Research Projects -
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Grant number：24659875 2012.04 - 2014.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
SONOYAMA Wataru, KUBOKI Takuo, ONO Mitsuaki
Grant amount：\3770000 （ Direct expense: \2900000 、 Indirect expense：\870000 ）
It is well known that adult tissue stem cells, which exit in the niche, are involved in the maintenance or restoration of homeostasis in various tissue. In this research, we focused Ccn4 gene and that revealed that Ccn4 gene could be involved in tooth development and wound healing. In future, we will clarify the relationship between Ccn4 gene and maintenance mechanism of niche.
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Grant number：24792142 2012.04 - 2014.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B) Grant-in-Aid for Young Scientists (B)
OIDA Yasutaka, KUBOKI Takuo, SONOYAMA Wataru, ONO Mitsuaki, SHINKAWA Shigehiko, NAKAJIMA Ryu
Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）
CCN2 / connective tissue growth factor (CTGF) has been reported to have essential role in cartilage development, chondrocyte proliferation and differentiation as well as regulation of the extracellular matrix metabolism. This study screened a compound library and identified harmine as a novel inducer of CCN2. This finding indicates harmine as a potential drug for prevention and / or repair of cartilage degradation.
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Grant number：23792227 2011.04 - 2015.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B) Grant-in-Aid for Young Scientists (B)
MINE Atsushi, YATANI Hirofumi, KUBOKI Takuo, YOSHIDA Toshimasa, KUROSAKI Youko, MINO Takuya
Grant amount：\2990000 （ Direct expense: \2300000 、 Indirect expense：\690000 ）
Three-unit resin-bonded fixed partial prosthesis (Rb-FPP, n = 86) and Three-unit conventional fixed partial prosthesis (Co-FPP, n = 100) installed at the Fixed Prosthodontic Clinic of Okayama University Dental Hospital between April 1989 and March 1992 were clinically evaluated. The corresponding survival rate for Rb-FPP and Co-FPP were 69 % and 72 % after 10 years and 50 % and 46 % after 25 years respectively. There was no significant difference between the two groups (p = 0.88).
Regarding to the incidence of complications, “removal of FPP” was significantly higher for Co-FPP (p = 0.01). Cox proportional hazards test revealed that “FPP type”, “sex”, “age”, “number of remaining teeth”, “insertion position” and “abutment teeth condition” were not significant predictors of FPP failure (p = 0.82). -
Grant number：23390442 2011.04 - 2015.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
MINAKUCHI Hajime, KUBOKI Takuo, SOGAWA Chiharu, MAEKAWA Kenji, SOGAWA Norio, KITAYAMA Shigeo
Grant amount：\18200000 （ Direct expense: \14000000 、 Indirect expense：\4200000 ）
This aimed to evaluate the correlation between SERT uptake ability in human peripheral platelets and SB frequency. Subjects were consecutively recruited from sixth-year students. SB frequency was determined as the summary score of 3-consecutive night assessments using a self-contained EMG detector/analyzer in their home environment. Fasting peripheral venous blood samples were collected in the morning following the final SB assessment. Amount of SERTs and platelets were quantified by ELISA assay. Functional characterization of SERT, 5-HT uptake, maximum velocity (Vmax) and affinity constant (Km) were assessed by [3H] 5-HT uptake assay. The correlation between these aforementioned variables and SB level was evaluated.
A small but significant negative correlation between SB level and [3H] 5-HT uptake was observed (p<0.05, R2=0.063, Spearman correlation). Platelet serotonin uptake is significantly correlated to SB frequency, although it only explains a small amount of SB variability. -
Functional regeneration of the oral cavity marginal muscles by cybernics approach
Grant number：23659898 2011 - 2013
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
MAEKAWA KENJI, OKA Hisao, KUBOKI Takuo
Grant amount：\3640000 （ Direct expense: \2800000 、 Indirect expense：\840000 ）
While attempts were made to establish the electrical stimulation methods to induce the reactive muscle activity for the patients with muscle dysfunction in orofacial regions by systemic disease such as a stroke, it was difficult to achieve it. Therefore, we next conceived to evaluate the degree of burden for care-givers to nursing to the persons requiring care with masticatory disturbance. By carrying out this investigation, we thought that we could appeal the importance of the rehabilitation of oral function and could indirectly lead to the development of novel rehabilitation methods. The results of the investigation to evaluate the degree of burden for the care-givers to persons requiring care suggested that time necessary to feeding and oral care, and the number of remaining teeth significantly associated with the degree of burden.
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Grant number：23890123 2011 - 2012
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up Grant-in-Aid for Research Activity Start-up
NAWACHI Kumiko, OIDA Yasutaka, SONOYAMA Wataru, KUBOKI Takuo
Grant amount：\3250000 （ Direct expense: \2500000 、 Indirect expense：\750000 ）
BMP-2 is widely known as an osteogenic inducer, but conflicting results are related to its function inside the bone marrow space. This study aimed to clarify the molecular mechanisms and impact of BMP-2 on bone metabolism environment of the bone marrow space. Of great interest, we found that BMP-2 inhibits bone formation in bone marrow space. To date, in an attempt to elucidate this mechanism, we are focusing on BMP-2 negative feedback regulation as well as on cellular and molecular interactions from an immunological perspective.
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Development of a technic to generate somatic stem cells using a newly reprogramming method.
Grant number：23659899 2011 - 2012
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
KUBOKI Takuo, SONOYAMA Wataru, UCHIBE Kenta, ONO Mitsuaki
Grant amount：\3640000 （ Direct expense: \2800000 、 Indirect expense：\840000 ）
We performed a screening for factors involved in the regulation of maintenance of stemness in dental pulp cells (DPCs). As a result, we found that TNF-αwas involved in maintenance of stemness, and increased the number of cells positive for stem cell surface markers CD146 and SSEA4. Moreover, we also identified some microRNAs that regulate stemness, proliferation and differentiation of DPCs.
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Development of neuro-regeneration with Botulinum toxin
Grant number：23659897 2011 - 2012
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
MATSUKA Yoshizo, KUBOKI Takuo, MATSUO Ryuji, OGUMA Keiji, YAMAMOTO Yumiko, KUMADA Ai
Grant amount：\3510000 （ Direct expense: \2700000 、 Indirect expense：\810000 ）
Dissociated rat trigeminal ganglion somata were incubated with matrigel in 37℃ CO_2condition. Commercially available hippocampus neuron was used in this study. Neuronal change was observed and the neuron that incubated with type A Botulinum toxin was survived longer than control. Also, dendrite of the neuron with Rotulinum toxin was longer than control neuron.
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低分子化合物ライブラリーを用いた骨形成過程における新規BMP2活性制御因子の探索
Grant number：23592844 2011
日本学術振興会 科学研究費助成事業 基盤研究(C) 基盤研究(C)
藤澤 拓生, 園山 亘, 窪木 拓男, 服部 高子
Grant amount：\5070000 （ Direct expense: \3900000 、 Indirect expense：\1170000 ）
骨欠損部に対して骨形成タンパク(BMP)を用いて骨造を図る方法は次世代の骨造法の最も有望な方法と考えられているが,ターゲットとする細胞の応答性の低さから大量のタンパクが必要となり高コストとなること,および大量のタンパク投与による副作用のリスクが高まる危険があり,より低用量で高効果の得られる投与方法の開発が望まれている。そこで本研究はBMPの生理活性を増強する低分子化合物を同定し,その機能を解明することを目的に以下の実験を行った。
まず初めに一次スクリーニングとして低分子化合物(FDA approved Drug Library)の細胞増殖能,細胞障害度ならびにBMP-2の生物学的活性に与える影響について検討した。細胞増殖能についてはMTS assayで,細胞障害度に関してはLDH assayでそれぞれ評価した。BMP-2の生物学的活性に関してはBMP-2シグナルの増強の有無をBMP-2にのみ特異的な反応を示すId-1プロモーター領域を有するレポーター遺伝子を導入したC2C12細胞を用いたルシフェラーゼアッセイで評価した。その結果,640個の低分子化合物ライブラリーから細胞に障害を与えることなくBMP-2の生物学的活性を相乗的に増強する,あるいは化合物単体でBMP-2様の生物学的活性を示す可能性のある化合物を40個抽出した。さらに二次スクリーニングとしてin vitroでアルカリホスファターゼ活性の測定とアリザリンレッド染色による石灰化能の検討を行い40個の候補化合物からBMP-2の骨形成能を増強している可能性のある化合物を7個抽出した。 -
Grant number：22249064 2010.04 - 2014.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A) Grant-in-Aid for Scientific Research (A)
KUBOKI Takuo, TAKIGAWA Masaharu, SONOYAMA Wataru, TSUJI Takashi, ASAHARA Hiroshi
Grant amount：\46670000 （ Direct expense: \35900000 、 Indirect expense：\10770000 ）
In the dental field, the regeneration of complete tooth is ultimate goal. First, we examined whether fully functional bioengineered tooth could regenerate utilizing an organ germ method with the permanent tooth bud tissue of the post-natal canine, we succeeded in it, for the first time in the world. Next, in order to understand the mechanism of tooth development, we performed the screening and clarified that several Hox gene specifically expressed in the development of tooth.
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Development of a new treatment for trigeminal neuron sensitization
Grant number：22390365 2010.04 - 2014.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
MATSUKA Yoshizo, KUBOKI Takuo, YAMAMOTO Yumiko, KUMADA Ai, OGUMA Keiji
Grant amount：\18720000 （ Direct expense: \14400000 、 Indirect expense：\4320000 ）
Fluorescein labeled botulinum toxin heavy chain which works for endocytosis was injected into rat face skin and found in ipsilateral trigeminal ganglion. The labeled botulinum toxin heavy chain was not found on the contralateral side or in the only fluorescein injection. The uptake was inhibited by colchicine treatment, which blocks axonal transport. Intradermal injection of botulinum toxin alleviates infraorbital nerve constriction induced thermal hyperalgesia in an operant assay. Direct application of botulinum toxin to dorsal root ganglia reversed the sciatic nerve entrapment induced decreases in withdrawal thresholds.
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A multifunctional implant which can achieve the site-specific tissue regeneration
Grant number：22390366 2010.04 - 2014.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
MAEKAWA Kenji, HAYAKAWA Satoshi, SONOYAMA Wataru, KUBOKI Takuo, ITOH Yoshihiro
Grant amount：\19240000 （ Direct expense: \14800000 、 Indirect expense：\4440000 ）
Our previous technique for apatite deposition onto the titanium surface after insertion in human body, can be only applied to the pure titanium surface. However, in order to apply this surface modification technique to clinically used implants, improvement of the technique is necessary, because all the commercially available titanium implants are made from titanium alloy. For this purpose, we developed liquid phase deposition (LPD) technique, which can induce the apatite formation onto the titanium alloy surface after insertion in human body. We found that rat bone marrow stromal cells (rBMSC) can be attached to this modified titanium alloy surface (treated by LPD technique) and the osseogenesis of rBMSC tended to be accelerated. Recently, the investigation of the bioactivity of this surface modification technique using rat model is still ongoing.
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高脂血症治療薬；スタチンを応用した象牙質形成促進作用を持つ新規覆髄材の開発
Grant number：22592150 2010.04 - 2013.03
日本学術振興会 科学研究費助成事業 基盤研究(C) 基盤研究(C)
岡本 洋介, 窪木 拓男, 松香 芳三, 園山 亘, 大野 充昭
Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）
1.in vitroでのスタチンの歯髄幹綱胞における作用機序の検討
スタチンはメバロン酸経路の上流にあるHMG-CoA還元酵素を抑制しコレステロール産生の抑制することが報告されている。歯髄幹細胞(Dental Pulp Stem Cell : DPSC)でも同様の作用機序であるか検討するため,HMG-CoAの下流に位置するメバロン酸を用いた。培地にスタチン1μMとメバロン酸1mMの濃度で同時に添加し,MTS法で細胞増殖に与える影響を検討した。その結果,5日目にスタチン単独での細胞増殖抑制効果が消失していることを確認した。
またスタチンはメバロン酸経路の中間産物の抑制により,Rho経路を介し細胞周期をG1/S期で停止させることが報告されている。そこで細胞周期に与える影響を検討するため,スタチン1μM添加し3日間培養したDPSCをPIにて染色後,FACSを用い解析を行った。その結果,G0/G1期への集積像およびG2/M期ピークの減弱が観察された。以上の結果よりDPSCにおけるスタチンの作用はメバロン酸-Rho経路を介していることが示唆された。
2,イヌを用いた覆髄モデルの作製
本研究の臨床モデルは,歯髄に近接したカリエスが考えられる。そこで本研究ではビーグル犬(1歳齢)の犬歯を用い覆髄モデルを作製した。歯の遠心面がら近心に向け歯科用5倍速エンジンで窩洞の形成を行い,通常の歯科用覆髄剤を用い覆髄処置を行い,歯科用セメントを用い窩洞の充填を行った。1か月後に組織を回収し,通法に従い組織標本を作製した。その結果,安定して歯髄に近接した窩洞を形成できていることが確認された。
次に,このイヌ覆髄モデルを用い,スタチンの象牙質形成効果を検討した。つまり,スタチン2mMならびにPBSを各10μlを含むコラーゲンスポンジを覆髄剤として窩洞内に設置し,歯科用セメントにて充填した。1か月後に組織を回収し,組織標本を作製しHE染色を行なった結果,2mMのスタチンに有意な象牙質形成促進作用は認められなかった。 -
分子イメージングとバイオマーカー探索による慢性筋痛の局所病態解析
Grant number：22592151 2010 - 2012
日本学術振興会 科学研究費助成事業 基盤研究(C) 基盤研究(C)
小野 剛, 前川 賢治, 水口 一, 松香 芳三, 窪木 拓男
Grant amount：\2990000 （ Direct expense: \2300000 、 Indirect expense：\690000 ）
我々は,以前,近赤外線分光法を用いて慢性筋痛を訴える被験者の有痛筋組織内では,筋作業や交感神経活動亢進時の筋組織内の血管拡張機能が低下している所見を得た.さらに分子イメージング技術であるPositron emission tomography (PET)を用いて,筋組織のエネルギー源であるグルコースの取り込み量を僧帽筋に慢性筋痛を訴える被験者の僧帽筋と,非筋痛者の僧帽筋内とで比較した結果,筋痛者の僧帽筋組織内のグルコース取り込み量が非筋痛者のそれに比較して有意に抑制されることを明らかとした.これらの知見から更に慢性筋痛の病態を明らかとすることを目的に,筋組織内代謝と組織内血流の相互関係に着目した.相互関係を明らかとするためには,グルコース代謝の指標となる18F-FDGと,血流の指標となる150の筋組織内取り込み量をPETでダイレクトに測定することが有効と考え,150ガスをプローブとして実験に用いる手法の確立を目指して予備的検討を行っている.その一方で,150ガスを用いた血流動態評価が技術的な問題等で困難な場合に備え,血流の絶対量が測定可能な近赤外線分光計(オメガモニターBOM-L1 TR W)を用いて測定する血流動態測定の予備的検討も同時進行させている.加えて,最近,PETを用いた実験的研究で虚血のマーカーとして最近着目されている64Cu-ATSMを研究に用いることが可能かどうかも含めて検討中である.さらに,動物を対象としてPETを用いた基礎研究を開始することも考慮にいれ,理研分子イメージングセンターの研究者にコンタクトを取り準備を開始した.採択決定が11月となり,今年度の実質的な研究期間が3ヶ月と短かったため,実際の研究データの採取は来年度行う予定である
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インプラント周囲炎の早期診断ならびに新規治療法の開発
Grant number：21592451 2009 - 2011
日本学術振興会 科学研究費助成事業 基盤研究(C) 基盤研究(C)
山崎 聖也, 窪木 拓男, 荒川 光, 小野 剛
Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）
本研究の目的はインプラント周囲の炎症を未然に察知するためにインプラント周囲の炎症性歯肉を採取し特異的な生物学的マーカーを同定することである.昨年度に引き続き,当科で口腔インプラント治療を行った患者の中でどれだけの患者がインプラント周囲炎によりインプラントを喪失しているのかを把握する目的で,これまでに当院で口腔インプラント治療を行った患者のデータベースの整理を行った.過去15年間に当科にて口腔インプラント治療を行った全患者は453名であった,これらの患者に埋入されているインプラント体1本1本について追跡調査をおこないインプラント周囲炎の発症頻度ならびにインプラント周囲に炎症を引き起こすリスクファクターについて調査した.また,インプラント周囲に特異的に炎症が起こるのか(隣在歯から炎症が波及しているのではないか)を確認するためにインプラントの隣在歯に起こるトラブルの詳細を同時に調査した.
《方法》
1.1990年2月から2007年3月までの間に当科にて口腔インプラント治療を受けた全患者393人1062本の中でオッセオインテグレーションが獲得されたものが721本であった.これらのインプラント体を対象に多変量解析による生存分析をおこなった
2.多数歯の遊離端欠損患者に対して,インプラント群と可撤性部分床義歯群を選別し,欠損の隣在歯におこる炎症に起因するトラブルの発生を生存分析を用いて比較した
《結果》
1.インプラント体の10年累積生存率は94%であり.10本のインプラント体が除去に至っていた.インプラント体が除去に至るリスク要因は上部構造が術者可撤式である事と喫煙習慣である事が明らかとなった
2.インプラントと可撤性部分床義歯では欠損部の隣在歯におけるトラブルの発生率は有意に可撤性部分床義歯の方が高かった
今後はこれらの結果をふまえてインプラント体を除去するに至ったインプラント周囲炎をもった患者のインプラント体周囲歯肉からインプラント周囲に起こる炎症の特異的なマーカーを具体的に調査していく予定である -
VALIDITY OF PROSTHETIC CLINICAL GUIDELINE DEVELOPED ON THE BASIS OF TREATMENT DIFFICULTY INDICES
Grant number：21249092 2009 - 2011
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A) Grant-in-Aid for Scientific Research (A)
HIRAI Toshihiro, SASAKI Keiichi, SATO Yuji, ISHIBASHI Kanji, KUBOKI Takuo, BABA Kazuyoshi, HIDESHIMA Masayuki, KOBAYASHI Hiroshi, SAKURAI Kaoru, MASUMI Shinichi, KOSHINO Hisashi, AITA Hideki, KIMURA Aya, KONO Mai, KOYAMA Shigeto, KITAGAWA Noboru, TANABE Norimasa, TUKASAKI Hiroaki, WAKABAYASHI Noriyuki, RYU Masahiro, KAWANO Toshihiro
Grant amount：\46150000 （ Direct expense: \35500000 、 Indirect expense：\10650000 ）
The purpose of this study was to develop the prosthodontic clinical guideline based on treatment difficulty indices. A multi-centered epidemiological study showed the newly developed multi-axis assessment protocol was useful and reliable to estimate the level of difficulty in treating patients who needed prosthodontic care. The results suggest that the established evidence-based clinical guideline is expected to have a significant contribution to the practice of qualified prosthodontic treatment with sufficient safety and efficacy.
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Grant number：20592267 2008 - 2010
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
KANYAMA Manabu, KUBOKI Takuo, SONOYAMA Wataru, KATAOKA Ken
Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）
In this study, we isolated human dental follicle epithelial (DFE) cells that were different from gingival epithelial (GE) cells in terms of their gene expression profiles and proliferative capacity. Furthermore, DFE cells were revealed to be putative amelogenic cells based on their gene expression of an ameloblast marker, amelogenin. We found that a direct contact between DFE and dental papilla mesenchymal (DPM) cells increased an amelogenin expression in DFE cells, suggesting transmembrane signaling from the DPM cells played some pivotal roles for DFE cells to enter into the ameloblast lineage. More importantly, this increase was remarkable when DFE cells were cultured with DPM cells in comparison to DFM cells. We confirmed that DPM cells expressed dentin sialophosphoprotein (DSPP), one of odontoblast markers, but DFM cells did not. Therefore, this DPM cells-driven DFE cells differentiation might be a reproduction of epithelial - mesenchymal interaction, found in tooth generation. However, the underlying mechanisms of this induced differentiation of DFE cells were not cleared. Much more signaling works are required to elucidate epithelial - mesenchymal interaction in human tooth generation. Novel human amelogenic cells, DFE cells, might be useful tool for such kind of signaling works.
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Grant number：20592264 2008 - 2010
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
ARAKAWA Hikaru, KUBOKI Takuo, MATSUKA Yoshizo, KANYAMA Manabu, YAMAZAKI Seiya, KIMURA Aya, NODA Kinji, YAMAMOTO Michiyo
Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）
The realities that it becomes impossible for the elderly patients with dental implants to respond to the recall because of the change in the general status, especially the dementia and the circulatory system disease were clarified. Moreover, healthy elderly patients also are holding uneasiness in the maintenance method and the prognosis of the dental implants. We dentists should do the information presentation concerning the prognosis, and the reconsideration of a long-term caring plan to stare at the patient's aging is requested
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A multi-center study on prosthetic rehabilitation for Shortened Dental Arch
Grant number：20249077 2008 - 2010
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A) Grant-in-Aid for Scientific Research (A)
IGARASHI Yoshimasa, SASAKI Keiich, KOYANO Kiyoshi, KUBOKI Takuo, MAEDA Yoshinobu, BABA Kazuyoshi, AKAGAWA Yasumasa, KASUGAI Shouhei, FUEKI Kenji, KOYAMA Shigeto, TUKASAKI Hiroaki, IKEBE Kazunori, OGINO Youichirou, KORETAKE Katsunori, YOSHIDA Eiko, KONDO Hisatomo, KURODA Shinji, GARRETT Neal R
Grant amount：\34060000 （ Direct expense: \26200000 、 Indirect expense：\7860000 ）
The aim of this study was to investigate efficacy of prosthetic rehabilitation for shortened dental arch. Oral health-related quality of life and masticatory function were evaluated in patients with shortened dental arch before and after prosthetic treatments and in patients without treatment. Oral health-related quality of life and masticatory function were impaired with increase of missing posterior teeth, and they were improved after prosthetic treatment, suggesting that prosthetic rehabilitation for shortened dental arch is effective.
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Development of the basic technology for tooth regenerative therapy system
Grant number：20249078 2008 - 2010
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A) Grant-in-Aid for Scientific Research (A)
TSUJI Takashi, KUBOLKI Takuo, KASUGAI Shohei, TOMOOKA Yasuhiro, YAMAMOTO Teruko, SONOYAMA Wataru, SAITO Masahiro
Grant amount：\48620000 （ Direct expense: \37400000 、 Indirect expense：\11220000 ）
In current research on whole-tooth regenerative therapy, a basic strategy is being pursued in which a bioengineered tooth germ is induced to develop into a fully functional tooth. We developed a three-dimensional organ-germ culture method for the reconstitution a bioengineered organ germ. We successfully demonstrated that our bioengineered tooth germ could develop a fully functioning tooth, which has hardness for masticatory potential, the functional responsibility against a mechanical stress, and perceptive potentials of neural fibers. Furthermore, we demonstrated a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. These results showed that the bioengineered tooth germ and mature tooth unit could regenerate a fully functioning tooth and an organ replacement regenerative therapy might be feasible.