Cone beam computed tomography assessment of maxillary anterior teeth cervix dimensions in healthy adults for optimal anatomic healing abutments.

OBJECTIVES: The abutments produced with circular symmetry failed to accurately replicate the natural teeth's cervical shapes. The purpose of this study was to measure cervical cross-sections of maxillary anterior teeth using cone beam computed tomography (CBCT) images to design anatomic healing abutments. MATERIALS AND METHODS: CBCT data of 61 patients were analyzed using Ez3D Plus software. Measurements were taken at the cemento-enamel junction (CEJ) and 1 mm coronal to CEJ for maxillary central incisors, lateral incisors, and canines. Various parameters, including area, perimeter, and eight line segments in the distal (a), disto-palatal (b), palatal (c), mesio-palatal (d), mesial (e), mesio-labial (f), labial (g), and disto-labial (h) directions, were used to describe dental neck contours. The ratios (f/b and h/d) were analyzed, and differences based on sex and dental arch morphology were explored. RESULTS: Significant differences were found in area and perimeter between males and females, but not in f/b and h/d ratios. Differences in the f/b ratio were observed among dental arch morphologies for maxillary central incisors, lateral incisors, and canines. CONCLUSIONS: CBCT measurements of cervical cross-sections provide more accurate data for designing anatomic healing abutments. The fabrication of anatomical healing abutments needs to consider the influence of gender on cervical size and to explore the potential effect of arch shape on cervical morphology. CLINICAL SIGNIFICANCE: The novel method provides detailed measurements for the description of dental cervical contours for patients with bilateral homonymous teeth missing. The measurements of this study could be utilized to design more accurate anatomic healing abutments to create desired morphology of peri-implant soft tissue.

Does the incorporation of strontium into calcium phosphate improve bone repair? A meta-analysis.

BACKGROUND: The application of calcium phosphate (CaP)-based bone substitutes plays an important role in periodontal regeneration, implant dentistry and alveolar bone reconstruction. The incorporation of strontium (Sr) into CaP-based bone substitutes appears to improve their biological properties, but the reported in vivo bone repair performance is inconsistent among studies. Herein, we conducted a systematic review and meta-analysis to investigate the in vivo performance of Sr-doped materials. METHODS: We searched PubMed, EMBASE (via OVIDSP), and reference lists to identify relevant animal studies. The search, study selection, and data extraction were performed independently by two investigators. Meta-analyses and sub-group analyses were conducted using Revman version 5.4.1. The heterogeneity between studies were assessed by I2. Publication bias was investigated through a funnel plot. RESULTS: Thirty-five studies were finally enrolled, of which 16 articles that reported on new bone formation (NBF) were included in the meta-analysis, covering 31 comparisons and 445 defects. The overall effect for NBF was 2.25 (95% CI 1.61-2.90, p < 0.00001, I2 = 80%). Eight comparisons from 6 studies reported the outcomes of bone volume/tissue volume (BV/TV), with an overall effect of 1.42 (95% CI 0.65-2.18, p = 0.0003, I2 = 75%). Fourteen comparisons reported on the material remaining (RM), with the overall effect being -2.26 (95% CI - 4.02 to - 0.50, p = 0.0009, I2 = 86%). CONCLUSIONS: Our study revealed that Sr-doped calcium phosphate bone substitutes improved in vivo performance of bone repair. However, more studies are also recommended to further verify this conclusion.

Sclerostin inhibits odontogenic differentiation of human pulp-derived odontoblast-like cells under mechanical stress.

Sclerotic dentin is a natural self-protective barrier beneath non-carious cervical lesions (NCCLs), which are mainly induced by mechanical stress. Sclerostin is a mechanosensory protein and serves as an inhibitor of dentinogenesis. However, its function on mechanotransduction in dentine-pulp complex has not been elucidated yet. In this study, decreased sclerostin expression was detected in odontoblasts beneath NCCL-affected sclerotic dentin. Then human pulp-derived odontoblast-like cells (hOBs) were subjected to mechanical strain (MS) in vitro: the results showed that MS-induced upregulation of odontogenic differentiation markers (dentin sialophosphoprotein, osteopontin, osteocalcin, and runt-related transcription factor 2) in hOBs with downregulated sclerostin expression, and this inductive differentiation was attenuated when sclerostin was overexpressed. Additionally, MS activated ERK1/2 pathway and ERK1/2 inhibition restored MS-induced downregulation of sclerostin. Proteasome inhibitor MG132 could also rescue MS-induced decrease of sclerostin. Furthermore, MS suppressed STAT3 pathway, which could be reversed by sclerostin overexpression. STAT3 inhibition was shown to ameliorate the reduction of odontogenic markers induced by sclerostin overexpression. Taken together, we conclude that MS downregulates sclerostin expression via the ERK1/2 and proteasome signaling pathways to promote odontogenic differentiation of hOBs through the STAT3 signaling pathway. It can therefore be inferred that under mechanical stress, sclerostin inhibition promotes reactive dentin formation by enhancing odontogenic differentiation of odontoblasts, which might be one of potential forming mechanisms of sclerotic dentin beneath NCCLs.

Protective roles of FICZ and aryl hydrocarbon receptor axis on alveolar bone loss and inflammation in experimental periodontitis.

AIM: The aryl hydrocarbon receptor (AhR)-ligand axis has been shown to be involved in inflammatory diseases and bone homeostasis. However, the activation of AhR signalling pathway and the possible functions of AhR ligands in periodontitis are underexplored. This study investigated the expression of the AhR target gene cytochrome P450 subfamily B member 1 (CYP1B1) and the functions and mechanisms of the AhR ligand 6 formylindolo[3,2-b]carbazole (FICZ) in periodontitis. MATERIALS AND METHODS: CYP1B1 expression was detected in human periodontitis samples, mice with ligature-induced periodontitis and lipopolysaccharide (LPS)-induced inflammation in periodontal ligament cells (PDLCs) in vitro. FICZ was administered topically or systemically. The therapeutic functions of FICZ were detected via qPCR, micro-computed tomography and immunohistochemistry. Finally, the mechanisms of AhR signalling in periodontitis were investigated by cell assays. RESULTS: CYP1B1 expression was downregulated in periodontitis. FICZ rescued the alveolar bone loss and mitigated the inflammatory cytokines in periodontitis mice. In vitro, FICZ pre-treatment reduced the LPS-induced inflammation in PDLCs via the increased phosphorylation of STAT3. Additionally, FICZ prompted the mineralization of PDLCs via activation of the Wnt/ß-catenin signalling pathway. CONCLUSION: AhR signalling pathway is suppressed in periodontitis and the AhR ligand FICZ can prevent periodontitis.

Targeting G6PD to mitigate cartilage inflammation in TMJOA: The NOX4-ROS-MAPK axis as a therapeutic avenue.

Chondrocytes, known for their metabolic adaptability in response to varying stimuli, play a significant role in osteoarthritis (OA) progression. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, has recently been found to upregulate in OA chondrocyte. However, the exact role of G6PD in temporomandibular joint osteoarthritis (TMJOA) and its effect on chondrocyte function remains unclear. In present study, we induced OA-like conditions in the rat temporomandibular joint via occlusal disharmony (OD), noting a marked increase in G6PD expression in the condylar cartilage. Our data show that G6PD knockdown in mandibular condylar chondrocytes (MCCs) reduces the expression of catabolic enzymes (e.g., MMP3, MMP13) and inflammatory cytokines (e.g., IL6) induced by IL-1ß. G6PD knockdown also mitigates IL-1ß-induced upregulation of ERK, JNK, and p38 phosphorylation and reduces reactive oxygen species (ROS) levels by decreasing the nicotinamide adenine dinucleotide phosphate (NADPH) and NADPH oxidases 4 (NOX4) mRNA expression. In summary, G6PD appears to regulate the inflammatory state of condylar chondrocytes via the NOX-ROS-MAPK axis, highlighting its potential as a therapeutic target for TMJOA.

Correlation between peri-implant bone mineral density and primary implant stability based on artificial intelligence classification.

Currently, the classification of bone mineral density (BMD) in many research studies remains rather broad, often neglecting localized changes in BMD. This study aims to explore the correlation between peri-implant BMD and primary implant stability using a new artificial intelligence (AI)-based BMD grading system. 49 patients who received dental implant treatment at the Affiliated Hospital of Stomatology of Fujian Medical University were included. Recorded the implant stability quotient (ISQ) after implantation and the insertion torque value (ITV). A new AI-based BMD grading system was used to obtain the distribution of BMD in implant site, and the bone mineral density coefficients (BMDC) of the coronal, middle, apical, and total of the 1 mm site outside the implant were calculated by model overlap and image overlap technology. Our objective was to investigate the relationship between primary implant stability and BMDC values obtained from the new AI-based BMD grading system. There was a significant positive correlation between BMDC and ISQ value in the coronal, middle, and total of the implant (P < 0.05). However, there was no significant correlation between BMDC and ISQ values in the apical (P > 0.05). Furthermore, BMDC was notably higher at implant sites with greater ITV (P < 0.05). BMDC calculated from the new AI-based BMD grading system could more accurately present the BMD distribution in the intended implant site, thereby providing a dependable benchmark for predicting primary implant stability.

A technique for immediate implant placement in mandibular multirooted teeth by the aid of a dynamic guidance system and preparing implant bed before tooth extraction.

Due to site-specific anatomical challenges, traditional immediate dental implant placement for mandibular multirooted molar sizes has many limitations. This technical report describes a modified approach for immediate dental implant placement in molar sites allowing for precise three-dimensional (3D) implant position and favourable clinical effect with the aid of a dynamic guidance system and flapless pre-extractive preparation of the implant bed.

Effect of sulfonation time on physicochemical, osteogenic, antibacterial properties and biocompatibility of carbon fiber reinforced polyether ether ketone.

The carbon fiber reinforced polyetheretherketone (CFR-PEEK) has been increasingly used in orthopedics dentistry due to its excellent biocompatibility and mechanical properties. However, the biological inertness and poor antibacterial activity limit its clinical applications. This paper focused on the performances of CFR-PEEK with porous morphology that were exposed to different sulfonation periods (1, 3, 5, and 10 min, corresponding to CP-S1, CP-S3, CP-S5, and CP-S10, respectively). Residual sulfuric acid was removed by acetone rinsing, NaOH immersion, and hydrothermal treatment before in vitro and in vivo studies. The results showed some significant difference in the physicochemical properties, including energy dispersive X-ray spectroscopy (EDS) map of sulfur atoms, X-ray photoelectron spectroscopy (XPS) of valences of sulfur ions, Fourier transformation infrared spectroscopy (FTIR), hydrophilicity, hardness, and elastic modulus among CP-S3, CP-S5, and CP-S10. However, CP-S5 and CP-S10 were more effective in promoting the proliferation, adhesion, and osteogenic differentiation of seeded bone mesenchymal stem cells (BMSCs) and growth inhibition of S. aureus and P. gingivalis compared with other groups. Furthermore, the CP-S5 and CP-S10 samples achieved better cranial bone repair than the non-sulfonation group in a rat model. Therefore, it can be inferred that both 5 and 10 min are viable sulfonation durations for 30% CFR-PEEK. These findings provide a theoretical basis for developing CFR-PEEK for clinical applications.

BNTA attenuates temporomandibular joint osteoarthritis progression by directly targeting ALDH3A1: An in vivo and in vitro study.

BNTA is known to have a therapeutic effect on knee osteoarthritis and inflammatory osteoclastogenesis. However, the protective effect of BNTA regarding temporomandibular mandibular joint osteoarthritis (TMJOA) and its underlying mechanism and physiological target remains unclear. In the present study, BNTA ameliorated cartilage degradation and inflammation responses in monosodium iodoacetate (MIA)-induced TMJOA in vivo. In IL-1ß-induced condylar chondrocytes, BNTA prevents oxidative stress, inflammatory responses and increasing synthesis of cartilage extracellular matrix through activating nuclear factor-E2-related factor 2 (NRF2) signaling. Suppression of NRF2 signaling abolishes the protective effect of BNTA in TMJOA. Notably, BNTA may bind directly to ALDH3A1 and act as a stabilizer, as evidenced by drug affinity responsive target stability assay (DARTS), cellular thermal shift assay (CETSA) and molecular docking results. Further investigation of the underlying molecular and cellular mechanism infers a positive correlation of ALDH3A1 regulating NRF2 signaling. In conclusion, BNTA may attenuate TMJOA progression via the ALDH3A1/NRF2 axis, inferring that BNTA is a therapeutic target for treating temporomandibular mandibular joint osteoarthritis.

Cinnamaldehyde protects against ligature-induced periodontitis through the inhibition of microbial accumulation and inflammatory responses of host immune cells.

Cinnamaldehyde (CA), the main active ingredient in cinnamon, has been proved to be a potential candidate for controlling inflammation; however, there has been little evidence demonstrating its role in alleviating periodontitis. The aim of this study was to investigate the effect of orally administered CA on ligature-induced periodontitis in mice and the administration of CA on the Porphyromonas gingivalis (Pg) supernatant-induced inflammatory responses of murine macrophages and human periodontal ligament cells (HPDLCs). In vivo experiments showed that the oral administration of CA significantly inhibited bone resorption, the accumulation of anaerobic bacteria and host immuno-inflammatory responses in ligature-induced periodontitis in mice. In vitro, CA inhibited the expression of Pg supernatant-induced IL6, IL8, TNFA and IL1B and reactive oxygen species in RAW 264.7 and HPDLCs, involving the inactivation of the NFKB signaling pathway, which was activated by the Pg supernatant. Also, the expression of adherent and chemotactic-related cytokines was inhibited by CA, accompanied with a reduction in adherent HPDLCs. Moreover, CA ameliorated the cellular senescence of HPDLCs induced by H2O2, together with a decrease in senescence-associated-ß-galactosidase positive cells and decrease in the expression of P53, P21 and P16. Furthermore, CA promoted the osteogenic differentiation of HPDLCs with an increase in alkaline phosphatase expression and activity, formation of more mineralization nodules, and increased the expression of bone sialoprotein and osteopontin. Conclusions: Daily diet-added CA may be beneficial for oral health care, especially for the control of periodontic disease by suppressing the dysbiosis of biofilms and inhibiting the immunoinflammatory responses of migrated macrophages and local resident periodontal ligament cells to specific pathogen irritations.

High-throughput sequencing analysis of the expression profile of microRNAs and target genes in mechanical force-induced osteoblastic/cementoblastic differentiation of human periodontal ligament cells.

Mechanical tension force directs the lineage commitment of periodontal ligament cells (PDLCs) to osteogenesis; however, the underlying mechanisms, especially those at the post-transcriptional level, remain unclear. In the present study, we developed an in vitro force-loading model for PDLCs. Then, high-throughput sequencing was used to identify the expression profile of microRNAs (miRNAs) for stretched PDLCs. The candidate target genes of differentially expressed miRNAs were predicted by bioinformatics analysis. A total of 47 miRNAs were found to be differentially expressed in stretched and non-stretched PDLCs; of these, 31 were upregulated and 16 were downregulated. Further, 9 osteogenesis-related miRNAs (miR-221-3p, miR-138-5p, miR-132-3p, miR-218-5p, miR-133a-3p, miR-145-3p, miR-143-5p, miR-486-3p, and miR-21-3p) were validated by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were then carried out to reveal the potential functions of predicted target genes. Among the top 20 enriched pathways, the Hippo signaling pathway was selected for further functional analysis. Several important components of the Hippo signaling pathway, including YAP1, WWTR1, TEAD2, CTGF, DVL2, GDF5, GLI2, LIMD1, WTIP, LATS1, and TEAD1, were predicted to be target genes of differentially expressed miRNAs and were determined to be upregulated in stretched PDLCs. Among them, YAP1, WWTR1, TEAD2, CTGF, DVL2, and GDF5 were positive regulators of osteogenesis. These findings may provide a reliable reference for future studies to elucidate the biological mechanisms of orthodontic tooth movement (OTM).

Effects of sclerostin on lipopolysaccharide-induced inflammatory phenotype in human odontoblasts and dental pulp cells.

Previously we have demonstrated that sclerostin inhibits stress-induced odontogenic differentiation of odontoblasts and accelerates senescence of dental pulp cells (DPCs) Odontoblasts and DPCs are main functioning cells for inflammation resistance and tissue regeneration in dentine-pulp complex. Sclerostin is relevant for systemic inflammation and chronic periodontitis processes, but its effects on dental pulp inflammation remains unclear. In this study, we found that sclerostin expression of odontoblasts was elevated in lipopolysaccharide-induced inflammatory environment, and exogenous sclerostin increased the production of pro-inflammatory cytokines in inflamed odontoblasts. Furthermore, sclerostin activated the NF-κB signaling pathway in inflamed odontoblasts and the NF-κB inhibitor reversed the exaggerative effects of sclerostin on the pro-inflammatory cytokines production. Additionally, sclerostin promoted adhesion and migration of inflamed DPCs, while inhibiting odontoblastic differentiation of inflamed DPCs. Sclerostin also might enhance pulpal angiogenesis. Taken together, it can therefore be inferred that sclerostin is upregulated in inflamed odontoblasts under pulpal inflammatory condition to enhance inflammatory responses in dentine-pulp complex and impair reparative dentinogenesis. This indicates that sclerostin inhibition might be a therapeutic target for anti-inflammation and pro-regeneration during dental pulp inflammation.

Sclerostin promotes human dental pulp cells senescence.

BACKGROUND: Senescence-related impairment of proliferation and differentiation limits the use of dental pulp cells for tissue regeneration. Deletion of sclerostin improves the dentinogenesis regeneration, while its role in dental pulp senescence is unclear. We investigated the role of sclerostin in subculture-induced senescence of human dental pulp cells (HDPCs) and in the senescence-related decline of proliferation and odontoblastic differentiation. METHODS: Immunohistochemical staining and qRT-PCR analyses were performed to examine the expression pattern of sclerostin in young (20-30-year-old) and senescent (45-80-year-old) dental pulps. HDPCs were serially subcultured until senescence, and the expression of sclerostin was examined by qRT-PCR analysis. HDPCs with sclerostin overexpression and knockdown were constructed to investigate the role of sclerostin in HDPCs senescence and senescence-related impairment of odontoblastic differentiation potential. RESULTS: By immunohistochemistry and qRT-PCR, we found a significantly increased expression level of sclerostin in senescent human dental pulp compared with that of young human dental pulp. Additionally, elevated sclerostin expression was found in subculture-induced senescent HDPCs in vitro. By sclerostin overexpression and knockdown, we found that sclerostin promoted HDPCs senescence-related decline of proliferation and odontoblastic differentiation potential with increased expression of p16, p53 and p21 and downregulation of the Wnt signaling pathway. DISCUSSION: The increased expression of sclerostin is responsible for the decline of proliferation and odontoblastic differentiation potential of HDPCs during cellular senescence. Anti-sclerostin treatment may be beneficial for the maintenance of the proliferation and odontoblastic differentiation potentials of HDPCs.

Resolution of inflammation in periodontitis: a review.

Inflammation is a physiological response to an injury or infection. It is supposed to be self-limiting, stopping when the situation recovers to normal to protect the tissue. This self-limiting action is called "resolution of inflammation". Currently, periodontitis is thought to be the result of failed resolution of inflammation; specifically, it is the result of excessive inflammation that leads to gingival recession and alveolar bone loss. In this review, we will focus on the processes of resolution of inflammation in periodontitis, which may be a therapeutic target of periodontitis.