Faculty Profiles - KUBOKI Takuo

Can prosthodontic treatment improve mortality in various life stages?

Takuo Kuboki, Kenji Maekawa

Annals of Japan Prosthodontic Society 13 ( 2 ) 117 - 125 2021

これで自信をもって取り組める前歯部インプラント治療診断から埋入、補綴まで Step by Stepでわかる成功のポイント(Step 2)外科のポイント(1)

岩田光弘, 窪木拓男

日本歯科評論 80 ( 12 ) 93 - 102 2020.12

IMPLANT THERAPY これで自信をもって取り組める前歯部インプラント治療診断から埋入、補綴までStep by Stepでわかる成功のポイント(Step 1) 診査・診断のポイント

岩田光弘, 窪木拓男

日本歯科評論 80 ( 11 ) 71 - 80 2020.11

Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model. International journal

Kyaw Thu Aung, Kentaro Akiyama, Masayoshi Kunitomo, Aung Ye Mun, Ikue Tosa, Ha Thi Thu Nguyen, Jiewen Zhang, Teisaku Kohno, Mitsuaki Ono, Emilio Satoshi Hara, Takuo Kuboki

International journal of molecular sciences 21 ( 21 ) 2020.10

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI

Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated β galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.

DOI： 10.3390/ijms21218103

Distinct Osteogenic Potentials of BMP-2 and FGF-2 in Extramedullary and Medullary Microenvironments. International journal

Shuji Nosho, Ikue Tosa, Mitsuaki Ono, Emilio Satoshi Hara, Kei Ishibashi, Akihiro Mikai, Yukie Tanaka, Aya Kimura-Ono, Taishi Komori, Kenji Maekawa, Takuo Kuboki, Toshitaka Oohashi

International journal of molecular sciences 21 ( 21 ) 2020.10

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI

Bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2) have been regarded as the major cytokines promoting bone formation, however, several studies have reported unexpected results with failure of bone formation or bone resorption of these growth factors. In this study, BMP-2 and FGF-2 adsorbed into atellocollagen sponges were transplanted into bone defects in the bone marrow-scarce calvaria (extramedullary environment) and bone marrow-abundant femur (medullary environment) for analysis of their in vivo effects not only on osteoblasts, osteoclasts but also on bone marrow cells. The results showed that BMP-2 induced high bone formation in the bone marrow-scarce calvaria, but induced bone resorption in the bone marrow-abundant femurs. On the other hand, FGF-2 showed opposite effects compared to those of BMP-2. Analysis of cellular dynamics revealed numerous osteoblasts and osteoclasts present in the newly-formed bone induced by BMP-2 in calvaria, but none were seen in either control or FGF-2-transplanted groups. On the other hand, in the femur, numerous osteoclasts were observed in the vicinity of the BMP-2 pellet, while a great number of osteoblasts were seen near the FGF-2 pellets or in the control group. Of note, FCM analysis showed that both BMP-2 and FGF-2 administrated in the femur did not significantly affect the hematopoietic cell population, indicating a relatively safe application of the two growth factors. Together, these results indicate that BMP-2 could be suitable for application in extramedullary bone regeneration, whereas FGF-2 could be suitable for application in medullary bone regeneration.

DOI： 10.3390/ijms21217967

【「高齢者の食べることを支援するIPE・IPWについて」】介護保険施設、在宅における多職種ミールラウンドや口腔栄養関連サービスをいかに根付かせるかミールラウンドとそれに基づくカンファレンスを多職種連携スモールグループディスカッション教育で模倣した試み

窪木拓男, 縄稚久美子, 水口真実, 前田あずさ, 中村幸伸, 日笠晴香, 佐川敬一朗, 田代晴基, 戸原雄, 高橋賢晃, 菊谷武

保健医療福祉連携 13 ( 2 ) 119 - 124 2020.10

BMP-2/β-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model. International journal

Akihiro Mikai, Mitsuaki Ono, Ikue Tosa, Ha Thi Thu Nguyen, Emilio Satoshi Hara, Shuji Nosho, Aya Kimura-Ono, Kumiko Nawachi, Takeshi Takarada, Takuo Kuboki, Toshitaka Oohashi

International journal of molecular sciences 21 ( 19 ) 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI

Medication-related osteonecrosis of the jaw (MRONJ) is a severe pathological condition associated mainly with the long-term administration of bone resorption inhibitors, which are known to induce suppression of osteoclast activity and bone remodeling. Bone Morphogenetic Protein (BMP)-2 is known to be a strong inducer of bone remodeling, by directly regulating osteoblast differentiation and osteoclast activity. This study aimed to evaluate the effects of BMP-2 adsorbed onto beta-tricalcium phosphate (β-TCP), which is an osteoinductive bioceramic material and allows space retention, on the prevention and treatment of MRONJ in mice. Tooth extraction was performed after 3 weeks of zoledronate (ZA) and cyclophosphamide (CY) administration. For prevention studies, BMP-2/β-TCP was transplanted immediately after tooth extraction, and the mice were administered ZA and CY for an additional 4 weeks. The results showed that while the tooth extraction socket was mainly filled with a sparse tissue in the control group, bone formation was observed at the apex of the tooth extraction socket and was filled with a dense connective tissue rich in cellular components in the BMP-2/β-TCP transplanted group. For treatment studies, BMP-2/β-TCP was transplanted 2 weeks after tooth extraction, and bone formation was followed up for the subsequent 4 weeks under ZA and CY suspension. The results showed that although the tooth extraction socket was mainly filled with soft tissue in the control group, transplantation of BMP-2/β-TCP could significantly accelerate bone formation, as shown by immunohistochemical analysis for osteopontin, and reduce the bone necrosis in tooth extraction sockets. These data suggest that the combination of BMP-2/β-TCP could become a suitable therapy for the management of MRONJ.

DOI： 10.3390/ijms21197028

Safe and Predictable Hard Tissue Augmentation Modalities and Their Proper Use

小田師巳, 小田師巳, 園山亘, 園山亘, 窪木拓男

日本口腔インプラント学会誌 33 ( 3 ) 266 - 274 2020.9

AIによる医療革命に備える歯科界はAIの進歩にどのように対応するのか?

窪木拓男, 松岡由幸, 山口高平, 井汲憲治

The Quintessence 39 ( 7 ) 1666 - 1673 2020.7

Number of functional teeth more strongly predicts all-cause mortality than number of present teeth in Japanese older adults. Reviewed

Kenji Maekawa, Tomoko Ikeuchi, Shoji Shinkai, Hirohiko Hirano, Masahiro Ryu, Katsushi Tamaki, Hirofumi Yatani, Takuo Kuboki, Aya Kimura-Ono, Takeshi Kikutani, Takashi Suganuma, Yasunori Ayukawa, Tomoya Gonda, Toru Ogawa, Masanori Fujisawa, Shoichi Ishigaki, Yutaka Watanabe, Akihiko Kitamura, Yu Taniguchi, Yoshinori Fujiwara, Ayako Edahiro, Yuki Ohara, Junichi Furuya, Junko Nakajima, Kento Umeki, Kentaro Igarashi, Yasuhiro Horibe, Yoshihiro Kugimiya, Yasuhiko Kawai, Hideo Matsumura, Tetsuo Ichikawa, Shuji Ohkawa

Geriatrics & gerontology international 20 ( 6 ) 607 - 614 2020.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

AIM: Previous studies on the association between intraoral conditions and mortality in community-dwelling older individuals reported that fewer present teeth (PT) are significant risk factors for mortality. However, how the number of PT relative to the number of functional teeth (FT), including both present and rehabilitated teeth, influences mortality has not been investigated fully. This study examined the impact of the number of FT on mortality among community-dwelling Japanese older adults. METHODS: This study was a retrospective, observational and population-based follow-up study, which examined 1188 older individuals who participated in an annual geriatric health examination from 2009 to 2015. The average follow-up period was 1697.0 ± 774.5 days. The primary outcome was all-cause mortality at follow-up. The numbers of PT and FT of each participant were counted during an oral examination. In addition, demographics, clinical variables, blood nutrient markers, physical functions and perceived masticatory function were measured. RESULTS: Kaplan-Meier analysis, followed by a log-rank test, revealed that fewer PT (P < 0.001) and FT (P = 0.002) were significantly associated with a reduced survival rate. Cox's proportional hazard analysis indicated that the number of FT, but not the number of PT, was a significant independent mortality risk factor after adjusting for demographics, clinical variables, nutrient markers and physical functioning (P = 0.036, hazard ratio: 2.089). CONCLUSIONS: Current results suggest that the number of FT more strongly predicts all-cause mortality than the number of PT among community-dwelling older adults. Further studies are necessary to consider the confounding of socioeconomic status and disability status. Geriatr Gerontol Int 2020; ••: ••-••.

DOI： 10.1111/ggi.13911

A Re-evaluation of Implant Treatment Based on Causes of Missing Teeth : Implant Treatment for Patients Who Have Lost Teeth Due to Severe Periodontitis

岩田光弘, 荒川光, 中川晋輔, 窪木拓男

日本口腔インプラント学会誌 33 ( 2 ) 134 - 141 2020.6

Association of masticatory muscle activity with sleep arousal and other concomitant movements during sleep. Reviewed International journal

Haruna Miki, Hajime Minakuchi, Mayu Miyagi, Emilio Satoshi Hara, Shuji Shigemoto, Yoshitaka Suzuki, Kenji Maekawa, Yoshizo Matsuka, Glenn T Clark, Takuo Kuboki

Journal of oral rehabilitation 47 ( 3 ) 281 - 288 2020.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

OBJECTIVE: This study aims to verify the associations among sleep bruxism (SB), sleep arousal (SA) and concurrent body movements. MATERIAL AND METHODS: Subjects underwent a standard overnight polysomnography test and audio-video recordings. Sleep quality was evaluated according to the Rechtschaffen and Kales criteria, while SA was determined as per the American Sleep Disorders Association criteria. Analyses were performed by an external institution after masking of the subjects' information. SB was assessed based on the presence/absence of rhythmic masticatory muscle activity (RMMA) episodes, which were identified by using electromyography of the masseter muscle. The observed simultaneous movements included lower leg movement (LLM), swallowing, face scratching, head movement, body movement, eye blinking, coughing, licking, sighing, body scratching, lip sucking, somniloquy and yawning. The LLM was determined visually, as well as through an increase in the tibialis electromyogram signal. Other movements were visually assessed using audio-video recordings. The incidences of all the simultaneous movements were compared between RMMA with intercurrent SA (SAwRMMA; RMMA episode derived from a masseter electromyogram showing more than 10% of maximum voluntary contraction) and SA without RMMA (SAw/oRMMA). RESULTS: Fourteen subjects were included in this study (females/males: 4/10, mean age: 31.5 ± 5.7 years). Among these, LLM, swallowing, body movement, licking, body scratching and lip sucking were frequently observed in SAwRMMA episodes than in SAw/oRMMA episodes, significantly. However, the non-specific simultaneous movements were higher observed in SAw/oRMMA episodes than that in SAwRMMA. CONCLUSION: Our results suggest that SB is concurrently activated with LLM in relation to arousal.

DOI： 10.1111/joor.12913

Vibratory splint therapy for decreasing sleep clenching: A pilot study. Reviewed International journal

Emilio Satoshi Hara, Andrea Lusvarghi Witzel, Hajime Minakuchi, Carlos Eduardo de Pitta, Rosane Tronquin Gallo, Masahiro Okada, Takuya Matsumoto, Takuo Kuboki, Marcelo Costa Bolzan

Cranio : the journal of craniomandibular practice 38 ( 1 ) 15 - 21 2020.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Informa {UK} Limited

OBJECTIVE: To estimate the effect of a vibratory splint (VibS) in reducing sleep clenching (SC) and TMD pain. METHODS: Target sample was consecutive 19 TMD patients attending the Orofacial Pain Clinic at FFO-FOUSP. Patients used the VibS or acrylic occlusal splint (OS) as control for 14 days. Outcome variables were SC frequency and pain, assessed by a portable electromyography detector-analyzer (BiteStrip™) and 100 mm VAS, respectively. Statistical analyses were performed with two-way repeated measures ANOVA, and analysis of covariance (ANCOVA). RESULTS: VibS promoted a marked decrease, whereas acrylic OS increased SC frequency after two weeks of use. Due to a significant difference in initial VAS levels between VibS and control group, the effect of the two splints on TMD pain could not be clearly estimated. CONCLUSION: The results suggested that VibS can potentially be used to reduce SC frequency, although further studies with larger sample size are necessary to confirm these findings.

DOI： 10.1080/08869634.2018.1488652

Full Digital Workflow for Use of a Scanbody to Accurately Transfer Morphology From Provisional to Final Implant-Supported Fixed Restoration. International journal

Takuya Mino, Yoko Kurosaki, Kenji Maekawa, Kana Tokumoto, Koji Izumi, Akihiro Ueda, Aya Kimura-Ono, Takuo Kuboki

The Journal of oral implantology 45 ( 6 ) 494 - 498 2019.12

Postnatal Runx2 deletion causes age-related changes in bone.

Ikue Tosa, Daisuke Yamada, Shunpei Tsukamoto, Kenji Kawabe, Takeshi Takarada, Mitsuaki Ono, Toshitaka Oohashi, Takuo Kuboki

JOURNAL OF BONE AND MINERAL RESEARCH 34 219 - 219 2019.12

Relationship between oral environment and development of pneumonia and acute viral respiratory infection in dependent older individuals.

Haruki Tashiro, Takeshi Kikutani, Fumiyo Tamura, Noriaki Takahashi, Takashi Tohara, Kumiko Nawachi, Kenji Maekawa, Takuo Kuboki

Geriatrics & gerontology international 19 ( 11 ) 1136 - 1140 2019.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

AIM: The importance of oral care has been recognized for the prevention of airway infections in older individuals who require long-term care. The present prospective cohort study was carried out a decade ago to identify risk factors with numerous intraoral conditions as possible predictors involved in the onset of pneumonia and acute viral respiratory infection (AVRI) in older people requiring long-term care during a 6-month follow-up period (including winter). METHODS: This study included 1785 older individuals residing in 31 long-term care facilities in which dental hygienists were involved in instruction on daily oral care. Primary end-points were development of pneumonia and AVRI during the 6-month follow-up period. Several factors related to each participant's general condition, oral environment, swallowing function and vaccinations (or lack thereof) were evaluated by calibrated dentists and dental hygienists before the study onset. RESULTS: During the 6-month follow-up period, 74 participants (4.1%) developed pneumonia, and 28 participants (1.6%) developed AVRI. Cox proportional hazard analysis showed that poor nutritional status and the presence of dysphagia were significant risk factors for pneumonia onset. The presence of dry mouth and halitosis were significant risk factors for AVRI. CONCLUSIONS: This prospective multicenter cohort study identified poor nutritional status and dysphagia as independent risk factors for the development of pneumonia, and dry mouth and halitosis as independent risk factors for the development of AVRI in older people who require long-term care and who routinely receive professional oral care. Geriatr Gerontol Int 2019; 19: 1136-1140.

DOI： 10.1111/ggi.13784

Secondary Publication 補綴歯科治療の難易度を測定するプロトコルの妥当性の検討 (公社)日本補綴歯科学会による多施設臨床研究

窪木拓男, 市川哲雄, 馬場一美, 藤澤政紀, 佐藤博信, 會田英紀, 小山重人, 秀島雅之, 佐藤裕二, 和気裕之, 大野彩, 木村, 永尾寛, 上田順加, 平, 玉置勝司, 貞森紳丞, 津賀一弘, 西恭宏, 澤瀬隆, 越野寿, 鱒見進一, 櫻井薫, 石橋寛二, 大山喬史, 赤川安正, 平井敏博, 佐々木啓一, 古谷野潔, 矢谷博文, 松村英雄

日本補綴歯科学会誌 11 ( 4 ) 355 - 375 2019.10

Language：Japanese Publisher：(公社)日本補綴歯科学会

目的:日本補綴歯科学会は、補綴歯科治療を必要とする患者の複雑な多様性を評価し、それをもとに難易度分類を行うことを目的に「補綴歯科治療の難易度を測定する多軸診断プロトコル」を作成し、すでに臨床上十分な信頼性を示すことを確認した。本研究では多施設臨床追跡研究により本プロトコルの妥当性を検討した。方法:新たに作成した多軸診断プロトコルは、口腔内の状態、身体社会的状態、口腔関連QOL(OHIP-J54)、精神心理学的状態の4つの診断軸からなる。それぞれグレード0(易しい)から3(難しい)の4段階評価を行う。日本補綴歯科学会の認定研修施設である大学病院補綴科9施設で、歯質もしくは歯列欠損に対し補綴歯科治療が必要と判断された初診患者を連続サンプリングした。補綴歯科治療前に、本プロトコルを用いて難易度評価を行った。そして補綴歯科治療後に、治療に要した時間、医療費などの医療資源および口腔関連QOL評価を行った。本プロトコルの構成概念妥当性は、治療前の術者の主観による難易度評価と、本プロトコルの各軸の難易度の相関を求め検討した。予測妥当性は、総医療費、総治療時間、治療前後の口腔関連QOL変化量をサロゲートエンドポイントとして用い、本プロトコルの4つの診断軸の難易度を統合した総合難易度との相関を求めた。結果と考察:口腔内の状態(Axis I)、身体社会的状態(Axis II)、口腔関連QOL(Axis III)と治療前の術者の主観による難易度評価は、有意な正の相関を示した。一方、精神心理学的状態(Axis IV)と治療前の術者の主観による難易度評価には相関が認められなかった。術前に本プロトコルで評価した患者の総合難易度は、治療の難易度とよく関連すると考えられるサロゲートエンドポイント(総治療費、総治療時間、口腔関連QOL改善量)のいずれとも有意に相関した。口腔内状況別にこの関係を精査すると、術前の総合難易度評価は、全部歯列欠損症例や部分歯列欠損症例においては、これらのサロゲートエンドポイントの一部と有意に相関が認められたが、全部歯列欠損と部分歯列欠損の混合症例や歯の問題の症例においては、それらのサンプルサイズが小さいこともあり有意差が認められなかった。結論:補綴歯科治療の難易度を初めて多軸診断することに成功した本プロトコルの総合難易度評価は、全部歯列欠損症例や部分歯列欠損においては、臨床使用上十分な予測妥当性を示すことがわかった。(著者抄録)

DOI： 10.2186/ajps.11.355

CiNii Article

CiNii Books

【二次出版】Secondary Publication 補綴歯科治療の難易度を測定するプロトコルの妥当性の検討 (公社)日本補綴歯科学会による多施設臨床研究

Other Link： http://id.ndl.go.jp/bib/030070171

窪木拓男, 市川哲雄, 馬場一美, 藤澤政紀, 佐藤博信, 會田英紀, 小山重人, 秀島雅之, 佐藤裕二, 和気裕之, 大野彩[木村], 永尾寛, 上田順加[小平], 玉置勝司, 貞森紳丞, 津賀一弘, 西恭宏, 澤瀬隆, 越野寿, 鱒見進一, 櫻井薫, 石橋寛二, 大山喬史, 赤川安正, 平井敏博, 佐々木啓一, 古谷野潔, 矢谷博文, 松村英雄

日本補綴歯科学会誌 11 ( 4 ) 355 - 375 2019.10

Language：Japanese Publisher：(公社)日本補綴歯科学会

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J05334&link_issn=&doc_id=20191101190011&doc_link_id=%2Fdv5proso%2F2019%2F001104%2F013%2F0355-0375%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdv5proso%2F2019%2F001104%2F013%2F0355-0375%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Type XVIII Collagen Modulates Keratohyalin Granule Formation and Keratinization in Oral Mucosa. Reviewed International journal

Ha Thi Thu Nguyen, Mitsuaki Ono, Emilio Satoshi Hara, Taishi Komori, Midori Edamatsu, Tomoko Yonezawa, Aya Kimura-Ono, Kenji Maekawa, Takuo Kuboki, Toshitaka Oohashi

International journal of molecular sciences 20 ( 19 ) 2019.9

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI

Epithelial keratinization involves complex cellular modifications that provide protection against pathogens and chemical and mechanical injuries. In the oral cavity, keratinized mucosa is also crucial to maintain healthy periodontal or peri-implant tissues. In this study, we investigated the roles of type XVIII collagen, a collagen-glycosaminoglycan featuring an extracellular matrix component present in the basement membrane, in oral mucosal keratinization. Histological analysis of keratinized and non-keratinized oral mucosa showed that type XVIII collagen was highly expressed in keratinized mucosa. Additionally, a 3D culture system using human squamous carcinoma cells (TR146) was used to evaluate and correlate the changes in the expression of type XVIII collagen gene, COL18A1, and epithelial keratinization-related markers, e.g., keratin 1 (KRT1) and 10 (KRT10). The results showed that the increase in COL18A1 expression followed the increase in KRT1 and KRT10 mRNA levels. Additionally, loss-of-function analyses using silencing RNA targeting COL18A1 mRNA and a Col18-knockout (KO) mouse revealed that the absence of type XVIII collagen induces a dramatic decrease in KRT10 expression as well as in the number and size of keratohyalin granules. Together, the results of this study demonstrate the importance of type XVIII collagen in oral mucosal keratinization.

DOI： 10.3390/ijms20194739