Faculty Profiles - KUBOKI Takuo

Papers - KUBOKI Takuo

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BMP-2 generates a functional bone marrow niche by inducing the differentiation of local mesenchymal cells into CAR cells

Mitsuaki Ono, Ikue Tosa, Anh Tuan Dang, Ziyi Wang, Maiko Kimura, Wakana Kitagawa, Kei Ishibashi, Hang Thuy Do, Kun Zhao, Emilio Satoshi Hara, Noboru Asada, Takashi Nagasawa, Toshitaka Oohashi, Naoya Ohara, Takuo Kuboki

Blood Advances 2025.3

Publishing type：Research paper (scientific journal) Publisher：American Society of Hematology

Ectopic bone marrow (eBM) holds tremendous potential as an artificial organ, serving not only in stem cell transplantation therapies but also as a controlled experimental system for analyzing cellular dynamics and interactions between cells and the matrix during the formation, maintenance, and aging of bone marrow (BM). Although bone morphogenetic protein (BMP)-2 has been reported to induce eBM formation, it remains unproven whether BMP-2 induced eBM (BMP-eBM) can provide a functional BM niche that is comparable to native BM in long bones (LB-BM). In this study, through the use of single-cell RNA sequencing and transplantation models, we demonstrate for the first time that BMP-eBM displays a microstructure, cellular composition, and functional hematopoiesis similar to LB-BM. BMP-eBM establishes an optimized microenvironment capable of supporting hematopoietic stem cells (HSCs) and CXC-chemokine-ligand-12 (CXCL12)-abundant reticular (CAR) cells, which are critical components of the BM niche. Significantly, BMP-eBM was able to restore survival in irradiated mice. Through parabiosis and cell transplantation experiments, we identified that in situ adipose tissue-derived CD51highCxcl12-GFP- cells are the principal source of CAR cells within BMP-eBM. Furthermore, BMP-eBM can be isolated and, after preconditioning, re-transplanted as an independent, functional hematopoietic organ. In conclusion, our study confirms that BMP-eBM functions effectively as a hematopoietic organ, capable of supporting and maintaining a functional BM niche. These findings underscore BMP-2 as a crucial molecule for eBM generation and suggest its potential for addressing BM-related diseases and for use as a platform for in vitro and ex vivo biomedical applications.

DOI： 10.1182/bloodadvances.2024014062

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Optimizing β-TCP with E-rhBMP-2-infused fibrin for vertical bone regeneration in a mouse calvarium model

Kun Zhao, Mitsuaki Ono, Xindi Mu, Ziyi Wang, Shichao Xie, Tomoko Yonezawa, Masahiro Okada, Takuya Matsumoto, Takuo Kuboki, Toshitaka Oohashi

Regenerative Biomaterials 12 2025.1

Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

Abstract

Effective reconstruction of large bone defects, particularly in thickness, remains one of the major challenges in orthopedic and dental fields. We previously produced an Escherichia coli-based industrial-scale GMP-grade recombinant human bone morphogenetic protein-2 (E-rhBMP-2) and showed that the combination of E-rhBMP-2 with beta-tricalcium phosphate (β-TCP/E-rhBMP-2) can effectively promote bone reconstruction. However, the limited mechanical strength and poor morphology retention of β-TCP granules are key points that need optimization to obtain more effective grafts and further expand its clinical applications. Therefore, we combined β-TCP/E-rhBMP-2 with fibrin gel to enhance its mechanical properties and usability for vertical bone regeneration. We investigated the mechanical properties and vertical bone regeneration effects of the materials applied, with or without fibrin containing E-rhBMP-2, in a calvarial defect model in mice. Compression tests were conducted to assess the initial stability of the materials. Scanning electron microscopy and Fourier transform infrared spectroscopy were conducted to characterize the presence of fibrin on the scaffold. After 4 and 12 weeks of implantation, micro-computed tomography and histological and immunofluorescent analyses were performed to assess the morphology and volume of the newly formed bone. The fibrin-containing groups had significantly higher initial mechanical strength and higher ability to maintain their morphology in vivo compared to the counterparts without fibrin. However, fibrin gel alone suppressed the bone formation ability of β-TCP/E-rhBMP-2 whereas the presence of high doses of E-rhBMP-2 in fibrin gel resulted in material resorption and enhanced new bone formation. In conclusion, fibrin gel significantly improved the mechanical strength and surgical manageability of the β-TCP/E-rhBMP-2 scaffold, and the addition of E-rhBMP-2 to the fibrin gel further enhanced the vertical bone regeneration and initial structural integrity of the scaffold.

DOI： 10.1093/rb/rbae144

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Other Link： https://academic.oup.com/rb/article-pdf/doi/10.1093/rb/rbae144/61841803/rbae144.pdf

Association among prosthodontic treatment, dietary diversity, and ingestible food profile in older outpatients with missing teeth

Kazuki Sakamoto, Aya Kimura-Ono, Yoko Kurosaki, Takuya Mino, Shinsuke Nakagawa, Yuji Shimomura, Kou Omori, Takaharu Higuchi, Eri Koyama, Kumiko Nawachi, Kana Tokumoto, Yuji Tsuchiyama, Tokihiro Fukutoku, Mitsuaki Ono, Takuo Kuboki

Journal of Prosthodontic Research 2025

既製NSVの改良開発(第一報) 設計と形状

庄賀春生, 宮崎文伸, 太田圭二, 松岸諒, 桑原実穂, 吉實舞, 兒玉直紀, 田中祐貴, 古西隆之, 藤田隼平, 瀬島淳一, 窪木拓男

日本口腔顎顔面技工学会会誌 24 ( 1 ) 46,51 - 52 2024.12

Implant-supported fixed prostheses with cantilever: a systematic review and meta-analysis. International journal

Yusuke Kondo, Kiyoshi Sakai, Hajime Minakuchi, Takuya Horimai, Takuo Kuboki

International journal of implant dentistry 10 ( 1 ) 57 - 57 2024.11

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

PURPOSE: This systematic review (SR) aimed to investigate whether the presence of a cantilever affects the results of implant treatment for partial edentulism, including an analysis of the anterior and posterior regions of the dental arches. METHODS: An electronic search was performed, and original articles published between 1995 and November 2023 were included. The outcomes were the implant survival rate, patient satisfaction, occurrence of mechanical complications, and marginal bone loss around the implants. Two SR members independently examined the validity of the studies, extracted evidence from the included studies, and performed risk of bias assessment, comprehensive evidence evaluation, and meta-analysis. RESULTS: Nine studies met our inclusion criteria. Implant survival rate tended to be lower in the cantilever group, and marginal bone loss tended to be higher in the cantilever group; however, there was no significant difference. There was no significant difference in patient satisfaction based on the presence or absence of a cantilever. Moreover, the incidence of mechanical complications was significantly higher in the cantilever group. According to the analysis of anterior and posterior regions, implant survival rate tended to be lower in the cantilever group of the posterior region, and marginal bone loss around the implants tended to be higher in the cantilever group of the anterior region. CONCLUSION: Implant-supported fixed prostheses with cantilevers did not negatively affect implant survival rate, marginal bone loss, or patient satisfaction. However, the incidence of mechanical complications significantly increased in the cantilever group.

DOI： 10.1186/s40729-024-00573-8

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Macrophages modulate mesenchymal stem cell function via tumor necrosis factor alpha in tooth extraction model. Reviewed International journal

Aung Ye Mun, Kentaro Akiyama, Ziyi Wang, Jiewen Zhang, Wakana Kitagawa, Teisaku Kohno, Ryuji Tagashira, Kei Ishibashi, Naoya Matsunaga, Tingling Zou, Mitsuaki Ono, Takuo Kuboki

JBMR plus 8 ( 8 ) ziae085 2024.8

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Mesenchymal stem cells (MSCs) and macrophages collaboratively contribute to bone regeneration after injury. However, detailed mechanisms underlying the interaction between MSCs and inflammatory macrophages (M1) remain unclear. A macrophage-depleted tooth extraction model was generated in 5-wk-old female C57BL/6J mice using clodronate liposome (12.5 mg/kg/mouse, intraperitoneally) or saline injection (control) before maxillary first molar extraction. Mice were sacrificed on days 1, 3, 5, 7, and 10 after tooth extraction (n = 4). Regenerated bone volume evaluation of tooth extraction socket (TES) and histochemical analysis of CD80+M1, CD206+M2 (anti-inflammatory macrophages), PDGFRα+MSC, and TNF-α+ cells were performed. In vitro, isolated MSCs with or without TNF-α stimulation (10 ng/mL, 24 h, n = 3) were bulk RNA-sequenced (RNA-Seq) to identify TNF-α stimulation-specific MSC transcriptomes. Day 7 micro-CT and HE staining revealed significantly lower mean bone volume (clodronate vs control: 0.01 mm3 vs 0.02 mm3, p<.0001) and mean percentage of regenerated bone area per total TES in clodronate group (41.97% vs 54.03%, p<.0001). Clodronate group showed significant reduction in mean number of CD80+, TNF-α+, PDGFRα+, and CD80+TNF-α+ cells on day 5 (306.5 vs 558.8, p<.0001; 280.5 vs 543.8, p<.0001; 365.0 vs 633.0, p<.0001, 29.0 vs 42.5, p<.0001), while these cells recovered significantly on day 7 (493.3 vs 396.0, p=.0004; 479.3 vs 384.5, p=.0008; 593.0 vs 473.0, p=.0010, 41.0 vs 32.5, p=.0003). RNA-Seq analysis showed that 15 genes (|log2FC| > 5.0, log2TPM > 5) after TNF-α stimulation were candidates for regulating MSC's immunomodulatory capacity. In vivo, Clec4e and Gbp6 are involved in inflammation and bone formation. Clec4e, Gbp6, and Cxcl10 knockdown increased osteogenic differentiation of MSCs in vitro. Temporal reduction followed by apparent recovery of TNF-α-producing M1 macrophages and MSCs after temporal macrophage depletion suggests that TNF-α activated MSCs during TES healing. In vitro mimicking the effect of TNF-α on MSCs indicated that there are 15 candidate MSC genes for regulation of immunomodulatory capacity.

DOI： 10.1093/jbmrpl/ziae085

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The cell membrane as biofunctional material for accelerated bone repair. Reviewed International journal

Emi Hatano, Nahid Akhter, Risa Anada, Mitsuaki Ono, Toshitaka Oohashi, Takuo Kuboki, Hiroshi Kamioka, Masahiro Okada, Takuya Matsumoto, Emilio Satoshi Hara

Acta biomaterialia 2024.7

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

The cell (plasma) membrane is enriched with numerous receptors, ligands, enzymes, and phospholipids that play important roles in cell-cell and cell-extracellular matrix interactions governing, for instance, tissue development and repair. We previously showed that plasma membrane nanofragments (PMNFs) act as nucleation sites for bone formation in vivo, and induce in vitro mineralization within 1 day. In this study, we optimized the methods for generating, isolating, and applying PMNFs as a cell-free therapeutic to expedite bone defect repair. The PMNFs were isolated from different mouse cell lines (chondrocytes, osteoblasts, and fibroblasts), pre-conditioned, lyophilized, and subsequently transplanted into 2 mm critical-sized calvarial defects in mice (n = 75). The PMNFs from chondrocytes, following a 3-day pre-incubation, significantly accelerated bone repair within 2 weeks, through a coordinated attraction of macrophages, endothelial cells, and osteoblasts to the healing site. In vitro experiments confirmed that PMNFs enhanced cell adhesion. Comparison of the PMNF efficacy with phosphatidylserine, amorphous calcium phosphate (ACP), and living cells confirmed the unique ability of PMNFs to promote accelerated bone repair. Importantly, PMNFs promoted nearly complete integration of the regenerated bone with native tissue after 6 weeks (% non-integrated bone area = 15.02), contrasting with the partial integration (% non-integrated bone area = 56.10; p < 0.01, Student's test) with transplantation of ACP. Vickers microhardness tests demonstrated that the regenerated bone after 6 weeks (30.10 ± 1.75) exhibited hardness similar to native bone (31.07 ± 2.46). In conclusion, this is the first study to demonstrate that cell membrane can be a promising cell-free material with multifaceted biofunctional properties that promote accelerated bone repair. STATEMENT OF SIGNIFICANCE.

DOI： 10.1016/j.actbio.2024.07.037

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Long-term follow-up of a patient with Parkinson's disease under nursing care after replacement of fixed implant-supported prostheses with an implant overdenture: a case report. Reviewed International journal

Kana Tokumoto, Takuya Mino, Ikue Tosa, Ko Omori, Michiyo Yamamoto, Kazuki Takaoka, Kenji Maekawa, Takuo Kuboki, Hiromitsu Kishimoto

International journal of implant dentistry 10 ( 1 ) 37 - 37 2024.7

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

BACKGROUND: In older patients with progressive neurodegeneration, replacing fixed implant-supported prostheses (FIP) with implant overdentures (IOD) has been proposed to prevent future mucosal injury and create an oral environment that is easier for caregivers to clean. However, there have been no reports on the progress after replacing FIP with IOD. In this report, we present the progress of an older patient with Parkinson's disease in whom FIP was replaced with IOD. CASE PRESENTATION: An 81-year-old male patient with Parkinson's disease presented to our outpatient clinic with bruxism and crossbites. FIPs, with five Brånemark system implants, were placed in the bilateral lower molars. The FIP was replaced with an IOD with two locator attachments to create an oral environment that was easier for caregivers to clean and allow easy recovery of masticatory function if residual teeth were fractured in the care environment. As his systemic condition deteriorated, treatment was changed from outpatient to in-home visits. During dental care visits, professional oral cleaning and denture repair were continued, and good nutritional status was maintained. However, the patient developed cholecystitis and was hospitalized. During hospitalization, gastrostomy was performed because he developed aspiration pneumonia. After discharge from the hospital, the patient remained in bed all day and could not wear an IOD, resulting in buccal mucosa ulceration due to abrasion of the locator abutment. We decided to replace the abutment with cover screws; however, not all the implants could sleep submucosally. Although regular oral cleaning was resumed, new ulcers developed even when cover screws were installed. Additionally, swelling and drainage were observed at the peri-implant mucosal site where peri-implantitis had once occurred during an outpatient visit. The patient was readmitted to the hospital for a urinary tract infection, and subsequent visits were abandoned. CONCLUSIONS: By replacing FIP with IOD in an older patient with Parkinson's disease, we addressed a barrier to caregiver-provided oral management. The removable prosthesis facilitated smooth oral care by caregivers and functional recovery in the event of trouble with residual teeth. However, it could not completely avoid the recurrence of buccal mucosal ulcers or peri-implantitis.

DOI： 10.1186/s40729-024-00557-8

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Medical-dental collaboration on an exploratory research project on the correlation between cognitive and oral function: The ECCO project. Reviewed

Kenji Fueki, Yuta Manabe, Keiichi Sasaki, Katsuhiko Kimoto, Mamoru Hashimoto, Takayuki Ueda, Kumiko Utsumi, Tomohisa Ishikawa, Kazuyoshi Baba, Manabu Ikeda, Takuo Kuboki

Journal of prosthodontic research 2024.7

Local E-rhBMP-2/β-TCP Application Rescues Osteocyte Dendritic Integrity and Reduces Microstructural Damage in Alveolar Bone Post-Extraction in MRONJ-like Mouse Model Reviewed International journal

Anh Tuan Dang, Mitsuaki Ono, Ziyi Wang, Ikue Tosa, Emilio Satoshi Hara, Akihiro Mikai, Wakana Kitagawa, Tomoko Yonezawa, Takuo Kuboki, Toshitaka Oohashi

International Journal of Molecular Sciences 25 ( 12 ) 6648 - 6648 2024.6

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.

DOI： 10.3390/ijms25126648

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Inverse genetics tracing the differentiation pathway of human chondrocytes Reviewed

H.T. Do, M. Ono, Z. Wang, W. Kitagawa, A.T. Dang, T. Yonezawa, T. Kuboki, T. Oohashi, S. Kubota

Osteoarthritis and Cartilage 2024.6

パーキンソン病患者の固定性インプラント補綴を可撤性へ置換後に介護現場でトラブルを生じた症例

徳本佳奈, 窪木拓男

日本老年歯科医学会総会・学術大会プログラム・抄録集 35回認定P - 08 2024.6

Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa Reviewed International journal

Xindi Mu, Mitsuaki Ono, Ha Thi Thu Nguyen, Ziyi Wang, Kun Zhao, Taishi Komori, Tomoko Yonezawa, Takuo Kuboki, Toshitaka Oohashi

Cells 13 ( 10 ) 807 - 807 2024.5

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

The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial–mesenchymal cell co-culture models in the air–liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, IGF2, ID1, LTBP1, LOX, SERPINE1, IL24, and MMP1 as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism.

DOI： 10.3390/cells13100807

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天然歯支台のプロビジョナルレストレーションと支台歯の三次元表面形状像を基準に理想的な最終補綴装置をデザインするデジタルワークフロー

徳本佳奈, 三野卓哉, 黒崎陽子, 和泉幸治, 仲野友人, 瀬島淳一, 大野彩, 前川賢治, 窪木拓男

日本デジタル歯科学会誌 14 ( 1 ) 81 - 81 2024.5

Associations between measured masticatory function and cognitive status: A systematic review Reviewed International journal

Kenji Maekawa, Yoshiko Motohashi, Kentaro Igarashi, Takuya Mino, Yasuhiko Kawai, Youngnam Kang, Toshihiro Hirai, Takuo Kuboki

Gerodontology 2024.3

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

Objective

This systematic review aimed to provide an overview of the most recent evidence on the association between measured masticatory function and cognitive status.

Materials and Methods

Literature and manual searches were conducted using three electronic databases (PubMed, Web of Science and CINAHL). Observational studies published between 2011 and 2021 investigating the association between masticatory function, dementia and cognitive status in adult humans were abstracted and reviewed by three reviewers. Studies that assessed participants' masticatory function using objective and subjective measurements and that individually examined its association with cognitive function were included. The included studies were divided into cross‐sectional and cohort studies, and the quality of each study was analysed using critical appraisal skills checklists. Additionally, the main conclusions and strength of the evidence were assessed for each article.

Results

A total of 21 studies (11 cross‐sectional studies that objectively evaluated masticatory function, 9 cross‐sectional studies that subjectively evaluated masticatory function and 1 prospective cohort study) were evaluated. The poorer masticatory function was associated with lower cognitive status even after adjusting for potential risk factors of dementia in four of 11 and six of nine cross‐sectional studies where the masticatory function was respectively evaluated objectively and subjectively. One prospective cohort study also demonstrated that masticatory function, as evaluated based on measurements of occlusal force, predicted cognitive decline during the follow‐up period.

Conclusion

Several studies demonstrated a positive association between masticatory function and cognitive status. However, further studies, particularly longitudinal studies, are required to determine whether the association is causal.

DOI： 10.1111/ger.12751

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Does maintaining the number of present and functional teeth benefit the longevity of life in older people requiring nursing care?: A prospective cohort study. Reviewed

Eri Koyama, Aya Kimura-Ono, Takuya Mino, Yoko Kurosaki, Kana Tokumoto, Michiyo Yamamoto, Shinsuke Nakagawa, Suguru Osaka, Kumiko Nawachi, Mami Inoue-Minakuchi, Mitsuaki Ono, Hajime Minakuchi, Kenji Maekawa, Takuo Kuboki

Journal of prosthodontic research 2024.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Prosthodontic Society

PURPOSE: This prospective cohort study examined the effects of the number of present and functional teeth on mortality among older Japanese adults requiring nursing care in an environment of comprehensive oral hygiene and nutritional management. METHODS: The study included 174 older adults (mean age: 84.4 ± 8.3 years; male/female: 49/125) in need of support or long-term care, who resided in either a local specialized healthcare facility or their own homes, and received daily oral hygiene and nutritional support at facilities in Okayama, Japan. The initial clinical oral examination along with assessment of general physical condition and nursing environment of the participants were performed in July 2013 and followed up for one year. RESULTS: All-cause mortality occurred in 28 (mean age: 88.7 ±13.4 years; male/female: 6 /22) individuals during the follow-up period. Cox proportional hazard analysis indicated that older age, low performance in activities of daily living (Barthel Index <40), and underweight status (body mass index <18.5) were significant risk factors for mortality. The number of present and functional teeth were not found to be significant risk factors for mortality. CONCLUSIONS: During the one-year follow-up period, the number of present and functional teeth did not have a significant impact on mortality among older Japanese adults requiring nursing care in a well-managed environment of oral hygiene and nutritional status.

DOI： 10.2186/jpr.JPR_D_23_00221

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Age-Related Effects on MSC Immunomodulation, Macrophage Polarization, Apoptosis, and Bone Regeneration Correlate with IL-38 Expression. Reviewed International journal

Jiewen Zhang, Kentaro Akiyama, Aung Ye Mun, Ryuji Tagashira, Tingling Zou, Naoya Matsunaga, Teisaku Kohno, Takuo Kuboki

International journal of molecular sciences 25 ( 6 ) 2024.3

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

Mesenchymal stem cells (MSCs) are known to promote tissue regeneration and suppress excessive inflammation caused by infection or trauma. Reported evidence indicates that various factors influence the expression of MSCs' endogenous immunomodulatory properties. However, the detailed interactions of MSCs with macrophages, which are key cells involved in tissue repair, and their regulatory mechanisms are not completely understood. We herein investigated how age-related immunomodulatory impairment of MSCs alters the interaction of MSCs with macrophages during bone healing using young (5-week old) and aged (50-week old) mice. To clarify the relationship between inflammatory macrophages (M1) and MSCs, their spatiotemporal localization at the bone healing site was investigated by immunostaining, and possible regulatory mechanisms were analyzed in vitro co-cultures. Histomorphometric analysis revealed an accumulation of M1 and a decrease in MSC number at the healing site in aged mice, which showed a delayed bone healing. In in vitro co-cultures, MSCs induced M1 apoptosis through cell-to-cell contact but suppressed the gene expression of pro-inflammatory cytokines by soluble factors secreted in the culture supernatant. Interestingly, interleukin 38 (Il-38) expression was up-regulated in M1 after co-culture with MSCs. IL-38 suppressed the gene expression of inflammatory cytokines in M1 and promoted the expression of genes associated with M1 polarization to anti-inflammatory macrophages (M2). IL-38 also had an inhibitory effect on M1 apoptosis. These results suggest that MSCs may induce M1 apoptosis, suppress inflammatory cytokine production by M1, and induce their polarization toward M2. Nevertheless, in aged conditions, the decreased number and immunomodulatory function of MSCs could be associated with a delayed M1 clearance (i.e., apoptosis and/or polarization) and consequent delayed resolution of the inflammatory phase. Furthermore, M1-derived IL-38 may be associated with immunoregulation in the tissue regeneration site.

DOI： 10.3390/ijms25063252

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DO ORAL CARE AND REHABILITATION IMPROVE COGNITIVE FUNCTION? A SYSTEMATIC REVIEW OF CLINICAL STUDIES. Reviewed International journal

Yuka Inamochi, Yoichiro Ogino, Kae Harada, Kenji Fueki, Yasunori Ayukawa, Masahiro Nishimura, Kenji Maekawa, Youngnam Kang, Toshihiro Hirai, Takuo Kuboki

The journal of evidence-based dental practice 24 ( 1 ) 101948 - 101948 2024.3

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

OBJECTIVES: An increasing number of studies have identified an association between oral health status and cognitive function. However, the effect of oral interventions, including oral health care, dental treatment and oral motor exercises, on cognitive function remains unclear. This systematic review examined whether oral interventions contribute to the long-term improvement of cognitive status. METHODS: Four databases were searched (MEDLINE, Web of Science, Cochrane Library, and ICHUSHI Web) to identify randomized and nonrandomized controlled trial studies and prospective cohort studies from inception until 1 September 2023, published in English or Japanese. The Cochrane risk of bias tool for randomized controlled trials and the risk of bias assessment tool for nonrandomized studies were used to assess bias risk. RESULTS: A total of 20 articles were included in the qualitative analysis; 13 articles were published in English, and 7 were published in Japanese. The implemented interventions were oral care in 8 studies, dental treatment in 8 studies, and oral motor exercise in 4 studies. One study found a significant effect on attention following oral care intervention. Some dental treatments influenced cognitive function, although a clear positive effect was not determined. In 1 study, attention and working memory improved in the chewing exercise group. CONCLUSIONS: Several studies verified the improvement effects of oral interventions, such as oral care, dental treatment, and oral motor exercise, on cognitive function or impairment. However, there was still a lack of conclusive evidence that such an intervention clearly improved cognitive function. To clarify the effects of oral interventions on cognitive function, it is necessary to examine participants, interventions, and outcome measures in detail.

DOI： 10.1016/j.jebdp.2023.101948

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認知機能と口腔機能の相関に関する医師・歯科医師の意識調査医科歯科連携ECCOプロジェクト

笛木賢治, 眞鍋雄太, 佐々木啓一, 橋本衛, 木本克彦, 石川智久, 上田貴之, 内海久美子, 釘宮嘉浩, 白石成, 安部友佳, 稲用友佳, 馬場一美, 窪木拓男, 池田学

老年精神医学雑誌 35 ( 3 ) 283 - 290 2024.3

Language：Japanese Publisher：(株)ワールドプランニング

日本老年精神医学会と日本補綴歯科学会が共同で実施しているECCOプロジェクトでは,認知機能と口腔機能との関連について連携研究を進めている.本研究では,新たな研究課題を探索するために,認知症専門医と歯科医師を対象として,認知機能と口腔機能の相関に関する意識調査を行った.その結果,歯の喪失と口腔機能の低下が認知機能の低下と認知症の発症に関連する臨床経験,認知症の行動・心理症状(BPSD)が口腔の問題と関連する臨床経験,歯科治療により認知機能が改善した臨床経験を有する割合は医師と歯科医師で同程度であり,認知機能と口腔機能の関連は医師と歯科医師で共通認識であることが明らかになった.また,認知症の先制予防としてオーラルフレイルの改善に対する期待が高かった.以上の結果をもとに,BPSDと口腔機能との関連を解明する研究と口腔機能への介入が認知機能に及ぼす影響に関する研究をECCOプロジェクトの今後の課題に設定した.(著者抄録)

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Tooth morphology fusion technique is more accurate than conventional technique in transferring morphology of provisional to definitive screw-retained, implant-supported crown: A preliminary intervention study. Reviewed

Takuya Mino, Yoko Kurosaki, Kana Tokumoto, Koji Izumi, Hiroshi Mitsumune, Kenji Maekawa, Akihiro Ueda, Tomohito Nakano, Junichi Sejima, Aya Kimura-Ono, Takuo Kuboki

Journal of prosthodontic research 68 ( 1 ) 139 - 146 2024.1

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

PURPOSE: To compare the accuracy of the tooth morphology fusion (TMF) digital technique and customized impression transfer coping (conventional) technique when transferring the morphology of a provisional crown to a definitive screw-retained implant-supported crown. METHODS: Six cases of partial edentulism (one anterior and five posterior) treated with oral implant placement in our clinic for the loss of three or fewer teeth in the maxilla or mandible between April 2017 and September 2018 were included. After implant placement and re-entry surgery, provisional restorations were made and adjusted to obtain the ideal morphology. Two definitive restorations were constructed by transferring the complete morphology of the provisional restorations, including the subgingival contour, using the TMF digital and conventional techniques. Three sets of surface morphological data were obtained using a desktop scanner. The three-dimensional total discrepancy volume (TDV) between the provisional restoration (reference) and the two definitive restorations was digitally measured by overlapping the surface data of the stone cast using the Boolean operation. Each TDV ratio (%) was calculated by dividing the TDV by the volume of provisional restoration. The median TDV ratios for TMF and conventional techniques were compared using the Wilcoxon signed-rank test. RESULTS: The median TDV ratio between provisional and definitive restorations constructed using the TMF digital technique (8.05%) was significantly lower than that obtained using the conventional technique (13.56%, P < 0.05). CONCLUSIONS: In this preliminary intervention study, the TMF digital technique was more accurate than the conventional technique for the transfer of morphology from provisional to definitive prosthesis.

DOI： 10.2186/jpr.JPR_D_22_00244

PubMed

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