Quantitative sensory testing of mandibular somatosensory function following orthognathic surgery-A pilot study in Chinese with class III malocclusion.

BACKGROUND: Somatosensory changes after sagittal split ramus osteotomy (SSRO) have not been fully studied in Chinese patients by the latest technologies. OBJECTIVE: To provide a comprehensive analysis of somatosensory function at the lower lip and chin at different time points following SSRO in a Chinese population. METHODS: A total of 22 patients (18-27 years; nine men) with skeletal III malocclusion and scheduled for SSRO were recruited. Quantitative sensory testing (QST) was performed at pre-operation (baseline), 1 week (1W), 1, 3 and 6 months (1M, 3M, 6M) post-operatively. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), mechanical detection threshold (MDT), mechanical pain threshold (MPT), pressure pain threshold (PPT) and two-point discrimination threshold (2PD) were tested at the lower lip and chin. RESULTS: Except for PPT at both test sides at 1W and 1M, all QST values indicated a significantly reduced sensitivity (p < .05). All values had returned to baseline values at 3M with exception of HPT at the right chin which, however, had recovered at 6M (p > .05). CONCLUSIONS: Somatosensory function at the lower lip and chin appears to be fully recovered in the majority of young Chinese adults 6 months after SSRO for skeletal class III malocclusion.

Skeletal Class III Malocclusion Is Associated with ADAMTS2 Variants and Reduced Expression in a Familial Case.

Skeletal Class III malocclusion with maxillary deficiency is a severe maxillofacial disease with unclear pathogenic mechanisms. We recruited a Han Chinese family who was clinically diagnosed with skeletal Class III malocclusion and maxillary deficiency. Using whole exome sequencing, a missense variant in ADAMTS2 (NM_014244: c.3506G>T: p.G1169V) was identified and predicted as deleterious by in silico tools. We also found ADAMTS2 variants associated with deficient maxillary development in a cohort. ADAMTS2 expression in HEK293 cells showed significant decrease due to the variant, which was also consistent in dental pulp stem cells from the proband and a healthy control. In the adamts2-knockdown zebrafish model, the length and width of the ethmoid plate, as well as the length of the palatoquadrate became significantly shorter than the control group (p < 0.001), while there was no significant difference in the length and width of the mandible. The expression of Sox3, which was required in early embryonic craniofacial development, was significantly downregulated in the adamts2-knockdown zebrafish embryos. Bioinformatic and cellular studies showed that the decreased expression of ADAMTS2 may inhibit downstream ErbB signaling pathway transduction and restrain subsequent osteogenesis in human adult mesenchymal stromal cells. Collectively, these data showed that ADAMTS2 (c.3506G>T: p.G1169V) may confer susceptibility to risk of skeletal Class III malocclusion with maxillary deficiency.

Effect of VEGFC on lymph flow and inflammation-induced alveolar bone loss.

The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. The effects of lymphatic drainage dysfunction on periodontitis have not been well studied. Here we show that lymphatic vessel endothelial receptor 1 (LYVE1)+ /podoplanin (PDPN)+ lymphatic vessels (LVs) are increased in the periodontal tissues, with accumulation close to the alveolar bone surface, in two murine periodontitis models: rheumatoid arthritis (RA)-associated periodontitis and ligature-induced periodontitis. Further, PDPN+ /alpha-smooth muscle actin (αSMA)- lymphatic capillaries are increased, whereas PDPN+ /αSMA+ collecting LVs are decreased significantly in the inflamed periodontal tissues. Both mouse models of periodontitis have delayed lymph flow in periodontal tissues, increased TRAP-positive osteoclasts, and significant alveolar bone loss. Importantly, the local administration of adeno-associated virus for vascular endothelial growth factor C, the major growth factor that promotes lymphangiogenesis, increases the area and number of PDPN+ /αSMA+ collecting LVs, promotes local lymphatic drainage, and reduces alveolar bone loss in both models of periodontitis. Lastly, LYVE1+ /αSMA- lymphatic capillaries are increased, whereas LYVE1+ /αSMA+ collecting LVs are decreased significantly in gingival tissues of patients with chronic periodontitis compared with those of clinically healthy controls. Thus, our findings reveal an important role of local lymphatic drainage in periodontal inflammation-mediated alveolar bone loss. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Flame Retardant Functionalization of Microcrystalline Cellulose by Phosphorylation Reaction with Phytic Acid.

The functionalization of microcrystalline cellulose (MCC) is an important strategy for broadening its application fields. In the present work, MCC was functionalized by phosphorylation reaction with phytic acid (PA) for enhanced flame retardancy. The conditions of phosphorylation reaction including PA concentration, MCC/PA weight ratio and temperature were discussed, and the thermal degradation, heat release and char-forming properties of the resulting PA modified MCC were studied by thermogravimetric analysis and pyrolysis combustion flow calorimetry. The PA modified MCC, which was prepared at 90 °C, 50%PA and 1:3 weight ratio of MCC to PA, exhibited early thermal dehydration with rapid char formation as well as low heat release capability. This work suggests a novel strategy for the phosphorylation of cellulose using PA and reveals that the PA phosphorylated MCC can act as a promising flame retardant material.

Surgery-First and Orthodontic-First Approaches Produce Similar Patterns of Condylar Displacement and Remodeling in Patients With Skeletal Class III Malocclusion.

PURPOSE: Condylar displacement and remodeling are critically involved in occlusal and skeletal stability after orthognathic surgery. The aim of the present study was to characterize condylar displacement and surface remodeling after bimaxillary orthognathic surgery in adult patients with skeletal Class III malocclusion treated by the surgery-first approach (SFA) or the orthodontic-first approach (OFA). MATERIALS AND METHODS: This retrospective cohort study recruited adult patients with mandibular hyperplasia treated with SFA or OFA. Simultaneous Le Fort I osteotomy for maxillary advancement and bilateral sagittal split ramus osteotomy for mandibular setback were performed in all patients. Original cone-beam computed tomographic data before surgery (T0), immediately after surgery (T1), and 12 months postoperatively (T2) were collected and reconstructed for 3-dimensional (3D) quantitative analyses. Three-dimensional condylar displacement and remodeling after SFA and OFA were characterized and statistically compared by Mann-Whitney U test and χ2 test. The significance level was set at a P value less than .05. RESULTS: Twenty-four (male-to-female ratio, 1:2; mean age, 21.2 yr) and 20 (male-to-female ratio, 1:1; mean age, 23.1 yr) patients were enrolled in the OFA and SFA groups, respectively. Condylar inferolateral displacement with inward and anterior rotations from T0 to T1 and return movements from T1 to T2 were observed regardless of treatment approach. Significantly greater amount of 3D bodily shift immediately after surgery (2.04 ± 1.05 mm in SFA group vs 1.22 ± 0.66 mm in OFA group; P < .05) and downward movement 1 year after surgery were observed in the SFA versus OFA group. Bone resorption in the condylar surface was prevalent and predominant in its lateral areas, whereas bone formation was frequently observed in the anteromedial area in the SFA (45%) and OFA (42.9%) groups. CONCLUSIONS: Similar patterns of 3D condylar displacement and surface remodeling were observed in patients treated with SFA or OFA.

Comparative Outcomes of Block and Cancellous Iliac Bone Grafting in Older Unilateral Alveolar Cleft Patients.

OBJECTIVE: To compare osseous outcomes of block and cancellous iliac bone grafting in older unilateral alveolar cleft patients. DESIGN: Retrospective and observational follow-up study. SETTING: Cleft Lip and Palate Centre, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China. PATIENTS: Forty-five nonsyndromic patients with unilateral complete alveolar cleft were enrolled in this study (25 patients in block bone graft group and 20 patients in cancellous bone graft group). INTERVENTIONS: In cancellous bone graft group, the alveolar cleft was filled with iliac cancellous bone particulate. In group of block bone graft, the harvested bone block was trimmed and fixed in alveolar defect. MAIN OUTCOME MEASURES: A novel method was proposed to investigate the volume and density of residual bone graft at 1-week, 3- and 6-month, 1- and 2-year postoperatively based on cone beam computed tomography scans. RESULTS: No difference in bone graft volume was found between 2 groups at 1-week and 3-month postoperatively; however, the residual volume of block bone graft group was significantly larger than that of cancellous bone graft group at 6-month, 1- and 2-year postoperatively. The bone density of block bone graft group was lower at 1-week and 3-month postoperatively but was comparable at 6-month, 1- and 2-year postoperatively. Our method was reliable and accurate to identify the range of residual bone graft when the boundary of grafted bone could not be identified clearly. CONCLUSION: Block bone graft could achieve comparable bone density and retain a greater amount of residual bone comparing to cancellous bone graft.

CBCT study on the relationship between lingula and antilingula position in a Chinese Han population.

OBJECTIVE: The purpose of this article was to assess the anatomical relationship between the lingula and the antilingula by measuring the projection of lingula on the lateral side of the ramus on CBCT. METHODS: This study collected CBCT images of 204 mandibular halves in 102 Chinese patients without any damage. We projected the lingula to the lateral side of the mandibular ramus and examined the distance and position relationship between the projection point and the antilingula using three-dimensional computed tomography (3DCT) created by image software. RESULTS: In 204 sides the antilingula appeared in 92 cases, 52 on right and 40 on left. The antilingula was used as a fixed point, in four cases the lingula projection in the anterior superior part, 38 cases in the posterior superior part, 45 cases in the posterior inferior part and zero case in the anterior inferior part. Scatter plots diagrammatic representation in four quadrants centered on the antilingula showed that 79% cases (73/92) lied in a 90° fan shape ranged in 5-10 mm radius in the posterior superior and inferior quadrant. CONCLUSION: The lingula mainly located in the posterior superior and inferior part from the antilingula in a 90° fan shape ranged in 5-10 mm radius. The osteotomy incision should be avoided in this area.

Imaging study on relationship between the location of lingula and the Gonial angle in a Chinese population.

PURPOSE: The purpose of this study was to investigate the Gonial angle in relation to the position of the lingula using computerized image analysis to guide the oral surgeons to prevent injury to the inferior alveolar nerve and peripheral blood vessels during surgery. METHODS: We measured Gonial angle sizes of bilateral rami and the distances from the lingula tip to the mandibular notch (LN), the anterior (LA) and posterior (LP) margin of the mandibular ramus, the mandibular base (LB) and the occlusive plane (h) in 407 Chinese adults with CBCT. RESULTS: In males, the mean distance of LN was 17.64 mm in the low Gonial angle group while 16.76 mm in the high Gonial angle group, which was significantly different between two groups (P < 0.001). The distance of LA in LGA group was obviously longer than that in HGA group (P < 0.001). The mean distance LP of men was 17.94 mm in LGA group while 16.9 mm in HGA group (P < 0.001). In females, the mean distance of LB in LGA group was 33.32 mm and 32.37 mm in HGA group (P < 0.01). CONCLUSION: We discovered that the segment of the mandibular branch, between the mandibular lingula and the mandibular angle, was obviously smaller in the HGA group than that in the LGA group.

Anatomical Study and Clinical Application of Facial Artery Perforator Flaps in Intraoral Reconstruction: Focusing on Venous System.

PURPOSE: Facial artery perforator flaps (FAPFs) are preferred for the repair of intraoral and peri-nasal defects because it is a convenient procedure with minimal donor-site morbidity. The purpose of this study was to investigate the anatomic features of FAPFs and present their clinical application in intraoral reconstruction. MATERIALS AND METHODS: Five cadaver specimens (10 sides) of the head and neck region and 90 clinical cases (90 sides) of neck dissection were analyzed to explore the facial venous drainage system of FAPFs. In addition, anatomic features of the facial artery and vein and the marginal mandibular branch of the facial nerve were investigated in cadaver specimens. Furthermore, the authors reviewed a series of 33 intraoral reconstruction cases using their designed FAPFs focusing on flap survival and facial venous drainage system types. RESULTS: Based on cadaveric and clinical observations, the facial vein drainage system was divided into 3 types: type A drained into the internal jugular vein (47%); type B drained into the external jugular vein (37%); and type C drained into the anterior jugular vein (16%). The mean distances from the facial artery to the vein at the region of the FAPF pedicle and tip were 2.79 ± 0.51 and 10.24 ± 0.70 mm, respectively. Most cases using the authors' designed FAPFs yielded satisfactory esthetic and functional outcomes, whereas 3 cases presented with venous congestion from type C facial vein drainage. CONCLUSION: This study improved the understanding of the anatomic features and clinical application of FAPFs in intraoral reconstruction. This FAPF design could be used to achieve superior intraoral defect reconstruction, and type C facial vein drainage might be a risk factor for flap survival.

Roles of SATB2 in site-specific stemness, autophagy and senescence of bone marrow mesenchymal stem cells.

Craniofacial bone marrow mesenchymal stem cells (BMSCs) display some site-specific properties that differ from those of BMSCs derived from the trunk and appendicular skeleton, but the characteristics of craniofacial BMSCs and the mechanisms that underlie their properties are not completely understood. Previous studies indicated that special AT-rich binding protein 2 (SATB2) may be a potential regulator of craniofacial skeletal patterning and site-specific osteogenic capacity. Here, we investigated the stemness, autophagy, and anti-aging capacity of mandible-derived BMSCs (M-BMSCs) and tibia-derived BMSCs (T-BMSCs) and explored the role of SATB2 in regulating these properties. M-BMSCs not only possessed stronger expression of SATB2 and stemness markers (pluripotency genes, such as Nanog, OCT-4, Sox2, and Nestin) but also exhibited stronger autophagy and anti-aging capacities under normal or hypoxia/serum deprivation conditions compared to T-BMSCs. Exogenous expression of SATB2 in T-BMSCs significantly enhanced the expression of pluripotency genes as well as autophagy and anti-aging capacity. Moreover, SATB2 markedly enhanced osteogenic differentiation of BMSCs in vitro, and promoted bone defect regeneration and the survival of BMSCs that were transplanted into mandibles with critical size defects. Mechanistically, SATB2 upregulates pluripotency genes and autophagy-related genes, which in turn activate the mechanistic target of rapamycin signaling pathway. Collectively, our results provide novel evidence that site-specific BMSCs have distinct biological properties and suggest that SATB2 plays a potential role in regulating the stemness, autophagy, and anti-aging properties of craniofacial BMSCs. The application of SATB2 to manipulate stem cells for the reconstruction of bone defects might represent a new approach.

Inverse colloidal crystal membranes for hydrophobic interaction membrane chromatography.

Hydrophobic interaction membrane chromatography has gained interest due to its excellent performance in the purification of humanized monoclonal antibodies. The membrane material used in hydrophobic interaction membrane chromatography has typically been commercially available polyvinylidene fluoride. In this contribution, newly developed inverse colloidal crystal membranes that have uniform pores, high porosity and, therefore, high surface area for protein binding are used as hydrophobic interaction membrane chromatography membranes for humanized monoclonal antibody immunoglobulin G purification. The capacity of the inverse colloidal crystal membranes developed here is up to ten times greater than commercially available polyvinylidene fluoride membranes with a similar pore size. This work highlights the importance of developing uniform pore size high porosity membranes in order to maximize the capacity of hydrophobic interaction membrane chromatography.

The interplay between alcohol consumption, oral hygiene, ALDH2 and ADH1B in the risk of head and neck cancer.

Alcohol consumption is an established risk factor for head and neck cancer (HNC). The major carcinogen from alcohol is acetaldehyde, which may be produced by humans or by oral microorganisms through the metabolism of ethanol. To account for the different sources of acetaldehyde production, the current study examined the interplay between alcohol consumption, oral hygiene (as a proxy measure for the growth of oral microorganisms), and alcohol-metabolizing genes (ADH1B and ALDH2) in the risk of HNC. We found that both the fast (*2/*2) and the slow (*1/*1+ *1/*2) ADH1B genotypes increased the risk of HNC due to alcohol consumption, and this association differed according to the slow/non-functional ALDH2 genotypes (*1/*2+ *2/*2) or poor oral hygiene. In persons with the fast ADH1B genotype, the HNC risk associated with alcohol drinking was increased for those with the slow/non-functional ALDH2 genotypes. For those with the slow ADH1B genotypes, oral hygiene appeared to play an important role; the highest magnitude of an increased HNC risk in alcohol drinkers occurred among those with the worst oral hygiene. This is the first study to show that the association between alcohol drinking and HNC risk may be modified by the interplay between genetic polymorphisms of ADH1B and ALDH2 and oral hygiene. Although it is important to promote abstinence from or reduction of alcohol drinking to decrease the occurrence of HNC, improving oral hygiene practices may provide additional benefit.

Graphene-based multilayers constructed from layer-by-layer self-assembly techniques.

This paper reviews the recent research and development of graphene-based multilayers fabricated from layer-by-layer (LBL) self-assembly technique. Graphene multilayer films, due to their excellent performances and specific applications, have attracted widespread attention during recent decades. In this paper, the preparation and property of self-assembled graphene multilayer films are introduced. The application of different graphene multilayer films in transparent conducting films (TCFs), field effect transistors (FETs), lithium ion batteries (LIBs), supercapacitors, and solar cells are summarized and discussed. The perspectives for the future developments of self-assembled graphene multilayer films are proposed.

A new design of facial artery perforator flaps for the reconstruction of small- to medium-sized intraoral defects.

AIM: The aim of this study was to investigate the reliability and outcomes of a new design of facial artery perforator flaps, extending from the angle of the mouth to the border of the mandible, for the reconstruction of small- to medium-sized intraoral defects. PATIENTS AND METHODS: The technique had been used in 23 patients between February 2009 and August 2012. The locations of intraoral defects included the tongue, the floor of the mouth, the inferior gingival mucosa, and the sublingual gland. All flaps were monitored for complications including skin loss and ischemia. The functions of appearance, swallowing, and speech were assessed 6 months after operation with the University of Washington Quality of Life Questionnaire. RESULTS: All flaps presented with satisfactory results except for one, which demonstrated superficial tip necrosis that settled after conservative treatment. The follow-up period ranged from 6 to 12 months, and 1 patient died as a result of pulmonary metastasis, and 3 patients underwent second surgery because of local tumor recurrence (2patients) and cervical recurrence (1 patient). Nineteen patients were assessed with the University of Washington Quality of Life Questionnaire, and the mean (SD) scores of appearance, swallowing, and speech were 57.89 (14.45), 83.68 (19.98), and 81.58 (23.16), respectively. CONCLUSIONS: This design of facial artery perforator flaps could provide an efficient and cost-effective method for reconstruction of small- to medium-sized intraoral defects with a low surgical morbidity and satisfactory levels of quality of life.

Injectable Thermosensitive Gel CH-BPNs-NBP for Effective Periodontitis Treatment through ROS-Scavenging and Jaw Vascular Unit Protection.

Periodontitis, a prevalent inflammatory condition in the oral cavity, is closely associated with oxidative stress-induced tissue damage mediated by excessive reactive oxygen species (ROS) production. The jaw vascular unit (JVU), encompassing both vascular and lymphatic vessels, plays a crucial role in maintaining tissue fluid homeostasis and contributes to the pathological process in inflammatory diseases of the jaw. This study presents a novel approach for treating periodontitis through the development of an injectable thermosensitive gel (CH-BPNs-NBP). The gel formulation incorporates black phosphorus nanosheets (BPNs), which are notable for their ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator that promotes lymphatic vessel function within the JVU. These results demonstrate that the designed thermosensitive gel serve as a controlled release system, delivering BPNs and NBP to the site of inflammation. CH-BPNs-NBP not only protects macrophages and human lymphatic endothelial cells from ROS attack but also promotes M2 polarization and lymphatic function. In in vivo studies, this work observes a significant reduction in inflammation and tissue damage, accompanied by a notable promotion of alveolar bone regeneration. This research introduces a promising therapeutic strategy for periodontitis, leveraging the unique properties of BPNs and NBP within an injectable thermosensitive gel.

Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization.

Alveolar bone regeneration has been strongly linked to macrophage polarization. M1 macrophages aggravate alveolar bone loss, whereas M2 macrophages reverse this process. Berberine (BBR), a natural alkaloid isolated and refined from Chinese medicinal plants, has shown therapeutic effects in treating metabolic disorders. In this study, we first discovered that culture supernatant (CS) collected from BBR-treated human bone marrow mesenchymal stem cells (HBMSCs) ameliorated periodontal alveolar bone loss. CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro. To clarify the underlying mechanism, the bioactive materials were applied to different animal models. We discovered macrophage colony-stimulating factor (M-CSF), which regulates macrophage polarization and promotes bone formation, a key macromolecule in the CS. Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats. Colony-stimulating factor 1 receptor (CSF1R) inhibitor or anti-human M-CSF (M-CSF neutralizing antibody, Nab) abolished the therapeutic effects of the CS of BBR-treated HBMSCs. Moreover, AKT phosphorylation in macrophages was activated by the CS, and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab. These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis. Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets. Overall, our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

An Injectable Black Phosphorus Hydrogel for Rapid Tooth Extraction Socket Healing.

The excess production of reactive oxygen species (ROS) will delay tooth extraction socket (TES) healing. In this study, we developed an injectable thermosensitive hydrogel (NBP@BP@CS) used to treat TES healing. The hydrogel formulation incorporated black phosphorus (BP) nanoflakes, recognized for their accelerated alveolar bone regeneration and ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator aimed at enhancing angiogenesis. In vivo investigations strongly demonstrated that NBP@BP@CS improved TES healing due to antioxidation and promotion of alveolar bone regeneration by BP nanoflakes. The sustained release of NBP from the hydrogel promoted neovascularization and vascular remodeling. Our results demonstrated that the designed thermosensitive hydrogel provided great opportunity not only for ROS elimination but also for the promotion of osteogenesis and angiogenesis, reflecting the "three birds with one stone" concept, and has tremendous potential for rapid TES healing.

Molecular events in the jaw vascular unit: A traditional review of the mechanisms involved in inflammatory jaw bone diseases.

Inflammatory jaw bone diseases are common in stomatology, including periodontitis, peri-implantitis, medication-related osteonecrosis of the jaw, radiation osteomyelitis of the jaw, age-related osteoporosis, and other specific infections. These diseases may lead to tooth loss and maxillofacial deformities, severely affecting patients' quality of life. Over the years, the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge. Therefore, exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial for improving prognosis and developing new targeted therapies. Accumulating evidence indicates that the integrated bone formation and dysfunction arise from complex interactions among a network of multiple cell types, including osteoblast-associated cells, immune cells, blood vessels, and lymphatic vessels. However, the role of these different cells in the inflammatory process and the 'rules' with which they interact are still not fully understood. Although many investigations have focused on specific pathological processes and molecular events in inflammatory jaw diseases, few articles offer a perspective of integration. Here, we review the changes and mechanisms of various cell types in inflammatory jaw diseases, with the hope of providing insights to drive future research in this field.

NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs.

NLRP3 has been involved in several physiological and pathological processes. However, the role and mechanism of NLRP3 activation in mandibular healing remain unclear. Here, a full-thickness mandibular defect model by osteotomy was established in wild-type (WT) and Prx1-Cre/ROSAnTnG mice to demonstrate the NLRP3 inflammasome activation in mandibular healing. We found that NLRP3 was activated in mesenchymal stem cells (MSCs)-mediated mandibular healing and was prominent in Prx1+ cells. Inhibition of NLRP3 exerted a positive effect on bone formation without changing the number of Prx1-cre+ cells in the defect areas. In addition, NLRP3 deficiency promoted osteoblast differentiation. We next screened for the deubiquitinating enzymes that were previously reported to be associated with NLRP3, and identified UCHL5 as a regulator of NLRP3 activation in mandibular healing. Mechanistically, NLRP3 directly bound to UCHL5 and maintained its stability through reducing ubiquitin-proteasome pathway degradation in mandibular MSCs. At last, UCHL5 inhibition enhanced osteoblast differentiation by promoting NLRP3 ubiquitination and degradation. Thus, our results provided the proof that NLRP3 acted as a negative modulator in mandibular healing and extended the current knowledge regarding posttranslational modification of NLRP3 by UCHL5.

Toxicity of sodium fluoride to Caenorhabditis elegans.

OBJECTIVE: To investigate the toxic effect of sodium fluoride (NaF) on the nematode Caenorhabditis elegans (C. elegans). METHODS: Adult C. elegans were exposed to different concentrations of NaF (0.038 mmol/L, 0.38 mmol/L, and 3.8 mmol/L) for 24 h. To assess the physiological effects of NaF, the brood size, life span, head thrashes, and body bend frequency were examined. Reactive oxygen species (ROS) and cell apoptosis were detected as parameters of biochemical response. The gene expressions were determined by real-time polymerase chain reaction (PCR) to assess the molecular-level response. RESULTS: At the physiological level, the brood size of C. elegans exposed to 0.038 mmol/L, 0.38 mmol/L, and 3.8 mmol/L concentrations of NaF were reduced by 6%, 26%, and 28% respectively in comparison with the control group. The maximum life spans of C. elegans exposed to 0.038 mmol/L, 0.38 mmol/L, and 3.8 mmol/L concentrations of NaF were reduced by 3 days and 5 days, respectively. Head thrashes and body bend frequency both decreased with increasing concentrations of NaF. At the biochemical level, the production of ROS and the incidence of cell apoptosis increased with increasing concentrations of NaF (P < 0.05). At the molecular level, different concentrations of NaF exposure raised the expression of stress-related genes, such as hsp16.1, sod-3, ctl-2, dhs-28, gst-1, and cep-1. CONCLUSION: NaF exposure could induce multiple biological toxicities to C. elegans in a concentration-dependent manner. These toxicities may be relevant to the oxidative stress induced by increased ROS production and accumulation in C. elegans.