Transcriptional regulation mechanism of mineralization controlling factors, MEPE and DSPP

Mineralization is important process in the hard tissue including teeth and bone. Hypermineralization or hypomineralization causes malfunction, and then inhibits normal hard tissue formation. Matrix Extracellular PhosphoglycoprotEin (MEPE) and Dentin SialoPhosphoProtein (DSPP) are well known for potent factors in the bone and dentin mineralization, separately. They are members of Small Integrin Binding LIgand, N-linked Glycoprotein (SIBLING) family protein, which is composed of MEPE, DSPP, bone sialoprotein (BSP), osteopontin (OPN) and dentin matrix protein 1 (DMP1), and clustered on chromosome 4q21 in human and 5q in mouse, and have a similarity to produce Acidic-Serine-Asparate-Rich-MEPE-associated motif (ASARM). There are sufficient data supporting a role for MEPE protein function in mineralization, however, little is known about the regulation of MEPE gene expression. Therefore, we tried to find the transcriptional regulation mechanism of MEPE. Since MEPE expression is specifically expressed in the osteoblast, osteocyte, and BMPs, Wnts are well known by the importance in the bone formation, we could suppose the relationship in the MEPE expression through BMPs and Wnts. Mepe expression was increased by BMP-2 or Wnt3a treatment in the MC3T3-E1 cells, and conserved homeodomain (Dlx/Msx) response elements and LEF-1 binding elements were in the MEPE promoter region. First, in the part I, I demonstrated that MEPE expression is regulated by canonical BMP-2 signaling pathway through BMP R-Smads, Dlx5, Msx2 and Runx2 with Real time PCR, luciferase reporter assay with promoter deletion/mutant reporter vectors, EMSA and ChIP assay. Second, in the part II, I showed that MEPE expression is also regulated by canonical Wnt3a signaling pathway through -catenin/LEF1. Furthermore, I found that Wnt3a makes BMP-2 autocrine loop, and stimulates MEPE expression indirectly through BMP-2. Based on these MEPE gene transcriptional regulation mechanism, I tried to know more about MEPE function with PHEX in the bone formation and mineralization. In the part III, I demonstrated that DSPP expression is regulated by canonical BMP-2 signaling pathway in a same manner of the MEPE expression regulation by BMP-2. Transcriptional regulation mechanism had been identified through Runx2, CCAAT binding heterotrimeric transcription factor Y (NF-Y) and Twist1. Canonical BMP signaling pathway has been known to participate greatly in biomineralization, and DSPP expression is stimulated by BMP-2 treatment, however, previous studies overlooked the involvement of canonical BMP signaling pathway in the Dspp expression. Therefore, this study was designed to uncover this question, and I showed that DSPP expression is regulated by canonical BMP-2 signaling pathway. Collectively, I demonstrate here that BMP-2 and Wnt3a stimulate MEPE expression directly, and BMP-2 autocrine loop by Wnt3a also regulates MEPE expression indirectly in the MC3T3-E1 preosteoblastic cells. In addition to the MEPE transcriptional regulation mechanism, I suggest that MEPE/PHEX ratio is important to control bone formation and mineralization. Furthermore, I also proved that DSPP expression is canonical BMP-2 signaling pathway in the MDPC-23 preodontoblastic cells.Docto

Alveolar Ridge Preservation in the Severely Damaged Sockets of the Anterior Maxilla Followed by Delayed Implant Placement

We present the use of deproteinized bovine bone mineral and a non-crosslinked collagen membrane for the reconstruction of a significant alveolar bone defect in this clinical case report,. The patient had extensive alveolar bone loss in the anterior maxillary region, posing a challenge for implant placement. Therefore, alveolar ridge preservation was performed following tooth extraction, resulting in horizontal bone regeneration. Two implants were subsequently placed in the newly formed ridge, and radiographic evaluation demonstrated stable crestal bone levels following insertion of the final prosthesis.N

Dental Implant Placement in an Edentulous Maxilla with Chronic Rhinosinusitis: A Case Report

Implant surgery for an edentulous maxilla with severe resorption is challenging for clinicians, necessitating various preoperative considerations. This report demonstrates a case of implant placement for restoring an edentulous maxilla using guided bone regeneration and bilateral sinus lift surgery in a 47-year-old man with chronic rhinosinusitis. Prior to the surgical procedure, the patient had taken an antibiotic and a bronchodilator for 6 weeks after consulting with an otolaryngologist to minimize the risk of postoperative complications and implant failure. Seven implants were placed in the augmented maxillary anterior and posterior alveolar bones and were maintained without any complications. Meticulous preoperative evaluations increase the success rate of dental implantation, particularly in cases requiring invasive surgical procedures.N

Maxillary sinus pathology observed on CBCT requiring referral to an otolaryngologist before sinus floor elevation: A case report

Inverted papilloma is an uncommon sinus pathology usually affecting the maxillary sinus walls in its early stages. Although histologically benign, it has a relatively strong potential for local destruction, high recurrence rate, and the possibility of carcinomatous change. The current standard treatment is surgical removal by endoscopic sinus surgery. Since cone-beam computed tomography (CBCT) in dental clinics provides precise views of the maxillary sinus via high-resolution images, dentists can detect pathological alterations in the maxillary sinus, including inverted papilloma, and refer the patients to otolaryngologists in the early stage. This report documents a case of inverted papilloma detected on CBCT in the initial stage, which was treated by an otolaryngologist before implant placement. Finally, implant placement with osteotome sinus-floor elevation was safely performed after treating the neoplasm.N

Clinical evaluation of 3.0-mm narrow diameter implants: a retrospective study with up to 5 years of observation

Purpose: This study aimed to evaluate the clinical outcomes of a single type of narrow diameter implant (NDI) by investigating its survival rate and peri-implant marginal bone loss (MBL). In addition, variables possibly related to implant survival and MBL were investigated to identify potential risk factors. Methods: The study was conducted as a retrospective study involving 49 patients who had received 3.0-mm diameter TSIII implants (Osstem Implant Co.) at Seoul National University Dental Hospital. In total, 64 implants were included, and dental records and radiographic data were collected from 2017 to 2022. Kaplan-Meier survival curves and a Cox proportional hazard model were used to estimate the implant survival rate and to investigate the effects of age, sex, jaw, implant location, implant length, the stage of surgery, guided bone regeneration, type of implant placement, and the surgeons proficiency (resident or professor) on implant survival. The MBL of the NDIs was measured, and the factors influencing MBL were evaluated. Results: The mean observation period was 30.5 months (interquartile range, 26.75–45 months), and 6 out of 64 implants failed. The survival rate of the NDIs was 90.6%, and the multivariate Cox regression analysis showed that age was associated with implant failure (hazard ratio, 1.17; 95% confidence interval, 1.04–1.31, P=0.01). The mean MBL was 0.44±0.75 mm, and no factors showed statistically significant associations with greater MBL. Conclusions: NDIs can be considered a primary alternative when standard-diameter implants are unsuitable. However, further studies are required to confirm their long-term stability.N

Nicotinamide as a therapeutic agent for bone diseases

Nicotinamide (NAM), a water-soluble derivative of vitamin B3, has emerged as a potential therapeutic agent for bonerelated disorders. In particular, it promotes bone metabolism and alleviates delayed tooth eruptions associated with cleidocranial dysplasia (CCD). NAM serves as a precursor for nicotinamide adenine dinucleotide, a key coenzyme involved in cellular metabolism that plays an essential role in oxidative phosphorylation and mitochondrial function. Recent research has highlighted the capacity of NAM to enhance osteogenic differentiation and regulate the interaction between osteoblasts and osteoclasts, which is critical for maintaining bone homeostasis. Moreover, the effect of NAM in preventing delayed tooth eruptions in CCD models underscores its potential as a noninvasive therapeutic option. Considering its safety profile and therapeutic potential, NAM is a promising candidate for longterm treatment of bone diseases and prevention of age-related bone disorders.N

Effects of adjacent periodontitis on osseointegrated dental implants

Purpose: This study aimed to investigate whether new-onset periodontitis or apical periodontitis in the adjacent teeth affects osseointegrated dental implants in a beagle dog model. Methods: One control group and 2 experimental groups (periodontitis and apical periodontitis groups) were defined based on the presence of experimental periodontitis or apical periodontitis, with 1 beagle dog randomly assigned to each group. The mandibular second and fourth premolars on both sides of the 3 beagles were extracted. Eight weeks after extraction, 4 bone-level implant fixtures, 2 on both sides of each mandible, were placed in each beagle. Six weeks after implant surgery, healing abutments were connected. After sufficient osseointegration, plaque control was performed in the control group, while periodontitis and apical periodontitis were induced in the experimental groups. The beagles were euthanized for histological analyses 20 weeks after induction of experimental periodontitis. Statistical analyses were performed using the Kruskal–Wallis test with the Bonferroni correction to compare the 3 groups. Results: The implants in the control and apical periodontitis groups were well-maintained, while those in the periodontitis group showed clinical signs of inflammation with bone resorption. The bone-to-implant contact (BIC) and bone area values in the periodontitis group were lower than those in the other groups. The distance between the implant shoulder and the first BIC was significantly greater in the periodontitis group than in the control group (P<0.05). Conclusions: The presence of periodontitis in adjacent teeth can pose a risk to dental implants, potentially resulting in peri-implantitis. However, this was not observed for apical periodontitis. Within the limitations of this study, periodontal care is necessary to reduce the impact of periodontitis in adjacent teeth on osseointegrated implants.N

The cumulative survival rate of dental implants with micro-threads: a long-term retrospective study

Purpose: This study aimed to evaluate the long-term cumulative survival rate (CSR) of dental implants with micro-threads in the neck over a 10-year follow-up period and to examine the factors influencing the survival rate of dental implants. Methods: This retrospective study was based on radiographic and dental records. In total, 151 patients received 490 Oneplant® dental implants with an implant neck micro-thread design during 2006–2010 in the Department of Periodontology of Seoul National University Dental Hospital. Implant survival was evaluated using Kaplan–Meier analysis. Cox proportional hazard regression analysis was used to identify the factors influencing implant failure. Results: Ten out of 490 implants (2.04%) failed due to fixture fracture. The CSR of the implants was 97.9%, and no significant difference was observed in the CSR between external and internal-implant types (98.2% and 97.6%, respectively, P=0.670). In Cox regression analysis, 2-stage surgery significantly increased the risk of implant failure (hazard ratio: 4.769, P=0.039). There were no significant differences in influencing factors, including sex, age, implant diameter, length, fixture type, location, surgical procedure, bone grafting, and restoration type. Conclusions: Within the limitations of this retrospective study, the micro-thread design of the implant neck was found to be favorable for implant survival, with stable clinical outcomes.N