, 2023, to identify relevant studies that met the inclusion and exclusion criteria. Furthermore, grey literature resources were searched. The Cochrane Collaboration Risk of Bias tool 2 was used to assess the quality of the included studies. Meta-analysis was conducted using RevMan, and sensitivity analysis and publication bias analysis were performed using STATA software. GRADE tool was used to evaluate the certainty of evidence. RESULTS: Fifteen studies with 2116 participants were ultimately included in this review, and 14 studies were included in the meta-analysis. Compared with the blank group, chewing gum had a significant pain relieving effect at all times after fixation of the initial archwire (P ≤ 0.05). No significant difference was found between the chewing gum group and the analgesics group at any timepoints (P > 0.05). Only four studies evaluated the rate of bracket breakage and revealed that chewing gum did not increase the rate of bracket breakage. The sensitivity analysis showed that there was no significant difference in the pooled outcomes after the included studies were removed one at times, and Egger analysis revealed no significant publication bias in included studies (P > 0.05). CONCLUSIONS: Chewing gum is a non-invasive, low-cost and convenient method that has a significant effect on relieving orthodontic pain and has no effect on the rate of bracket breakage. Therefore, chewing gum can be recommended as a suitable substitute for analgesics to reduce orthodontic pain.

CYP81A68 confers metabolic resistance to ALS and ACCase-inhibiting herbicides and its epigenetic regulation in Echinochloa crus-galli.

Long-term and excessive herbicide use has led to some environmental concerns and especially, herbicide resistance evolution in weeds. Here, we confirmed acetolactate synthase (ALS) inhibiting herbicide penoxsulam resistance and cross resistance to acetyl-coenzyme carboxylase (ACCase) inhibiting herbicides (cyhalofop-butyl and metamifop) in a global weed Echinochloa crus-galli population resistant to these herbicides (R). Penoxsulam metabolism study indicated that degradation rate was significantly higher in R than susceptible E. crus-galli population (S). RNA-sequencing revealed that a cytochrome P450 (P450) gene, CYP81A68, expressed higher in R versus S. Rice seedlings overexpressing this CYP81A68 gene are resistant to penoxsulam, cyhalofop-butyl and metamifop, and penoxsulam resistance is due to enhanced metabolism via O-demethylation. Deletion analysis of the CYP81A68 gene promoter identified an efficient region, in which differential methylation of CpG islands occurred between R and S. Collectively, these results demonstrate that upregulation of E. crus-galli CYP81A68 gene endows generalist metabolic resistance to commonly used ALS- and ACCase-inhibiting herbicides in rice fields and epigenetic regulation may play a role in the resistance evolution. This research could contribute to strategies reducing herbicide environmental impacts by judicious selection of alternative herbicide and non-chemical control tactics.

Resistance to mesosulfuron-methyl in Beckmannia syzigachne may involve ROS burst and non-target-site resistance mechanisms.

Herbicide resistance to chemical herbicide is a global issue that presents an ongoing threat to grain production. Though it has been frequently implicated that the production of detoxification enzymes increased in resistance development, the mechanisms for overexpression of these genes employed by herbicide-resistant weeds remain complicated. In this study, a mesosulfuron-methyl resistant Beckmannia syzigachne population (R) was found to be cross-resistant to another herbicide pyriminobac-methyl. No known target-site mutations were detected in the R population. In contrast, the decreased uptake and enhanced metabolic rates of mesosulfuron-methyl were detected in the R than the susceptible (S) population. Two candidate ATP-binding cassette (ABC) transporter genes (ABCB25 and ABCC14) that were constitutively up-regulated in the R population were identified by RNA-sequencing and validated by RT-qPCR. Alteration of antioxidant enzyme activities and gene expressions implied that mesosulfuron-methyl-induced antioxidant defenses provoked reactive oxygen species (ROS) burst. ROS scavenger assay showed that ROS induces ABCB25 and ABCC14 expression. This study reported for the first time that ABC transporters mediated non-target-site resistance contributes to mesosulfuron-methyl resistance in a B. syzigachne population, and implicated that ROS burst might be involved in the overexpression of ABC transporter genes in weeds.