Lysine Demethylase 4A is a Centrosome Associated Protein Required for Centrosome Integrity and Genomic Stability.

Centrosomes play a fundamental role in nucleating and organizing microtubules in the cell and are vital for faithful chromosome segregation and maintenance of genomic stability. Loss of structural or functional integrity of centrosomes causes genomic instability and is a driver of oncogenesis. The lysine demethylase 4A (KDM4A) is an epigenetic 'eraser' of chromatin methyl marks, which we show also localizes to the centrosome with single molecule resolution. We additionally discovered KDM4A demethylase enzymatic activity is required to maintain centrosome homeostasis, and is required for centrosome integrity, a new functionality unlinked to altered expression of genes regulating centrosome number. We find rather, that KDM4A interacts with both mother and daughter centriolar proteins to localize to the centrosome in all stages of mitosis. Loss of KDM4A results in supernumerary centrosomes and accrual of chromosome segregation errors including chromatin bridges and micronuclei, markers of genomic instability. In summary, these data highlight a novel role for an epigenetic 'eraser' regulating centrosome integrity, mitotic fidelity, and genomic stability at the centrosome.

Clinical Safety Assessment of Autologous Freeze-Drying Platelet-Rich Plasma for Bone Regeneration in Maxillary Sinus Floor Augmentation: A Pilot Study.

The purpose of this clinical study is to evaluate the safety and preliminary efficacy of autologous freeze-drying platelet-rich plasma (FD-PRP) on bone regeneration in maxillary sinus floor augmentation as a preliminary pilot study. Five patients that required sinus floor augmentation to facilitate the placement of dental implants participated in this clinical study. The PRP was prepared from the autologous peripheral blood and was lyophilized and stored at -20 °C for 4 weeks before surgery. At surgery, triple-concentrated FD-PRP (x3FD-PRP) mixed with synthetic bone grafting materials was rehydrated following the transplantation into the sinus floor. The primary outcome was a safety verification of x3FD-PRP, evaluated in terms of the clinical course and consecutive blood tests. The secondary outcome was clinical efficacy focused on bone regeneration in sinus floor augmentation evaluated by radiographic examination and implant stability. There were no adverse events, such as systemic complications, excessive inflammatory reactions, severe infection, or local site healing complications, besides those on the usual course associated with surgery. Vertical augmented height was maintained, and the initial stability of implants was achieved post-operatively in 6 months. The results obtained in this study suggest that x3FD-PRP can be used safely for bone engineering in clinical practice. Further studies are required to draw a conclusion concerning the efficacy of x3FD-PRP since this was a pilot study with a single arm and a small sample size.

Alveolar bone preservation by a hydroxyapatite/collagen composite material after tooth extraction.

OBJECTIVE: The aim of this study was to assess the effectiveness of a hydroxyapatite/collagen composite material (HAp/Col) for preservation of alveolar bone after tooth extraction. MATERIALS AND METHODS: HAp/Col was applied to the alveolus bone ridge preservation after tooth extraction, because of subsequent dental implant placement in 35 regions of 24 patients (mean age, 59.3 years; range, 25-81 years). Cone beam computed tomography was used to assess changes in alveolar bone at the extraction site before and at 3 months (mean, 13.7 weeks; range, 10-17 weeks) after tooth extraction. Changes in height and width of the alveolar bone were measured to evaluate bone reduction after surgery. Bone biopsy was performed at 11 regions of dental implant placement to observe bone regeneration and remaining material in the extraction socket. RESULTS: The alveolar bone height was decreased by 0.00 ± 2.44 mm at the buccal side and 0.35 ± 1.73 mm at the lingual side, while the width was decreased by 1.02 ± 1.64 mm at 3 months after surgery. The middle of the socket floor was elevated by 5.71 ± 3.45 mm at 3 months after surgery. Bone biopsy specimens revealed no remaining implanted material, and approximately 49.79 ± 14.41% of the specimens were occupied by bone tissue. CONCLUSIONS: According to the result of this study, HAp/Col is a reliable material to presearve alveolar bone after tooth extraction. CLINICAL RELEVANCE: HAp/Col contributes dental implant treatment due to maintain the alveolar bone after tooth extraction.

Clinical study of guided bone regeneration with resorbable polylactide-co-glycolide acid membrane.

The guided bone regeneration (GBR) technique is often applied to provide sufficient bone for ideal implant placement. The objective of this study was to evaluate whether GC membrane®, which has already been used for guided tissue regeneration (GTR), can also be available for GBR. Twenty-three implants in 18 patients were evaluated in the study. All patients underwent implant placement with GBR using GC membrane®. Cone-beam computed tomography was performed at 13-30 weeks after surgery and the amount of augmented bone was assessed. The implant stability quotient (ISQ) was measured at the second operation to evaluate implant stability. Although wound dehiscence was observed at 4 of 23 regions (17.4%), all wounds closed quickly without any events by additional antibiotic administration. GBR-induced bone augmentation of 0.70-2.56 mm horizontally and 0-6.82 mm vertically. Only 0.18 mm of bone recession was observed at 16-24 months after implant placement. GBR with GC membrane® induced sufficient bone augmentation, leading to successful implant treatment. The present results suggest that GC membrane® is available not only for GTR, but also for GBR.

Efficacy of freeze-dried platelet-rich plasma in bone engineering.

OBJECTIVE: Platelet-rich plasma (PRP) is typically isolated and applied immediately after preparation, making it both a time- and labor-intensive addition to the operative procedure. Thus, it would be convenient if PRP could be preserved. We evaluated the efficacy of freeze-dried PRP (FD-PRP), as compared with freshly isolated PRP (f-PRP) for bone engineering. DESIGN: FD-PRP was prepared by lyophilization of f-PRP and was subsequently preserved at -20°C for one month. It was then rehydrated with an equal or 1/3 amount of distilled water (×1FD-PRP, ×3FD-PRP, respectively), and we assessed its gelation properties and the release of growth factors (PDGF-BB, TGF-ß1, and VEGF). We also examined the bone forming ability with onlay-grafting on mice calvaria using ß-TCP granules as a scaffold. RESULTS: FD-PRP showed comparable gelation as f-PRP. In terms of growth factor release,×1FD-PRP released identical concentrations of PDGF-BB and TGF-ß1 to f-PRP, while ×3FD-PRP released approximately 3-fold concentrations when compared with f-PRP. In vivo, ×1FD-PRP promoted identical levels of the bone formation as f-PRP, and ×3FD-PRP induced more abundant bone formation. CONCLUSIONS: These results suggest that f-PRP can be stored without functional loss by freeze-drying and the concentration of PRP may improve its efficacy in bone engineering.

Bone Regeneration Using Dentin Matrix Depends on the Degree of Demineralization and Particle Size.

OBJECTIVES: This study aimed to examine the influence of particle size and extent of demineralization of dentin matrix on bone regeneration. MATERIALS AND METHODS: Extracted human teeth were pulverized and divided into 3 groups according to particle size; 200, 500, and 1000 µm. Each group was divided into 3 groups depending on the extent of demineralization; undemineralized dentin (UDD), partially demineralized dentin matrix (PDDM), and completely demineralized dentin matrix (CDDM). The dentin sample was implanted into rat calvarial bone defects. After 4 and 8 weeks, the bone regeneration was evaluated with micro-CT images, histomorphometric and immunohistochemical analyses. Osteoblasts were cultured on UDD and DDM to evaluate the cell attachment using electron microscope. RESULTS: Micro-CT images and histological observation revealed that CDDM had largely resorbed but UDD had not, and both of them induced little bone formation, whereas all particle sizes of PDDM induced more new bone, especially the 1000 µm. Electron microscopic observation showed osteoblasts attached to DDM but not to UDD. CONCLUSIONS: PDDM with larger particle size induced prominent bone regeneration, probably because PDDM possessed a suitable surface for cell attachment. There might be an exquisite balance between its resorption and bone formation on it. PDDM could be considered as a potential bone substitute.

The three-dimensional assessment of dynamic changes of the proximal segments after intraoral vertical ramus osteotomy.

OBJECTIVES: The aim of this study was to assess the positional changes of the proximal segments after intraoral vertical ramus osteotomy (IVRO). METHOD: Fifteen patients underwent IVRO and were followed according to the authors' unique postoperative management regimen. The analyses of the positions and angles of the proximal segments were performed on frontal and lateral cephalograms, which were taken before surgery (T1) and within 3 days (T2), at 4 weeks (T3), and later than 6 months after surgery (T4). The three-dimensional positions of the condylar heads were also assessed by CT images, which were taken before and 1 year after surgery. RESULTS: The proximal segments temporarily swung posteriorly and laterally with a center on the condylar head as a fulcrum point at T2 and T3, compared with T1, and they repositioned at T4. The condylar heads moved inferior approximately 2 mm with lateral rotation one year after surgery, as seen in the CT. DISCUSSION: The condylar heads changed their positions physiologically for newly established jaw movement after IVRO with the authors' post-operative management regimen because the post-operative skeletal stability and the jaw function were good and stable using this method.

Effects of Vertical Movement of the Anterior Nasal Spine on the Maxillary Stability After LeFort I Osteotomy for Pitch Correction.

Few reports have so far evaluated the maxillary stability after LeFort I osteotomy (L-1) for pitch correction. In the current study, the authors assessed the SN-PP (palatal plane) to evaluate the skeletal stability after osteotomy with clockwise or counter-clockwise rotation and investigated the effects of anterior nasal spine (ANS) and posterior nasal spine (PNS) movement on the stability of the SN-PP.The SN-PP and the positions of ANS, PNS, and point A were measured on lateral cephalograms before surgery (T1), immediately after surgery (T2), and more than 1 year after surgery (T3).All measured angle and points were stable in 4 cases of counter-clockwise rotation. In the 16 cases of clockwise rotation, T3-T2 of SN-PP, ANS, and point A was -2.05°, -2.56 mm, and -1.64 mm, when the SN-PP increased more than 4° after osteotomy. When the ANS moved downward more than 3 mm, the ANS and point A relapsed significantly by 2.75 and 2.31 mm, while the SN-PP relapsed 1.61° more than 1 year after surgery.When the SN-PP increased by more than 4° or the ANS moved downward by more than 3 mm, the authors suggest shifting the PNS upward instead of moving the ANS downward.

Oral Rehabilitation With Orthognathic Surgery After Dental Implant Placement for Class III Malocclusion With Skeletal Asymmetry and Posterior Bite Collapse.

Increasing numbers of older patients are seeking orthognathic surgery to treat jaw deformity. However, orthodontic and orthognathic surgical treatment is difficult in cases without occlusal vertical stop. A 55-year-old man presented with Class III malocclusion and mandibular protrusion including esthetic problems and posterior bite collapse. He underwent dental implant treatment to reconstruct an occlusal vertical stop before orthognathic surgery. His occlusal function and esthetic problems improved after surgery, and his skeletal and occlusal stability has been maintained for 6 years. Dental implant placement at appropriate positions could help to determine the position of the proximal segment at orthognathic surgery and could shorten the time required to restore esthetic and occlusal function. This case demonstrates how skeletal and dental stability can be maintained long after surgery in a patient with jaw deformity and posterior bite collapse.

The skeletal stability after maxillo-mandibular osteotomy with a "physiological positioning strategy".

The aim of this study was to estimate skeletal and dental stability after maxillomandibular osteotomy with physiological positioning. Ten patients (7 men and 3 women) with skeletal mandibular prognathism were treated by conventional Le Fort I osteotomy for the maxilla and unfixed short lingual osteotomy for the mandible together with physiological positioning. We used cephalometric analysis to evaluate the skeletal and dental stability preoperatively, immediately after maxillomandibular osteotomy, and more than 1 year later. The immediately postoperative measurements for the SNA and the SN-palatal planes were 0.15° (p=0.67) and 1.0° (p=0.17), respectively. The positions of the anterior nasal spine, posterior nasal spine, and A point showed minimal changes 1 year postoperatively. The postoperative difference for SNB was 0.76° (p=0.04). Dental stability was apparent postoperatively. We conclude that reliable stability of both the maxilla and the mandible was achieved after maxillomandibular osteotomy with physiological positioning in patients with mandibular prognathism.

Short lingual osteotomy without fixation: a new strategy for mandibular osteotomy known as "physiological positioning".

We describe the strategy of physiological positioning, which we regard as a new alternative treatment to conventional orthognathic operations, and treated 18 patients with skeletal mandibular prognathism using it. The positions of SNB, FMA, and Me were measured postoperatively to assess skeletal stability, changes in the angle and perpendicular length of the upper and lower central incisors were measured to assess dental stability, and we confirmed that both skeletal and dental stability were excellent. The width to which the jaw could be opened recovered early, and we saw only one case of disorder of the temporomandibular joint. Short lingual osteotomy with physiological positioning is an effective new approach to the treatment of deformities of the mandible.

The migration pathway of an extracted maxillary third molar into the buccal fat pad.

The migration of the maxillary third molar is one of the most critical complications that can occur during extraction, and the most frequent site of migration is the maxillary sinus. We herein report an extremely rare case in which the migrated maxillary third molar became displaced into the buccal fat pad. The pathway of migration from the original site of the tooth into the buccal space is therefore considered from the anatomical perspective in this paper.