記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/jbm.a.36597

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1089/wound.2018.0834.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： DOI: 10.1002/jcp.26571

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background
The surface roughness of a dental implant affects the epithelial wound healing process and may significantly enhance implant prognosis.
Purpose
We explored the influence of surface roughness on peri-implant epithelium (PIE) sealing and down-growth by comparing machine-surfaced (Ms) and rough-surfaced (Rs) implants.
Materials and Methods
(1) Maxillary first molars were extracted from rats and replaced with Ms or Rs implants. (2) We also compared changes in the morphology of cultured rat oral epithelial cells (OECs) grown on Ms or Rs titanium (Ti) plates.
Results
(1) After 4 weeks, the PIE around Ms and Rs implants showed a similar structure to junctional epithelium (JE). At 16 weeks, Rs implants appeared to form a weak epithelial seal at the tissue-implant interface and exhibited markedly less PIE down-growth than Ms implants but was deeper than that observed in natural teeth. (2) We observed less expression of adhesion proteins in OECs cultured on Rs plates than in cells grown on Ms plates. Additionally, cell adherence, migration, and proliferation on Rs plates were lower, whereas apoptosis was reduced on Ms plates.
Conclusion
Ms implants are a better choice for integration with an epithelial wound healing process.

DOI： 10.1111/cid.12043

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Effects of small vibration stimuli on bone formation have been reported. In the present study, we used morphological and morphometric procedures to elucidate whether low-magnitude, high-frequency (LMHF) vibration stimuli could enhance the bone healing of rat incisor extraction sockets. After extraction of incisors from six-week-old rats, animals were assigned into a control group and two experimental groups to receive 50 Hz stimuli at either 0.05 mm or 0.2 mm peak-to-peak for an hour/day. LMHF vibration stimuli were generated by placing the mandibles of the animals onto a vibration generator. All groups were subdivided into two, according to the study periods (1 and 3 weeks). After the study period, undecalcified ground sections were taken and morphological and morphometric analyses performed. At both 1 and 3 weeks, newly formed bone was observed mainly in the upper wall of the extraction socket in all groups. Morphometric analyses revealed that the trabecular thickness in both experimental groups at 1 week was significantly greater than that in the control. LMHF vibration stimuli had a positive effect on bone at the early stage of bone healing, particularly in trabecular thickness, at the incisor extraction socket.

DOI： 10.1115/1.4007247.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: Implant designs that can stimulate and integrate with an epithelial wound-healing process may significantly enhance the efficacy of dental implants. Here, we evaluated the potential of ‘‘step-type’’ implant systems to improve the sealing between the peri-implant epithelium (PIE) and the implant surface, and investigated the effect of implant structure on PIE down-growth.
Materials and methods: Right maxillary first molars were extirpated from rats and implanted with either a straight-type or a step-type implant varying in step height and/or width (Ns: 0.8 mm height, 0.1 mm width; Ws: 0.8 mm height, 0.2 mm width; Hs: 0.4 mm height, 0.1 mm width). Maxillae were harvested at various time points over 16 weeks to evaluate laminin-5 distribution as an indicator
of wound healing and PIE formation, horse-radish peroxidase (HRP) penetration as a measurement of epithelial sealing, and PIE down-growth formation.
Results: In all implant models, the PIE formed from the oral sulcular epithelium and spread apically along the implant surface. In the Ws group, HRP penetration was detected only in the coronal region of the PIE at 4 weeks, whereas in the straight-type, it was observed in the apical region and the connective tissue. At 16 weeks, the Ws implants exhibited markedly less PIE down-growth than the Con, Ns or Hs implants, and were equivalent to that observed in natural teeth.
Conclusion: The step-type implant system may have the potential for improving epithelial sealing at the tissue–implant interface, as well as reducing apical PIE down-growth, thus enhancing dental implant efficacy.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of this study was to evaluate the effects of newly developed injectable poly (lactic-co-glycolic acid) (PLGA) microspheres containing fluvastatin on osteogenesis around titanium implants in the rat tibia. After confirmation of the sustained-release profile of fluvastatin from the microspheres by an in vitro assay, the microspheres were administered to the back skin of the rats by a single transdermal injection. At 2 and 4 weeks after the implant surgery, the fluvastatin groups showed enhanced new bone formation around the titanium implants without any influence on the serum biochemistry. In addition, the fluvastatin groups showed increased three-point bending strengths of their femurs. The results of this study indicate that a single remote injection of PLGA/fluvastatin microspheres safely and successfully stimulated bone formation around titanium implants and increased the mechanical properties of bone.

DOI： http://dx.doi.org/10.1016/j.biomaterials.2010.01.016

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Summary  Statins are cholesterol-lowering drugs that have been reported to promote bone formation. The purpose of this study was to investigate the effect of simvastatin on the enhancement of bone formation around titanium implants. Thirty-week-old female rats received pure titanium implants in both tibiae. The animals were intra-peritoneally administered 0, 0·125, 1, 5 or 10 mg kg−1 of simvastatin daily. After 30 days, the animals were sacrificed, and specimens were prepared. The bone contact ratio of the implant, bone density in the medullary canal and percentage of cortical bone were obtained. Markers for bone turnover were also measured using sera collected at the time of euthanasia. In the medullary canal, a scanty amount of bone was observed in the 0, 0·125 and 1 mg kg−1 groups. In contrast, in both the 5 and 10 mg kg−1 groups, thicker bone trabeculae were abundant. Histometric observations showed that the bone contact ratio and the bone density of both groups were significantly greater than those of the other groups (anova, P < 0·01). However, no significant difference in the percentage of cortical bone was found between groups. Serum chemistry showed that statin increased bone formation markers and decreased bone resorption markers. In conclusion, although the dose equivalent to that used in human patients with hypercholesterolemia was not effective, a simvastatin dose of 5 mg kg−1 or higher increased medullary bone formation around the titanium. In contrast, no effect of simvastatin on pre-existing cortical bone was indicated.

DOI： DOI: 10.1111/j.1365-2842.2009.02011.x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective
We investigated whether the local administration of simvastatin affected both the cellular events and the bone formation at surgically created bone defects in rat.

Study design
Simvastatin (or a vehicle) was injected into a rat bony defect for 3 consecutive days from the day of surgery. Five or ten days after the injection, new bone tissue was collected, and the gene expressions of bone-related proteins were examined. For the histomorphometry, new bone area was measured.

Results
At day 5, the statin group demonstrated significantly larger new bone area. The number of tartrate-resistant acid phosphatase–positive multinucleated cells in the statin group was less than in the control group. In the statin group, the expressions of both alkaline phosphatase and bone morphogenetic protein 2 mRNA significantly increased. In contrast, the expression of cathepsin K was significantly suppressed in the statin group. Although the levels of both RANK and osteoprotegerin were not affected by statin, the expression of RANKL was depressed. At day 10, there were no significant differences among the groups in either histomorphometric or reverse-transcription polymerase chain reaction analyses.

Conclusion
New bone area increased under the influence of simvastatin; however, the effect did not continue when the administration was terminated. Osteoclast suppression may be the consequence of RANKL depression.

DOI： http://dx.doi.org/10.1016/j.tripleo.2008.07.013

開催年月日： 2009年4月

国名：大韓民国  

開催年月日： 2008年7月

国名：カナダ  

開催年月日： 2008年6月

国名：日本国  

開催年月日： 2007年10月

開催地：CCIB Barcelona Form   国名：スペイン  

開催年月日： 2007年9月

国名：日本国  

開催年月日： 2006年7月

国名：オーストラリア連邦  

開催年月日： 2006年7月

国名：日本国  

開催年月日： 2005年5月

国名：ギリシャ共和国  

開催年月日： 2019年5月

記述言語：日本語  

開催地：札幌コンベンションセンター（北海道）   国名：日本国  

開催年月日： 2019年1月

記述言語：日本語  

開催地：浦添市てだこホール(沖縄)   国名：日本国  

開催年月日： 2018年10月

記述言語：英語  

開催地：MESSE WIEN EXHIBITION & CONGRESS CENTER (Vienna)   国名：日本国  

開催年月日： 2017年10月

記述言語：日本語  

国名：中華人民共和国  

開催年月日： 2017年9月

記述言語：日本語  

開催地：仙台国際センター   国名：日本国  

開催年月日： 2017年8月

記述言語：日本語  

開催地：鹿児島大学   国名：日本国  

開催年月日： 2017年6月 - 2017年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：パシフィコ横浜   国名：日本国  

口腔インプラントは，歯根膜を有する天然歯と異なり オッセオインテグレーションをしているため，負荷され た咬合力はインプラント体を通して骨に直接伝達され る.また，インプラントのスレッド形態は周囲骨にマイク ロクラックを生じやすいことが報告されている1).このよ うな特徴を持つインプラント周囲骨であるが，荷重負 荷時の骨動態については未解明な点が多い.近年， 骨において機械的刺激を受容するメカニズムとしての 骨細胞の働きが注目されており，骨細胞が破骨細胞 や骨芽細胞の機能を制御することによってリモデリン グを調節すると考えられている.また，骨細胞はマイク ロクラックを感知しターゲットリモデリングのトリガーとな ることも知られている2).そこで，本研究では，咬合力 を負荷したインプラント周囲骨細胞動態をin vivo，in vitro両面で解析し，インプラント周囲に特化した骨代 謝のメカニズムを明らかにすることとした. 　動物実験として，4週齢雄性Wistarラットの第一臼歯を 抜去し，4週後にチタンインプラントを埋入した.オッセ オインテグレーション獲得を確認した後に咬合負荷を 開始し，4週間機能後にインプラント周囲骨細胞の形 態学的および組織学的，免疫組織化学的検討を行っ た(n=4-12). 培養実験では，骨細胞様細胞株MLO-Y4三次元ゲ ル包埋培養を行い，骨細胞間連絡機構，三次元ネッ トワーク構造を再現した.インプラントのスレッドを模し たチタンプレートにて反復刺激を与える装置を開発 し，MLO-Y4三次元培養ゲルに機械的刺激を付与し た.1Hzの反復刺激を付与した後，細胞の生死，免疫 組織化学的検討，遺伝子発現解析，刺激後の培養 上清を用いた骨髄細胞培養を行った.骨細胞間連絡 を阻害するヘプタノールを用いて，骨細胞ネットワー クの機能についても検討した(n=4). 統計学的解析には，ヘプタノール添加実験におい て一元配置分散分析，荷重の有無による比較におい てt検定を用い，p<0.05を有意差ありとした. 　動物実験において，SEM観察下にてインプラント体に 近接して骨細胞ネットワークを認めた.咬合荷重群で は，インプラント周囲にsclerostin，connexin43の発現 を強く認めた.荷重群ではアポトーシスを起こした骨細胞を認め，TRAP陽性細胞を有意に多く認めた.こ れらより，咬合荷重下のインプラント周囲骨細胞は，骨 形成を抑制し，骨吸収を促進する方向への働きがあ ることが示唆された. 培養実験では，プレートに反復運動を与えると周囲 の細胞におけるアポトーシスの増加，RANKLの遺伝 子発現上昇を認めた.ヘプタノールを加えると connexin43の発現が減少，死細胞数が増加し，機械 的刺激への抵抗性の低下が考えられた.これらの結 果より，骨細胞間連絡が骨代謝の調節に重要な役割 を果たすことが示唆された. 以上より，骨細胞ネットワークが咬合力を感知するこ とで周囲骨リモデリングの起点となる骨吸収が開始さ れ，インプラント周囲における骨代謝へ寄与すること が示唆された.

開催年月日： 2017年6月

記述言語：英語  

開催地：Soule   国名：大韓民国  

Objectives: Dental implants are osseointegrated and the occlusal force acting on dental implants is directly and intricately transmitted to the bone. Therefore we hypothesized that this occlusal stress involved in peri-implant bone homeostasis. Osteocytes are well-known for their mechanoreceptor functions, and the three-dimensional network via gap junction of osteocytes is crucial for detecting and orchestrating mechanical response of bone. The aim of this study was to investigate the role of osteocyte network around the implant in stress-related bone remodeling. Methods: Using maxillary implant model of rat, we compared loaded implants with unloaded ones after 8 weeks of implantation (n=4/gp). Behavior of osteocytes and peri-implant bone were assessed by histological and immunohistochemical analyses. To simulate the response of osteocyte network around the implant, we established an apparatus for stimulating 3-D cultured MLO-Y4 osteocytic cells. Cells were subjected to cyclic stress (1Hz, 24hrs) by an edged titanium plate designed like dental implant (n=4/gp). Stress-induced effects on osteocyte network were investigated by quantitative PCR, viability, immunohistochemical, and TRAP/ALP analyses. We performed t-test to compare effects of load and ANOVA to evaluate effects of load and fuctions of the gap junction in each analysis (p<0.05 as significance).　 Results: We observed that osteocytes formed developed network around implants and plates. Application of physiological loading increased connexin43 (gap junction component) expression in vitro and in vivo. There were more TRAP positive sites and apoptotic osteocytes around the loaded implants and loading increased RANKL expression. Gap junction inhibitor increased dead cells and TRAP activity and reduced the resistance of stress-induced damage and ALP activity in vitro. Conclusions: These results suggest that osteocyte network via gap junction is responsible for the stress-induced communication and activates bone remodeling around implants.

開催年月日： 2016年9月 - 2017年6月

記述言語：日本語  

開催地：名古屋   国名：日本国  

開催年月日： 2015年10月

記述言語：英語  

開催地：Fukuoka, Japan   国名：日本国  

開催年月日： 2015年3月

記述言語：英語  

開催地：Boston   国名：アメリカ合衆国  

Objectives: Osteocytes are believed to be the mechanosensors and responsible for coordinating the bone remodeling process. The occlusal force acting on dental implants directly and intricately transfer to the alveolar bone. We hypothesized that osteocytes neighboring implant should play an important role in detecting local mechanical environment and in initiating bone remodeling process. The aim of this study was to investigate the effects of occlusal force induced biochemical response from osteocytes in vitro. Materials and Methods: We established 2 type of loading apparatuses, in which MLO-Y4 cells were three-dimensionally cultured, subjected to cyclic mechanical stress in physiological strain assumed occlusal force for 24 hours. Type 1 can simultaneously apply five different strain magnitudes for mechanical stretching of the cells. MLO-Y4 cells were subjected to stretching of physiological strain (from 0.095% to 1.22%). Type 2 is an apparatus that the screw which shaped titanium plate imitated dental implant received cyclic stress in the gel embedded MLO-Y4 cells. Cell viability assay and real-time RT-PCR analyses were examined. Additionally, the conditioned mediums from stimulated cultures were added to bone marrow cultures and ALP activity was quantified. Moreover, inhibition of gap junction channels was performed using the inhibitor heptanol. Results: Cyclic stress in physiological strain induced the death of MLO-Y4 cells, using both apparatuses. Real-time RT-PCR analyses showed that the mechanical strain stimulated RANKL/OPG ratio and suppressed sclerostin expression in a magnitude-dependent. Expression of connexin43 was increased the middle strain magnitude. Determinate quantity of ALP demonstrated that condition medium from the cyclic stretch culture induced ALP activity in low magnitude. On the other hands, it showed low ALP activity when inhibited intercellular signaling by heptanol. Conclusion: These results suggest that osteocyte may play a role in regulating bone remodeling under physiological strain by the intermediary of gap junction.

開催年月日： 2015年2月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：福岡   国名：日本国  

開催年月日： 2013年10月

記述言語：英語  

開催地：Dublin   国名：アイルランド  

開催年月日： 2012年10月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Fukuoka   国名：日本国  

開催年月日： 2012年5月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：横浜   国名：日本国  

開催年月日： 2012年4月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡   国名：日本国  

開催年月日： 2011年11月

開催地：長崎   国名：日本国  

開催年月日： 2011年10月

開催地：福岡   国名：日本国  

開催年月日： 2011年9月

開催地：名古屋   国名：日本国  

開催年月日： 2011年5月

会議種別：口頭発表（一般）  

開催地：広島   国名：日本国