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Osteoblasts participate in both bone formation through the synthesis of extracellular matrix and osteoclast differentiation through the expression of osteoclast differentiation factor. Osteoblasts communicate with each other via gap junctions (GJ), which enable small molecules, such as cAMP, to move to adjacent cells. Therefore, we focused on the role of cAMP propagation between osteoblasts via GJ in the osteoclast-supporting activity of osteoblasts. Osteoclast-supporting activity was evaluated by a co-culture system of osteoblasts with bone marrow-derived mononuclear cells. In this system, ablation of Gja1, a gene encoding connexin 43, in osteoblasts promoted osteoclastogenesis induced by prostaglandin E

In guided bone regeneration (GBR), a barrier membrane is applied to provide a space for bone regeneration to promote cell adhesion, cell proliferation, and bone regeneration by inducing cell migration to the surface of the bone-deficient site. We prepared a non-woven absorbable membrane for GBR comprised of a copolymer of L-lactic acid and glycolic acid (PLLGA) using the dry spinning method. A thin and dense membrane comprising unsintered hydroxyapatite (uHA) and poly-L-lactic acid (PLLA) was used for comparison. Osteoblast TMS-12 cells were seeded onto the membranes, and cell adhesion and proliferation rates were examined. Calcification levels were quantified by Alizarin Red S staining after cell culture in calcification induction medium. Osteoblastic gene expression was examined by RT-PCR. Cell adhesion and proliferation rates and calcification on PLLGA membranes were significantly higher than those on uHA/PLLA membranes. PLLGA membranes upregulated osteogenic gene expression compared to on uHA/PLLA membranes. Non-woven PLLGA membranes may be useful in GBR for promoting bone formation and maturation.

Background During implant treatment in the maxillary molar area, maxillary sinus floor augmentation is often performed to ameliorate the reduced alveolar bone height attributable to bone remodeling and pneumatization-induced expansion of the maxillary sinus. However, this augmentation may cause complications such as misplaced implants, artery damage, and maxillary sinus mucosal perforation; infections like maxillary sinusitis; and postsurgical complications such as bone graft leakage and postoperative nasal hemorrhaging. To reduce the complications during maxillary sinus floor augmentation and postoperative infections, we performed retrospective investigations of various systemic and local factors that influence pre-operative sinus mucosal thickness (SMT) by using cone-beam computed tomography (CBCT). Subjects included patients who underwent maxillary sinus floor augmentation in an edentulous maxillary molar area with a lateral approach. Pre-operative SMT, existing bone mass, and nasal septum deviation were measured using CBCT images. Relationships between SMT and the following influencing factors were investigated: (1) age, (2) sex, (3) systemic disease, (4) smoking, (5) period after tooth extraction, (6) reason for tooth extraction, (7) residual alveolar bone height (RBH), (8) sinus septa, and (9) nasal septum deviation. Correlations were also investigated for age and RBH (p < 0.05). Results We assessed 35 patients (40 sinuses; 11 male, 24 female). The average patient age was 58.90 ± 9.0 years (males, 57.9 ± 7.7 years; females, 59.9 ± 9.4 years; age range, 41–79 years). The average SMT was 1.09 ± 1.30 mm, incidence of SMT > 2 mm was 25.0%, incidence of SMT < 0.8 mm was 50.0%, and the average RBH was 2.14 ± 1.02 mm. The factors that influenced SMT included sex (p = 0.0078), period after tooth extraction (p = 0.0075), reason for tooth extraction (p = 0.020), sinus septa (p = 0.0076), and nasal septum deviation (p = 0.038). Conclusions Factors associated with higher SMT included male sex, interval following tooth extraction < 6 months, periapical lesions, sinus septa, and nasal septum deviation. Factors associated with SMT > 2 mm were sex and reason for tooth extraction, while factors associated with SMT < 0.8 mm were time following tooth extraction and nasal septum deviation. Despite the limitations of this study, these preoperative evaluations may be of utmost importance for safely conducting maxillary sinus floor augmentation.

Background We performed maxillary sinus floor augmentation using the crestal approach and beta-tricalcium phosphate (β-TCP) and a long-term evaluation using cone-beam computed tomography (CBCT). Methods Twenty-three patients (30 implants) underwent sinus floor augmentation using the osteotome technique. Subjects underwent CBCT imaging before surgery, immediately after surgery, and at follow-up (≥ 3 years after surgery). We measured the changes in height of the augmented sinus floor (SL), the augmented bone above apex of the implant (BH), and the implant length that projected into the sinus (IL). Results The mean SL decreased from 6.54 ± 1.51 (immediately after surgery) to 3.11 ± 1.35 mm (follow-up). The mean BH decreased from 3.17 ± 0.97 to − 0.25 ± 1.19 mm; the maxillary sinus floor in many implants was near the apex at follow-up. The SL at follow-up showed a strong correlation with the IL (p = 0.0057). Conclusions Osteotome sinus floor elevation with beta-tricalcium phosphate was clinically effective. Cone-beam computed tomography analysis revealed that ≥ 3 years after surgery, the maxillary sinus floor was near the apex of the implant.

Osteopontin (OPN) is not only a marker of osteoblasts but it is also related to cancer progression and inflammation. The expression of OPN increases in response to inflammatory cytokines, hormones, and mechanical stress. Among them, cyclic-AMP (cAMP) elevating agents stimulate OPN expression in the presence of 1, 25-OH vitamin D3 (VD3). We aimed to clarify the mechanism by which cAMP enhances OPN expression in osteoblastic cells. The OPN promoter (-2335 to +76, OPNp2335) exerted a cell type specific response to forskolin (FK) and VD3. Sequential deletion analysis of OPNp revealed that the OPNp (-833 to +76) contained essential responsive regions to respond to cAMP signaling. In particular, both Vitamin D response element (VDRE, -758 to -743) and osteoblast-specific cis- acting element 2 (OSE2, -695 to -690) were essential for cAMP-mediated OPNp activity. The expression of vitamin D receptor (VDR), but not runt-related transcription factor 2 (Runx2), a nuclear receptor for OSE2, was induced by the treatment of the cells with FK. Although, VD3-induced OPNp activity was slightly enhanced in VDR-overexpressing osteoblasts, it reached the same level as that of osteoblasts induced by both VD3 and FK in the presence of histone deacetylase (HDAC) inhibitor. Moreover, we identified histone acetylation on the OPN promoter region by FK treatment. These results strongly suggest that OPNp activity is controlled by the cAMP signaling via genetic and epigenetic regulations.

The effectiveness of a previously developed unsintered hydroxyapatite (uHA) and poly(L-lactic acid) (PLLA) hydrophilic membrane as a resorbable barrier for guided bone regeneration (GBR) was evaluated. Critical-size 8-mm diameter bone defects were surgically generated in the parietal bones of 24 12-week-old male Wistar rats, which were then divided into three groups in which either a uHA/PLLA or a collagen membrane or no membrane (control) was placed onto the bone defect. Following sacrifice of the animals 2 or 4 weeks after surgery, bone defects were examined using microcomputed tomography and histological analysis. Bone mineral density, bone mineral content, and relative bone growth area values 2 or 4 weeks after surgery were highest in the uHA/PLLA group. Four weeks after surgery, the relative bone growth area in the uHA/PLLA group was larger than that in the collagen group. The resorbable uHA/PLLA membrane is thus potentially effective for GBR.

The aim of this study was to evaluate clinical outcomes of staged sinus floor elevation (SFE) using novel low-crystalline carbonate apatite (CO3Ap) granules. Patients who needed SFE for implant placement were recruited into this clinical trial. A staged procedure (lateral window technique using CO3Ap granules, followed by implant placement after 7 ± 2 months) was employed in 13 patients. Bone-height increase and insertion torque values (ITVs) were assessed along with histological evaluation. The survival and success rates of 3-year functioning implants were also evaluated. Mean of bone-height increase after SFE using CO3Ap granules was 7.2 ± 2.5 mm and this increase allowed implant placement in all cases (17 implants). Mean of ITV was 25.1 ± 13.2 Ncm and primary stability was achieved successfully in all cases. Histological analyses revealed mature new bone formation (36.8 ± 17.3%) and residual CO3Ap granules (16.2 ± 10.1%) in the compartment after SFE. The survival and success rates after 3-year functional loading were 100% and no complications were found. These results clearly indicate the clinical usefulness of CO3Ap granules for SFE.

Purpose The purpose of this study was to elucidate the efficacy and safety of carbonate apatite (CO3Ap) granules in 2-stage sinus floor augmentation through the radiographic and histomorphometric assessment of bone biopsy specimens. Methods Two-stage sinus floor augmentation was performed on 13 patients with a total of 17 implants. Radiographic assessment using panoramic radiographs was performed immediately after augmentation and was also performed 2 additional times, at 7±2 months and 18±2 months post-augmentation, respectively. Bone biopsy specimens taken from planned implant placement sites underwent micro-computed tomography, after which histological sections were prepared. Results Postoperative healing of the sinus floor augmentation was uneventful in all cases. The mean preoperative residual bone height was 3.5±1.3 mm, and this was increased to 13.3±1.7 mm by augmentation with the CO3Ap granules. The mean height of the augmented site had decreased to 10.7±1.9 mm by 7±2 months after augmentation; however, implants with lengths in the range of 6.5 to 11.5 mm could still be placed. The mean height of the augmented site had decreased to 9.6±1.4 mm by 18±2 months post-augmentation. No implant failure or complications were observed. Few inflammatory cells or foreign body giant cells were observed in the bone biopsy specimens. Although there were individual differences in the amount of new bone detected, new bone was observed to be in direct contact with the CO3Ap granules in all cases, without an intermediate layer of fibrous tissue. The amounts of bone and residual CO3Ap were 33.8%±15.1% and 15.3%±11.9%, respectively. Conclusions In this first demonstration, low-crystalline CO3Ap granules showed excellent biocompatibility, and bone biopsy showed them to be replaced with bone in humans. CO3Ap granules are a useful and safe bone substitute for two-stage sinus floor augmentation. Trial Registration ICTRP Identifier: JPRN-UMIN000019281, Graphical Abstract

The trigger for bone remodeling is bone resorption by osteoclasts. Osteoclast differentiation only occurs on the old bone, which needs to be repaired under physiological conditions. However, uncontrolled bone resorption is often observed in pro-inflammatory bone diseases, such as rheumatoid arthritis. Mature osteoclasts are multinuclear cells that differentiate from monocyte/macrophage lineage cells by cell fusion. Although Osteoclast precursors should migrate across osteoblast layer to reach bone matrix before maturation, the underlying mechanisms have not yet been elucidated in detail. We herein found that osteoclast precursors utilize two routes to migrate across osteoblast layer by confocal- and electro-microscopic observations. The osteoclast supporting activity of osteoblasts inversely correlated with osteoblast density and was positively related to the number of osteoclast precursors under the osteoblast layer. Osteoclast differentiation was induced by IL-1s, but not by PGE2 in high-density osteoblasts. Osteoblasts and osteoclast precursors expressed CX3CL1 and CX3CR1, respectively, and the expression of CX3CL1 increased in response to interleukin-1s. An anti-CX3CL1-neutralizing antibody inhibited the migration of osteoclast precursors and osteoclast differentiation. These results strongly suggest the involvement of CX3CL1 in the migration of osteoclast precursors and osteoclastogenesis, and will contribute to the development of new therapies for bone diseases. J. Cell. Physiol. 232: 1739-1745, 2017. © 2016 Wiley Periodicals, Inc.

Background Previous studies have shown that porous composite blocks containing uncalcined hydroxyapatite (u-HA; 70 wt%) with a scaffold of poly-DL-lactide (PDLLA, 30 wt%) are biodegradable, encourage appropriate bone formation, and are suitable for use as a bone substitute in vertical ridge augmentation. The present study aimed to accelerate osteogenesis in vertical ridge formation by adding types 1 and 3 collagen to the u-HA/PDLLA blocks and assessing the effect. Material and methods The bone substitute in the present study comprised porous composite blocks of u-HA (70 wt%) with a PDLLA (27–29 wt%) scaffold and enriched with types 1 and 3 collagen (1.7 ~ 3.4 wt%). The control blocks were composed of u-HA (70 wt%) and PDLLA (30 wt%). The materials were formed into 8-mm diameter, 2-mm high discs and implanted onto the cranial bones of six rabbits. The animals were sacrificed 4 weeks after implantation, and histological and histomorphometrical analyses were performed to quantitatively evaluate newly formed bone. Results New bone formation occurred with both block types, showing direct contact with the original bone. Mean ± standard deviation bone formation was significantly greater in the experimental blocks (25.6% ± 4.8%) than in the control blocks (17.0% ± 4.7%). Conclusions Histological and histomorphometrical observations indicated that new bone was formed with both block types. The u-HA/PDLLA block with types 1 and 3 collagen is a more promising candidate for vertical ridge augmentation than the u-HA/PDLLA alone block.

Purpose Carbonate apatite (CO3Ap), an inorganic component of human bone, can be fabricated in chemically pure form from calcium carbonate block via a dissolution-precipitation reaction. A first-in-human clinical trial was conducted in which low-crystalline CO3Ap granules were evaluated for safety and efficacy in sinus floor augmentation and simultaneous implant installation. Materials and Methods Procedures were performed in 8 patients (9 implants) with 2 granule sizes: small (300 to 600 μm) and medium (600 to 1,000 μm). Panoramic radiographic assessment was performed immediately after augmentation, 7 ± 2 months after augmentation, 6 ± 2 months after prosthetic loading, and 12 ± 2 months after prosthetic loading. Results Postoperative healing was uniformly uneventful, with no abnormal bleeding, pain, or swelling, and all implants achieved successful osseointegration. The mean residual maxillary molar bone height was 5.2 ± 0.8 mm preoperatively and increased to 14.0 ± 1.9 mm after augmentation. Implants 9.0 to 11.5 mm in length were placed. The post-augmentation height decreased to 12.4 ± 1.3 mm at 7 ± 2 months; after prosthetic loading, it decreased to 11.9 ± 0.8 mm at 6 ± 2 months and 11.7 ± 0.6 mm at 12 ± 2 months. No abnormal bone resorption of the augmented areas was observed, and bone height supporting the implants was maintained. The overall implant survival rate was 100%, with no implant failures or complications during the first year. Conclusions Low-crystalline CO3Ap granules were useful and safe for sinus floor augmentation and simultaneous implant installation, providing a promising bone substitute for dental implant surgery.

Objectives The objective of this study was to examine peri-implant mucosal thickness at different sites of peri-implant crevice around 70 implants placed in 35 patients. Material and methods The peri-implant mucosal thickness was defined as distance of the peri-implant mucosal margin and the coronal edge of bone/implant contact and measured using the cast models and dental radiography. Results The overall mean peri-implant mucosal thickness was 3.6 ± 1.4 mm, wherein maxillary anterior implants, maxillary posterior implants and mandibular posterior implants had significantly different dimensions of median thickness of 4.25, 3.75 and 3.0 mm, respectively. Furthermore, the mesial and distal sites of those positioned implants measured unevenness in the thickness especially in the maxillary posterior region with statistical significance. Conclusion The proposed methodology to evaluate peri-implant mucosal thickness measured with a big variation from overall 3.6 mm with a big variation from 1.6 to 7.0 mm in healthy volunteers. And significant difference was found in the depth among the three regions and, statistically, dispersion of individual peri-implant mucosal thickness resulted in lack of consistency. Although dental implants have been well developed, predictable and prevailing prosthetics, onset of peri-implantitis might be inevitable in some cases. Therefore, establishment of a standardized dimensional diagnosis of peri-implant tissues followed by pathologic ascertainment could be taken into account for the prevention or curing of peri-implantitis.

Purpose: This study investigated the attitude of patients, grouped by the Brinkman index, towards smoking by using the Kano Test for Social Nicotine Dependence (KTSND) and their knowledge of peri-implantitis. Methods: The participants were 3093 new patients who visited the Tokyo Medical and Dental University Hospital from January 2012 to December 2013 for an oral implant. The methodology included a questionnaire about sex, age, smoking status, daily average number of cigarettes, years of smoking, knowledge of peri-implantitis, and the KTSND. The patients were grouped according to their smoking status by calculating their Brinkman index (over 200 or not): current smokers with the possibility of nicotine dependence (BI(+)CS), current smokers with no possibility of nicotine dependence (BI(-)CS), ex-smokers (ES), and non-smokers (NS). The Brinkman index is obtained by multiplying one’s daily average number of cigarettes by the number of years they have been smoking. Results: Data were collected from 2182 respondents (response rate = 71%). The KTSND scores of BI(+)CS (16.89 ± 4.26) were significantly higher than the scores of ES (11.99 ± 4.52) and NS (11.53 ± 5.01). In current smokers, there were no significant differences between BI(+)CS and BI(-)CS. The patients replied “I don’t know” about peri-implantitis most often in all groups; however, there were no significant differences between the groups. Discussion: BI(+)CS were more dependent on nicotine in social situations than the other groups were. In Japan, a Brinkman index over 200 is required for a nicotine-dependence management fee to be instituted for health insurance treatment. This is a major concern for young smokers, who may be excluded from treatment because their years of smoking are substantially less. Results revealed that there were no significant differences between BI(+)CS and BI(-)CS. Therefore, it was suggested that the Brinkman index did not sufficiently group the participants.

A 47-year-old man underwent surgical resection and reconstruction with a fibula osteocutaneous flap. After the surgery, a surgical obturator was placed and adjusted. After flap healing, a conventional obturator was fabricated with polymethyl methacrylate resin and retained by the anatomical undercuts around the reconstructed fibula bone flap and the posterior part of the defect. As the defect shape changed with time, a second conventional obturator was fabricated and fitted. No further recurrence of myoepithelioma was observed for 2 years, and the patient was satisfied with the obturator during mastication and speech; however, despite having no major complaints, the patient found it difficult to chew on the right side, and the obturator was displaced slightly downward when the mouth was opened wide and shifted when chewing hard and sticky food. Thus, an implant-retained obturator was suggested to provide better retention and stability. Four dental implants were therefore placed into the fibula bone, although one did not osseointegrate because either primary stability was insufficient or overload was affected in the nonloaded implant environment and was replaced. After fitting custom abutments with a magnet, an implant-retained obturator was placed, and the patient was satisfied with the outcome. During 3 years of follow-up, no issues were noted with the implant bodies, abutments, obturator, or reconstructed site. The conventional obturator was displaced slightly downward when the patient opened his mouth wide, and it shifted when chewing hard and sticky food because there was limited fibula bone at the reconstruction site and more available posteriorly. For better retention and stability, the implant-retained obturator was fabricated with a custom abutment and magnetic retention. The patient was satisfied with the results, as improved implant retention increased the stability of the prosthesis. This clinical report describes the rehabilitation of a bilateral maxillectomy patient with a free fibula osteocutaneous flap and an implant-retained obturator. The patient's oral functions were improved when the prosthesis was stabilized by means of dental implants and custom abutments.

Background When augmenting the maxillary sinus without grafting material, the method used to cover the bony window is a subject of debate. Purpose The purpose of this study was to evaluate the poly-L-lactic acid (PLLA) membrane as closing material of the lateral window in a maxillary sinus augmentation without bone grafting. Materials and Methods Augmentation of the maxillary sinus without grafting material and installation of titanium screws that fix the Schneiderian membrane were performed in 18 Japanese male white rabbits. The bony window was covered with a collagen membrane or PLLA membrane or no membrane. The animals were sacrificed at 4 or 8 weeks. New bone volume was calculated radiologically using microcomputed tomography (micro-CT). The samples were analyzed histologically after toluidine blue staining. Results No significant differences were observed in the new bone volume, as measured by micro-CT. However, histomorphometric analysis demonstrated the superiority of the PLLA membrane in new bone formation compared with the collagen membrane. Conclusion The PLLA membrane is a suitable material to be applied for tissue regeneration in this animal model.

Background Recently, the occurrence of peri-implantitis has been increasing. However, a suitable method to debride the contaminated surface of titanium implants has not been established. The aim of this study was to investigate the morphologic changes of the microstructured fixture surface after erbium laser irradiation, and to clarify the effects of the erbium lasers when used to remove calcified deposits from implant fixture surfaces. Methods In experiment 1, sandblasted, large grit, acid etched surface implants were treated with Er:YAG laser or Er,Cr:YSGG laser at 30 to 60 mJ/pulse and 20 Hz with water spray. In experiments 2 and 3, the effects of erbium lasers used to remove calcified deposits (artificially prepared deposits on virgin implants and natural calculus on failed implants) were investigated and compared with mechanical debridement using either a titanium curette or cotton pellets. After the various debridement methods, all specimens were analyzed by stereomicroscopy (SM), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS). Results Stereomicroscopy and SEM showed that erbium lasers with optimal irradiation parameters did not influence titanium microstructures. Compared with mechanical debridement, erbium lasers were more capable of removing calcified deposits on the microstructured surface without surface alteration using a noncontact sweeping irradiation at 40 mJ/pulse (ED 14.2 J/cm2 /pulse) and 20 Hz with water spray. Conclusion These results indicate that Er:YAG and Er,Cr:YSGG lasers are more advantageous in removing calcified deposits on the microstructured surface of titanium implants without inducing damage, compared to mechanical therapy by cotton pellet or titanium curette.

Introduction We have recently used highly pure β-TCP (beta-tricalcium phosphate) as the bone grafting material to avoid highly invasive autogenous bone grafting. We evaluated the osseoconduction potential of highly pure β-TCP in sinus augmentation surgery treatment. Materials and methods The study group comprised 13 patients who underwent maxillary sinus floor augmentation with β-TCP alone. Seven patients underwent sinus augmentation and implant placement simultaneously. Six patients were treated with a staged approach. Six months after surgery, specimens were obtained from 7 patients (for lateral biopsy) and 6 patients (for vertical biopsy). Results Histological and histomorphometrical analysis showed a mean bone proportion of 30.8% (vertical) and 12.0% (lateral) for new bone formation and good integration of the β-TCP. New bone formation was lower in the lateral biopsy specimens than in the vertical. Conclusion Highly pure β-TCP is a safe bone-grafting material with superior osteoconductive properties. Histologic and radiographic examinations indicate that β-TCP is slowly resorbed, which results in unresorbed graft material remaining even 6 months after the procedure, and that new bone replacement occurs slowly for approximately 1 year.

Fibroblast growth factor (FGF) signaling is involved in skeletal development. Among total 22 FGFs, it is suggested that FGF18 functions in promotion of osteoblast differentiation. In order to elucidate the mechanism of FGF18-dependent acceleration of osteogenesis, we implanted rhFGF18 soaked beads over mouse fetal coronal sutures using ex-utero surgery. The coronal suture area comprises the peripheries of the developing frontal and parietal bones, separated by the sutural mesenchyme. rhFGF18 accelerated osteogenesis by promoting connection of the frontal and parietal bone domains, resulting in elimination of the sutural mesenchyme. Expression of Fgf receptors, Fgfr1, -2 and -3 involved in skeletal development, was maintained or upregulated in the developing bone domains, consistent with enhanced osteogenesis. Bone morphogenetic protein (Bmp) 2 was specifically upregulated in the skeletogenic layer and the application of Bmp antagonist, rmNoggin, inhibited rhFGF18-dependent upregulation of osteoblast markers. These results suggest that FGF18 accelerates osteogenesis by upregulation of Bmp2 as well as maintenance or upregulation of Fgfr1, -2 and -3 expression in osteoblasts.

Objective This aim of this study was to investigate the differences between patients with and without a treatment history of dental implants by use of a questionnaire survey in order to determine the information that is required for patients undergoing dental implants. Materials and Methods The questionnaires were given to 4512 patients who visited the Tokyo Medical and Dental University Hospital for oral implants between January 2012 and December 2014, and 2972 (66%) valid questionnaires were collected. Results There were 857 patients with a treatment history of dental implants and 2115 patients without. “Preservation of an adjacent tooth” was the reason that 32% of these patients chose implant therapy, and the patients without treatment history were significantly higher than the patients with one. Significantly, more patients without a treatment history of dental implants selected the after-effects of surgery and pain after surgery as their main concerns for implant therapy compared to those with a treatment history. In the question “Pain after surgery,” the patients without treatment history did not know significantly lower than the patients with one. Conclusions Patients without a treatment history of dental implants placed more importance on the preservation of healthy teeth. Because patients, in particular those without a treatment history of dental implants, are anxious about surgery, we should provide them with more information on treatment than we already do and explain the risks of treatment to them. To keep the credence between doctors and patients, informed consent and patient education on treatment are six important concerns.

The trigger for bone remodeling is bone resorption by osteoclasts. Osteoclast differentiation only occurs on the old bone, which needs to be repaired under physiological conditions. However, uncontrolled bone resorption is often observed in pro-inflammatory bone diseases, such as rheumatoid arthritis. Mature osteoclasts are multinuclear cells that differentiate from monocyte/macrophage lineage cells by cell fusion. Although Osteoclast precursors should migrate across osteoblast layer to reach bone matrix before maturation, the underlying mechanisms have not yet been elucidated in detail. We herein found that osteoclast precursors utilize two routes to migrate across osteoblast layer by confocal- and electro-microscopic observations. The osteoclast supporting activity of osteoblasts inversely correlated with osteoblast density and was positively related to the number of osteoclast precursors under the osteoblast layer. Osteoclast differentiation was induced by IL-1ß, but not by PGE

Background It is important to visualize the phenomenon which occurs in actual clinical cases to decide the timing of implant placement subsequently after sinus graft. Although several clinical cases of bone augmentation using xenograft have been evaluated, the number of those reports which have described bone remodeling by alloplasty are not sufficient. Findings In the present report, to investigate bone remodeling histologically after maxillary sinus augmentation with porous hydroxyapatite alloplast, bone cores from the sinus floor of three female nonsmoking patients (aged 64–73 years) were collected 6 months after sinus lift surgery, embedded in methyl methacrylate resin, and prepared by conventional methods. Bone architecture and graft residues were evaluated by micro-computed tomography of the same specimens. Hematoxylin–eosin and Villanueva–Goldner staining revealed mature osteoblasts and multinucleated osteoclasts on the grafted sinus floor and surface of residual hydroxyapatite particles. The particulate interspace was partially filled with osteoid and calcified tissue and showed active vascularization. Conclusion The results suggested that bone regeneration and angiogenesis within and between porous hydroxyapatite particles were sufficiently found after 6 month histologically in the grafted sinus floor. Electronic supplementary material The online version of this article (doi:10.1186/s40064-016-1885-2) contains supplementary material, which is available to authorized users.

Maxillary sinus floor elevation using autologous or alloplastic bone grafting is often performed for implant treatment of maxillary molars; however, issues related to the donor site and complications such as infection have been reported. We performed maxillary sinus floor elevation using poly-L-lactic acid (PLLA) as a space-making material in patients with an insufficient bone mass (

Background The long-term stability of maxillary sinus floor augmentation with β-TCP remains largely unknown. We report the long-term assessment of volumetric changes in maxillary sinus floor augmentation with β-TCP by cone-beam computed tomography (CBCT). Methods The subjects included 30 patients who underwent maxillary sinus floor augmentation using β-TCP and 58 implant placement for unilateral maxillary defect, simultaneously. Volumetric changes in β-TCP and the height of peri-implant bone were analyzed by CBCT. Results In all patients, the mean volume of the grafted bone decreased from immediately after implant placement to 6 months after implant placement (75.6 % reduction rate); it decreased further at 2.5 years after implant placement (54.9 % reduction rate). The mean of the height from the implant tip to the maxillary sinus floor was 2.00 ± 1.51 mm, 0.73 ± 1.33 mm, and −0.72 ± 1.11 mm immediately, 6 months, and 2.5 years after implant placement, respectively. The implant tip protruded beyond the maxillary sinus floor in approximately 70 % of the implants (41/58 implants) at 2.5 years after surgery. During the observation period, the implant survival rate was 100 %. Conclusions The radiographic analysis by CBCT is considerably more advanced than previous radiographic examinations. Although maxillary sinus pneumatization continues to progress ≥1 year after maxillary sinus floor augmentation with β-TCP, it stabilizes 3 years after surgery.

The clinical analysis of 462 patients (154 men and 308 women) with problems of implant therapy done at other clinics is reported. They visited the clinic for oral implant of the Tokyo Medical and Dental University Hospital during the period from January 1996 to March 2002. The results were as follows: 1) The majority of the patients (76.6%) were 40 to 69 years of age. 2) Of the total patients, 26.8% had been referred from the other outpatient clinics in our hospital, 14.7% from private dental offices and 2.6% from attending doctors. 3) There were 361 patients with complications related to the implant therapy. Seventy-six patients asked for second opinions concerned about a diagnosis or treatment recommendation. Thirty patients required maintenance of the implants. 4) The most common complications observed were peri-implantitis (184 cases). Prosthodontic complications (72 cases) included framework/resin/veneering material fractures, screw loosening and fractures. There were implant fractures in 21 cases, sensory disturbance in 20 cases, problems related to sinus in 13 cases, problems of connected teeth in 30 cases and phonetic/esthetic complications in 10 cases. 5) The types of problem implants were osseointegrated implants (196 cases), alumina-ceramic implants (74 cases), metallic blade-type implants (35 cases), pin-type implants (10 cases), subperiosteal implants (6 cases) and other implants.

A 47-year-old man underwent surgical resection and reconstruction with a fibula osteocutaneous flap. After the surgery, a surgical obturator was placed and adjusted. After flap healing, a conventional obturator was fabricated with polymethyl methacrylate resin and retained by the anatomical undercuts around the reconstructed fibula bone flap and the posterior part of the defect. As the defect shape changed with time, a second conventional obturator was fabricated and fitted. No further recurrence of myoepithelioma was observed for 2 years, and the patient was satisfied with the obturator during mastication and speech; however, despite having no major complaints, the patient found it difficult to chew on the right side, and the obturator was displaced slightly downward when the mouth was opened wide and shifted when chewing hard and sticky food. Thus, an implant-retained obturator was suggested to provide better retention and stability. Four dental implants were therefore placed into the fibula bone, although one did not osseointegrate because either primary stability was insufficient or overload was affected in the nonloaded implant environment and was replaced. After fitting custom abutments with a magnet, an implant-retained obturator was placed, and the patient was satisfied with the outcome. During 3 years of follow-up, no issues were noted with the implant bodies, abutments, obturator, or reconstructed site. The conventional obturator was displaced slightly downward when the patient opened his mouth wide, and it shifted when chewing hard and sticky food because there was limited fibula bone at the reconstruction site and more available posteriorly. For better retention and stability, the implant-retained obturator was fabricated with a custom abutment and magnetic retention. The patient was satisfied with the results, as improved implant retention increased the stability of the prosthesis. This clinical report describes the rehabilitation of a bilateral maxillectomy patient with a free fibula osteocutaneous flap and an implant-retained obturator. The patient's oral functions were improved when the prosthesis was stabilized by means of dental implants and custom abutments.

Bone morphogenetic proteins have been found to be one of the most promising osteoinductive substances and they are expected to be utilized clinically for the reconstruction of defective mandibles. However, newly formed bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) has not yet been proven able to withstand the masticatory force applied by oral implants. In this study, we examined the qualitative changes in an rhBMP-2-induced mandible from the functional force of osseointegrated oral implants. Segmental (30 mm) bone defects were created in the mandibles of beagles. A poly D,L-lactic coglycolic acid-coated gelatin sponge impregnated with rhBMP-2 was grafted to the resected canine mandible. The new bone was formed 8 weeks after surgery and the Branemark system fixtures were implanted into the reconstructed mandible. After another 8 weeks, the prosthesis was placed over the oral implants. The prosthesis was maintained in occlusion with the opposing natural dentition for 0, 4, 12, 24, or 48 weeks before the animal was euthanized. The quality of regenerated bone was then evaluated histologically and the osseointegration ratio between oral implants and the bonemeasured. During the first 4 weeks, the ratio remarkably increased from 48.9% to 64.5%. After 48 weeks, the ratio approached about 74.5%. The bone loaded for 48 weeks had undergone extensive remodeling and consolidation; its quality was better and maturer than that of bone that was not loaded. These results indicated that the newly formed bone induced by rhBMP-2 was able to withstand the masticatory force applied by oral implants and had become as functionally mature as a natural bone.

The purpose of this study was to investigate new patients who had already received treatment with dental implants. The subjects were patients who visited the clinic for oral implants at Tokyo Medical and Dental University Hospital from April 1995 to March 2012. The results were as follows: 1) Of the total number of patients, there were 2,419 patients (14.0%) with dental implants. 2) Of the 2,419 patients, 252 patients (10.4%) had been referred from operating doctors or operating clinics. 3) There were 1,516 (62.7%) patients with complaints related to the implant therapy. 4) There were 1,367 (56.5%) patients who had ill feelings toward their attending doctors. 5) There were 1,112 (46.0%) patients with biological complications. 6) Regarding patients with or without a referral from the doctor who had performed their dental implant, those patients who had been referred showed significantly higher occurrence of loss of implants, neurological symptoms, doctor's recommendation, prosthetic problems, and surgical problems. Almost implant therapies were treated with other treatments for natural teeth, including surgical treatment, prosthetic treatment, periodontal treatment and maintenance. These were too complex to enable the results to be forecast before treatment, therefore unpredictable symptoms often occur in patients with implant therapy. Informed consent including patient education is important, but the results of this study suggest that it is insufficient at present.

Abstract An alveolar cleft often displays the furrowed shape of the buccal site because of the lack of alveolar bone and gingival contracts. A 35-year-old woman presented with a repaired cleft lip and a non-grafted alveolar cleft associated with a missing lateral incisor on the left side of the maxilla. The central incisor had been an abutment tooth of a bridge for 15 years; however, it fractured and was extracted. Orthodontic treatment was antecedent to implant reconstruction because the edentulous space was not adequate for a single tooth replacement. As the palate was closed by the mucosa, bone grafting was not performed at the cleft site beforehand. Dental implant placement was performed within the narrowed, beamlike bone, and hydroxyapatite particles were used to augment the ridge. A relaxing incision and expansion of the invaginated mucosa improved the buccal shape of the gum. The usage of a narrow-type implant and bone substitutes facilitated the minimization of surgical stress, even though she did not undergo autologous bone-grafting surgery. Additionally, the aesthetical reconstruction of the anterior region significantly improved her quality of life at the 3-year follow-up.

A retrospective study was made on 1,000 outpatients visiting the Clinic for Oral Implant, University Hospital, Faculty of Dentistry, Tokyo Medical and Dental University between April 1995 and June 1998. The following findings were obtained according to sex, age group, reason for visit, classification of edentulous area, indication and contraindication for implant therapy, and pre-implant surgical treatment. Forty percent of the outpatients were male and 60% were female. The largest number was in the 50-59-year-old group. The reason for visit of 822 patients was request for implant therapy. 123 patients with uncomfortable implants done at other clinics, 12 patients undergoing maintenance of implants at other clinics and 43 other patients. There were 505 upper jaw cases and 529 lower jaw cases. Most anterior edentulous cases were in the upper jaw group. Most of the posterior edentulous cases were unilateral cases and many of them were free-end saddle cases. Indication patients were 447 of the 822 outpatients. The main contraindication was insufficient volume of bone. Two hundred twenty-one of the 477 indication patients did not need the pretreatment which consisted of extraction, bone graft, free gingival graft, provisional prosthetics, sinus lift, and so on.

Aim: The aim of this study was to clarify the occurrence regions and sites of peri-implant bone resorption and inflammation in partially-edentulous patients. Methods: Five hundred one partially-edentulous patients with 738 implants in function for more than 5 years were included in this study for the evaluation of the bone resorption by using dental radiograph and probing. Considering physiological bone remodeling, the mean mesio-distal bone resorption around the implant was measured on dental radiograph. Results: In 65 patients (13.0% of the total patients) with 76 implants (10.3% of the total implants), peri-implant bone resorption was identified. The mean functional loading time of these implants was 8.4 years. Occurrence regions were frequently found in the molar regions in maxilla (15.4%) and the molar region in mandible (10.0%) In these leisions detected radiologically, the bleeding on probing was seen in 95.2% of the buccal sites in mandibular molar regions, 70.0% of the palatal sites in maxillary molar regions and 56.7% of the buccal sites in maxillary molar regions with statistically significant differences. Conclusion: From the limitation of the information in this study, it was concluded that the sites that tend to be vulnerable to peri-implant inflammation were the buccal site in mandible, and the buccal and palatal sites in maxilla.

Fibroblast growth factor (FGF) signaling is involved in skeletal development. Among total 22 FGFs, it is suggested that FGF18 functions in promotion of osteoblast differentiation. In order to elucidate the mechanism of FGF18-dependent acceleration of osteogenesis, we implanted rhFGF18 soaked beads over mouse fetal coronal sutures using ex-utero surgery. The coronal suture area comprises the peripheries of the developing frontal and parietal bones, separated by the sutural mesenchyme. rhFGF18 accelerated osteogenesis by promoting connection of the frontal and parietal bone domains, resulting in elimination of the sutural mesenchyme. Expression of Fgf receptors, Fgfr1, -2 and -3 involved in skeletal development, was maintained or upregulated in the developing bone domains, consistent with enhanced osteogenesis. Bone morphogenetic protein (Bmp) 2 was specifically upregulated in the skeletogenic layer and the application of Bmp antagonist, rmNoggin, inhibited rhFGF18-dependent upregulation of osteoblast markers. These results suggest that FGF18 accelerates osteogenesis by upregulation of Bmp2 as well as maintenance or upregulation of Fgfr1, -2 and -3 expression in osteoblasts.

Dental implantation has become popular in dental treatments. Although careful planning is made to identify vital structures such as the inferior alveolar nerve or the sinus, as well as dimensions of the bone, prior to commencement of surgery, dental implantation is not fully free from risks. If a diagnostic tool is available to objectively measure bone feature before surgery and dimensions during surgery, considerable fraction of the risks may be avoided. Optical coherence tomography (OCT) is a candidate for the purpose, which enables cross-sectional imaging of bone. In this work, we performed in vitro cross-sectional imaging of extracted pig's jawbone with swept source OCT using superstructure-grating distributed Bragg reflector (SSG-DBR) laser as the source. The relatively long wavelength range of 1600nm of the laser is suitable for deeper bone imaging. We confirmed an image penetration depth of about 3 mm in physical length, which satisfies one of the criterions to apply OCT for in vivo diagnosis of bone during surgery.

A 30-year-old woman was seen in September 1995 because of a swelling of the left side of the face and an ulcer in the oral cavity. There was no sensory impairment. Computerized tomography demonstrated a large mass (75×50×50mm) in the medial side of the left parotid gland. The maxilla and the mandible were deformed by the extending tumor. Examination of a biopsy specimen showed a benign pleomorphic adenoma of salivary gland origin. Under general anesthesia the tumor was removed with the left ramus via a cervical approach using a preauricular incision. She remains well with no evidence of tumor recurrence.

A dentigerous cyst associated with a permanent tooth is frequently encountered a type of odontogenic cyst, but this cyst rarely arises in a deciduous tooth. We describe a one-year-old boy with a dentigerous cyst of a deciduous canine tooth. Marsupialization of the cyst was performed with the patient under general anesthesia. Presently, about one year after operation, the canine tooth has completely erupted and is functioning normally.

Sialadenosis, characterized by uniform hypertrophy of the acinar parenchyma of the salivary glands, is associated with a variety of systemic diseases of functional disorders.This paper describes two cases of sialadenosis, a 20-year-old woman with submandibular gland swelling and a 31-year-old woman with parotid gland swelling. Both of them had endocrine disorders that may be associated with anorexia nervosa.

Bone morphogenetic proteins have been found to be one of the most promising osteoinductive substances and they are expected to be utilized clinically for the reconstruction of defective mandibles. However, newly formed bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) has not yet been proven able to withstand the masticatory force applied by oral implants. In this study, we examined the qualitative changes in an rhBMP-2-induced mandible from the functional force of osseointegrated oral implants. Segmental (30 mm) bone defects were created in the mandibles of beagles. A poly D,L-lactic coglycolic acid-coated gelatin sponge impregnated with rhBMP-2 was grafted to the resected canine mandible. The new bone was formed 8 weeks after surgery and the Brånemark system fixtures were implanted into the reconstructed mandible. After another 8 weeks, the prosthesis was placed over the oral implants. The prosthesis was maintained in occlusion with the opposing natural dentition for 0, 4, 12, 24, or 48 weeks before the animal was euthanized. The quality of regenerated bone was then evaluated histologically and the osseointegration ratio between oral implants and the bonemeasured. During the first 4 weeks, the ratio remarkably increased from 48.9% to 64.5%. After 48 weeks, the ratio approached about 74.5%. The bone loaded for 48 weeks had undergone extensive remodeling and consolidation; its quality was better and maturer than that of bone that was not loaded. These results indicated that the newly formed bone induced by rhBMP-2 was able to withstand the masticatory force applied by oral implants and had become as functionally mature as a natural bone.

The changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate (PR) during implant surgery under local anesthesia were analyzed in 38 normal healthy patients. The results were as follows: 1. SBP significantly increased compared with the preoperative control throughout surgery. 2. DBP did not change significantly compared with the preoperative control throughout surgery. 3. PR increased just after the local anesthesia, and lowered afterward. 4. Both SBP and DBP increased in correlation with age. 5. SBP, DBP, and PR increased in correlation with surgical procedure time. 6. SBP, DBP, and PR increased in correlation with number of implantation. From these results, it was indicated that implant surgery might be accompanied by a risk, even in healthy patients.

This study was designed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) on the formation of bone in critically sized marginal defects of the mandible in dogs. Three months after extraction of the pre-molar teeth, rectangular bone defects (10 x 8 x 7 mm) were made in both sides of the mandible. A PGS block soaked in rhBMP-2 (400 microgram/ml) was implanted into one defect (BMP (+) group). As control, an untreated PGS block was implanted into the contralateral defect (BMP (-) group). 2, 4, 8, and 12 weeks after implantation, the defects were examined. In the BMP (+) group, newly formed bone was found in all defects from 4 weeks onward and was marked at 12 weeks. In contrast, the BMP (-) group showed no appreciable new bone formation, even at 12 weeks. Moreover, density of newly formed bone in the BMP (+) group was similar to that of the surrounding cortical bone at 12 weeks. These findings suggest that rhBMP-2/PGS is an effective bone substitute for reconstructive surgery of the dog mandible.

A retrospective study on medically compromised patients was made using 1,000 outpatients who visited the Clinic for Oral Implant, University Hospital, Faculty of Dentistry, Tokyo Medical and Dental University between April 1995 and June 1998. The results were as follows: 1. 35.3% (353 patients: 140 males and 213 females) of the outpatients were medically compromised. 2. The greatest number of medically compromised patients was in the 50-59 age group (118 cases), followed by those in the 40-49 and 60-69 age groups. 3. The highest ratio of medically compromised patients was in the 60-69 age group (48.2%), followed by those in the 70-79 and 50-59 age groups. 4. Among the 353 patients, 96 (27.2%) underwent surgical treatment such as insertion of implant (68 cases), removal of implant, extraction of tooth, and free gingival graft. 5. Among the 68 patients who underwent insertion of implant, in a classification by type of disease, the patients with cardiovascular diseases were the most numerous (33.9%), followed by metabolic and digestive tract diseases. 6. All surgical treatments of implant insertion were performed under local anesthesia, while monitoring cardiac and respiratory function, and SpO2. Among the 68 patients, 9 underwent operation under intravenous sedation and 2 under nitrous oxide inhalation sedation. All 11 patients had hypertension. The results suggested that identification of preoperative risk factors, precise recognition of general condition, and establishment of control system are important to manage medically compromised patients for dental implant treatment.