Updated on 2025/12/25

写真a

 
KUWAHARA Miho
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Assistant Professor
Position
Assistant Professor
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Degree

  • PhD ( 2021.3   Okayama University )

Education

  • Okayama University   大学院医歯薬学総合研究科   咬合・有床義歯補綴学分野

    2017.4 - 2021.3

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Papers

  • Critical Requirement of Senescence-Associated CCN3 Expression in CD44-Positive Stem Cells for Osteoarthritis Progression. International journal

    Janvier Habumugisha, Ryuichiro Okuda, Kazuki Hirose, Miho Kuwahara, Ziyi Wang, Mitsuaki Ono, Hiroshi Kamioka, Satoshi Kubota, Takako Hattori

    International journal of molecular sciences   26 ( 19 )   2025.10

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    Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and subchondral bone remodeling. Previous studies have shown that cellular communication network factor 3 (CCN3) expression increases with age in cartilage, and its overexpression promotes OA-like changes by inducing senescence-associated secretory phenotypes. This study aimed to investigate the effect of Ccn3 knockout (KO) on OA development using a murine OA model. Destabilization of the medial meniscus (DMM) surgery was performed in wild-type (WT) and Ccn3-KO mice. Histological scoring and staining were used to assess cartilage degeneration and proteoglycan loss. Gene and protein expressions of catabolic enzyme (Mmp9), hypertrophic chondrocyte marker (Col10a1), senescence marker, and cyclin-dependent kinase inhibitor 1A (Cdkn1a) were evaluated. Single-cell RNA sequencing (scRNA-seq) data from WT and Sox9-deficient cartilage were reanalyzed to identify Ccn3+ progenitor populations. Immunofluorescence staining assessed CD44 and Ki67 expression in articular cartilage. The effects of Ccn3 knockdown on IL-1β-induced Mmp13 and Adamts5 expression in chondrocytes were examined in vitro. Ccn3 KO mice exhibited reduced cartilage degradation and catabolic gene expression compared with WT mice post-DMM. scRNA-seq revealed enriched Ccn3-Cd44 double-positive cells in osteoblast progenitor, synovial mesenchymal stem cell, and mesenchymal stem cell clusters. Immunofluorescence showed increased CCN3+/CD44+ cells in femoral and tibial cartilage and meniscus. Ki67+ cells were significantly increased in DMM-treated Ccn3 KO cartilage, mostly CD44+. In vitro Ccn3 knockdown attenuated IL-1β-induced Mmp13 and Adamts5 expressions in chondrocytes. Ccn3 contributes to OA pathogenesis by promoting matrix degradation, inducing hypertrophic changes, and restricting progenitor cell proliferation, highlighting Ccn3 as a potential therapeutic target for OA.

    DOI： 10.3390/ijms26199630

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  • Initial Bonding Performance to CAD/CAM Restorative Materials: The Impact of Stepwise Concentration Variation in 8-Methacryloxyoctyl Trimethoxy Silane and 3-Methacryloxypropyl Trimethoxy Silane on Feldspathic Ceramic, Lithium Disilicate Glass-Ceramic, and Polymer-Infiltrated Ceramic. International journal

    Yukinori Maruo, Miho Kuwahara, Kumiko Yoshihara, Masao Irie, Noriyuki Nagaoka, Mai Yoshizane, Takuya Matsumoto, Kentaro Akiyama

    Materials (Basel, Switzerland)   18 ( 9 )   2025.4

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    This study investigated the effects of varying concentrations of two distinct silane agents, 8-methacryloxyoctyl trimethoxy silane (8-MOTS) and 3-methacryloxypropyl trimethoxy silane (γ-MPTS), on their initial bonding efficacy to feldspathic ceramic (FC), lithium disilicate glass-ceramic (LD) and polymer-infiltrated ceramic (PIC) specimens, in 10% increments for concentrations ranging from 10% to 40%. Shear bond strengths between the ceramic substrates and the luting material were assessed following 24 h incubation in distilled water. For FC, the median value of shear bond strength peaked at 20% of γ-MPTS (7.4 MPa), while 8-MOTS exhibited a concentration-dependent increase, reaching its highest value at 40% (13.1 MPa). For LD, γ-MPTS above 10% yielded similar strength median values (10.2 MPa), whereas 8-MOTS at 30% (15.8 MPa) and 40% (13.4 MPa) yielded higher strength values than at 10% (2.9 MPa) and 20% (4.1 MPa), with the highest median value exhibited at 30%. For PIC, both γ-MPTS and 8-MOTS demonstrated similarly low bond strength values which were not significantly different from the non-silane-treated specimens. When applied on silica-based FC and LD, silane revealed a concentration-dependent bonding effect, with 8-MOTS exhibiting superior bond strength to γ-MPTS. However, PIC, characterized by a high inorganic filler content, demonstrated limited bondability with both silanes.

    DOI： 10.3390/ma18091983

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  • 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

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  • Effects of intracerebral noradrenaline on cognitive decline associated with the loss of occlusal support. Reviewed

    Tomoka Ichikawa-Kato, Tetsuya Hara, Chie Yamada-Kubota, Miho Kuwahara, Asuka Murakami, Shogo Minagi

    Journal of prosthodontic research   69 ( 2 )   243 - 248   2024.8

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    PURPOSE: The lack of occlusal support reportedly reduces cognitive function; however, the underlying mechanisms remain unclear. The locus coeruleus, which is located adjacent to the trigeminal mesencephalic nucleus, secretes noradrenaline throughout the brain. In this study, we evaluated the effects of noradrenaline in the hippocampus and cerebral cortex on cognitive decline following tooth extraction in rats. METHODS: We performed passive avoidance experiments on male Wistar rats with extracted maxillary molars and determined the neuron density in the locus coeruleus and trigeminal mesencephalic nucleus using immunostaining and Nissl staining, respectively. We also assessed noradrenaline concentrations in the hippocampus and cerebral cortex using enzyme-linked immunosorbent assay. RESULTS: In the passive avoidance experiment, the latency in the bright compartment was significantly shorter (P < 0.05) in the extraction group than in the control group. The numbers of cells in the locus coeruleus and trigeminal nucleus were significantly lower (P < 0.05) in the extraction group compared to those in the control group. The noradrenaline levels in the hippocampus and cerebral cortex were also significantly lower (P < 0.05) in the extraction group than those in the control group. CONCLUSIONS: The lack of occlusal support associated with tooth extraction reduces the number of cells in the trigeminal mesencephalic nucleus and locus coeruleus, which may reduce the supply of noradrenaline to the cerebral cortex and hippocampus, leading to a decline in cognitive function.

    DOI： 10.2186/jpr.JPR_D_23_00231

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  • 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学術大会プログラム・抄録集   25回   28 - 28   2023.11

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    Language：Japanese   Publisher：日本口腔顎顔面技工学会  

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  • 軟骨組織の加齢とともに発現が上昇するCCN3は、その発現上昇と軟骨変性度が年齢、荷重の有無に関わらず相関する

    桑原 実穂, 廣瀬 一樹, 近藤 星, Fu Shanqi, 大野 充昭, 古松 毅之, 中田 英二, 滝川 正春, 久保田 聡, 服部 高子

    日本生化学会大会プログラム・講演要旨集   96回   [2P - 516]   2023.10

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    Language：Japanese   Publisher：(公社)日本生化学会  

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  • CCN3は軟骨細胞老化マーカーであり、年齢、荷重の有無に関わらず変形性関節症と相関する

    服部 高子, 滝川 正春, 久保田 聡, 桑原 実穂, 廣瀬 一樹

    Journal of Oral Biosciences Supplement   2023   [O3 - 03]   2023.9

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    Language：Japanese   Publisher：(一社)歯科基礎医学会  

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  • 軟骨組織におけるCCN3の老化マーカーとしての役割と、CCN3の異所性発現による加齢様退行性変化の促進

    桑原 実穂, 廣瀬 一樹, 近藤 星, 古松 毅之, 中田 英二, 原 哲也, 久保田 聡, 服部 高子

    日本結合組織学会学術大会プログラム・抄録集   55回   158 - 158   2023.6

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  • 軟骨組織におけるCCN3の老化マーカーとしての役割と、CCN3の異所性発現による加齢様退行性変化の促進

    桑原 実穂, 廣瀬 一樹, 近藤 星, 古松 毅之, 中田 英二, 原 哲也, 久保田 聡, 服部 高子

    日本結合組織学会学術大会プログラム・抄録集   55回   158 - 158   2023.6

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    Language：Japanese   Publisher：日本結合組織学会  

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  • 日常生活中の筋電図記録に混入し得るノイズ信号に関する研究

    皆木 省吾, 兒玉 直紀, 中原 龍一, 尾崎 敏文, 古寺 寛志, 北川 佳祐, 萬田 陽介, 田中 祐貴, 杉本 皓, 森 慧太朗, 山田 蘭子, 松岸 諒, 桑原 実穂

    日本顎口腔機能学会雑誌   29 ( 2 )   124 - 125   2023.3

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  • 日常生活中の筋電図記録に混入し得るノイズ信号に関する研究 Reviewed

    皆木 省吾, 兒玉 直紀, 中原 龍一, 尾崎 敏文, 古寺 寛志, 北川 佳祐, 萬田 陽介, 田中 祐貴, 杉本 皓, 森 慧太朗, 山田 蘭子, 松岸 諒, 桑原 実穂

    日本顎口腔機能学会雑誌   29 ( 2 )   124 - 125   2023.3

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  • Elevated Expression of CCN3 in Articular Cartilage Induces Osteoarthritis in Hip Joints Irrespective of Age and Weight Bearing. Reviewed International journal

    Kazuki Hirose, Miho Kuwahara, Eiji Nakata, Tomonori Tetsunaga, Kazuki Yamada, Kenta Saiga, Masaharu Takigawa, Toshifumi Ozaki, Satoshi Kubota, Takako Hattori

    International journal of molecular sciences   23 ( 23 )   2022.12

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    Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1β than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1β in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnfα, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.

    DOI： 10.3390/ijms232315311

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  • 軟骨組織の加齢変性におけるCCN3の機能

    桑原 実穂, 近藤 星, Fu Shanqi, 大野 充昭, 古松 毅之, 中田 英二, 滝川 正春, 服部 高子, 久保田 聡

    日本生化学会大会プログラム・講演要旨集   95回   1T14a - 08   2022.11

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  • 認知行動療法は覚醒時ブラキシズムを抑制できるか?

    三谷 裕子, 兒玉 直紀, 加藤 聖也, 北川 佳祐, 萬田 陽介, 古寺 寛志, 森 慧太朗, 長塚 弘亮, 川上 滋央, 足立 れいみ, 市川 知香, 松岸 諒, 山田 蘭子, 桑原 実穂, 杉本 皓, 皆木 省吾

    日本補綴歯科学会誌   14 ( 東北・北海道支部学術大会特別号 )   32 - 32   2022.10

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  • 持続的な甘味刺激が唾液分泌量に及ぼす影響

    山田 蘭子, 杉本 皓, 田中 祐貴, 北川 佳祐, 古寺 寛志, 足立 れいみ, 市川 知香, 松岸 諒, 森 慧太郎, 桑原 実穂, 萬田 陽介, 兒玉 直紀, 吉田 竜介, 皆木 省吾

    日本補綴歯科学会誌   14 ( 中国・四国支部学術大会特別号 )   22 - 22   2022.8

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  • Maternal Gut Microbiome Decelerates Fetal Endochondral Bone Formation by Inducing Inflammatory Reaction. Reviewed International journal

    Yoko Uchida-Fukuhara, Takako Hattori, Shanqi Fu, Sei Kondo, Miho Kuwahara, Daiki Fukuhara, Md Monirul Islam, Kota Kataoka, Daisuke Ekuni, Satoshi Kubota, Manabu Morita, Mika Iikegame, Hirohiko Okamura

    Microorganisms   10 ( 5 )   2022.5

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    DOI： 10.3390/microorganisms10051000

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  • 持続的な味刺激による唾液分泌量の経時変化に関する研究

    山田 蘭子, 杉本 皓, 田中 祐貴, 北川 佳祐, 古寺 寛志, 足立 れいみ, 才本 大稀, 小室 奈央, 谷地 開, 桑原 実穂, 萬田 陽介, 兒玉 直紀, 吉田 竜介, 皆木 省吾

    日本顎口腔機能学会雑誌   28 ( 2 )   76 - 77   2022.3

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  • Lack of occlusal support did not impact amyloid β deposition in APP knock-in mice. Reviewed

    Asuka Murakami, Tetsuya Hara, Chie Yamada-Kubota, Miho Kuwahara, Tomoka Ichikawa, Shogo Minagi

    Journal of prosthodontic research   66 ( 1 )   161 - 166   2022.1

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    PURPOSE: The lack of occlusal support is an epidemiological risk factor linked to Alzheimer's disease. This study sought to assess the relationship between amyloid β (Aβ) deposition and the lack of occlusal support in amyloid precursor protein (APP) knock-in mice. METHODS: Sixteen experimental animals were divided into two groups. The upper molars were extracted in the extraction group (group E), and a sham operation was performed in the control group (group C). The Morris water maze test was performed 4 months after the tooth extraction. Aβ immunohistochemical staining and Nissl staining of the hippocampus were performed. Hippocampal plasma corticosterone and Aβ protein levels were measured. RESULTS: In the maze task, the escape latency was significantly longer in group E than in group C. In the probe trials, the time elapsed in the target quadrant was significantly shorter in group E than in group C. The number of hippocampal neurons decreased in group E. There was no significant difference in the plasma corticosterone levels between the two groups, indicating that there was no effect of chronic stress on the behavioral results. Hippocampal Aβ40 and Aβ42 protein levels and Aβ deposition areas by immunohistochemical staining were not significantly different between the two groups. CONCLUSIONS: Aβ deposition was not increased in the hippocampus of molarless APP knock-in mice. As such, it appears that cognitive impairment due to a lack of occlusal support was not related to Aβ deposition.

    DOI： 10.2186/jpr.JPR_D_20_00205

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  • Newly designed flat surface artificial tongue system for speech improvement in glossectomy patients: A preliminary study. Reviewed

    Hiroaki Nagatsuka, Shigehisa Kawakami, Miho Kuwahara, Chie Kubota, Naoki Kodama, Shogo Minagi

    Journal of prosthodontic research   66 ( 1 )   87 - 92   2022.1

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    PURPOSE: To design an efficient tongue prosthesis with reproducibility and to objectively evaluate improvement in speech function. METHODS: A silicon anatomical artificial tongue (AT) and a flat surface artificial tongue system (FTS) were used in our study. Twenty healthy participants (10 males and 10 females, 26.3 ± 1.8 years) were fitted with a tongue movement suppression appliance (TSA) that fit the dental arch to simulate the glossectomy condition. TSA, TSA + FTS, and TSA + AT simulated the state of glossectomy patients without artificial tongue, with normal artificial tongue, and newly designed artificial tongue, respectively. Three speech intelligibility tests were performed for each of the following conditions: pronouncing 100 Japanese monosyllables, 40 Japanese words, and reading a short story. One-way ANOVA, Wilcoxon signed-rank test, and Tukey-Kramer post-hoc test were used for statistical analyses. RESULTS: Significant differences were observed for 100 Japanese monosylla bles and 40 Japanese words between the TSA + FTS, TSA, and TSA + AT conditions (p ‹ 0.05). Regarding the speech intelligibility test for reading a short story, the TSA + FTS condition resulted in a significantly higher speech intelligibility than the TSA and TSA + AT conditions (p ‹ 0.05). CONCLUSIONS: A flat surface artificial tongue system contributed to the improvement in speech function. This structure can be easily used in cases where conventional artificial tongue are applicable, regardless of variation in the oral condition; thus, making it a widely applicable treatment option for glossectomy patients.

    DOI： 10.2186/jpr.JPR_D_20_00230

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  • CCN3 (NOV) Drives Degradative Changes in Aging Articular Cartilage. Reviewed International journal

    Miho Kuwahara, Koichi Kadoya, Sei Kondo, Shanqi Fu, Yoshiko Miyake, Ayako Ogo, Mitsuaki Ono, Takayuki Furumatsu, Eiji Nakata, Takako Sasaki, Shogo Minagi, Masaharu Takigawa, Satoshi Kubota, Takako Hattori

    International journal of molecular sciences   21 ( 20 )   2020.10

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    Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-β gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21.

    DOI： 10.3390/ijms21207556

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  • Circadian production of melatonin in cartilage modifies rhythmic gene expression. Reviewed International journal

    Shanqi Fu, Miho Kuwahara, Yoko Uchida, Sei Koudo, Daichi Hayashi, Yuji Shimomura, Asami Takagaki, Takashi Nishida, Yusuke Maruyama, Mika Ikegame, Atsuhiko Hattori, Satoshi Kubota, Takako Hattori

    The Journal of endocrinology   241 ( 2 )   161 - 173   2019.3

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    Endochondral ossification, including bone growth and other metabolic events, is regulated by circadian rhythms. Herein, we provide evidence that melatonin has a direct effect on the circadian rhythm of chondrocytes. We detected mRNA expression of the genes which encode the melatonin-synthesizing enzymes AANAT (arylalkylamine N-acetyltransferase) and HIOMT (hydroxyindole O-methyltransferase), as well as the melatonin receptors MT1 and MT2 in mouse primary chondrocytes and cartilage. Production of melatonin was confirmed by mass spectrometric analysis of primary rat and chick chondrocytes. Addition of melatonin to primary mouse chondrocytes caused enhanced cell growth and increased expression of Col2a1, Aggrecan, and Sox9, but inhibited Col10a1 expression in primary BALB/c mouse chondrocytes. Addition of luzindole, an MT1 and MT2 antagonist, abolished these effects. These data indicate that chondrocytes produce melatonin, which regulates cartilage growth and maturation via the MT1 and MT2 receptors. Kinetic analysis showed that melatonin caused rapid upregulation of Aanat, Mt1, Mt2, and Pthrp expression, followed by Sox9 and Ihh. Furthermore, expression of the clock gene Bmal1 was induced, while that of Per1 was downregulated. Chronobiological analysis of synchronized C3H mouse chondrocytes revealed that melatonin induced the cyclic expression of Aanat and modified the cyclic rhythm of Bmal1, Mt1, and Mt2. In contrast, Mt1 and Mt2 showed different rhythms from Bmal1 and Aanat, indicating the existence of different regulatory genes. Our results indicate that exogenous and endogenous melatonin work in synergy in chondrocytes to adjust rhythmic expression to the central suprachiasmatic nucleus clock.

    DOI： 10.1530/JOE-19-0022

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  • 軟骨におけるメラトニンとその受容体の日周的合成は軟骨の律動的遺伝子発現に影響を及ぼす(Circadian production of melatonin and its receptors in cartilage influences chondrocyte rhythmic gene expression)

    Fu Shanqi, 桑原 実穂, 内田 瑶子, 林 大智, 下村 侑司, 高垣 安紗美, 西田 崇, 丸山 雄介, 池亀 美華, 服部 淳彦, 服部 高子, 久保田 聡

    日本生化学会大会プログラム・講演要旨集   91回   [1T14m - 250)]   2018.9

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  • BMP2含有光重合型PDVAで補強したコラーゲンスポンジによる吸収性骨補填材

    山田 知枝, 原 哲也, 田仲 持郎, 清瀧 優也, 村上 明日香, 桑原 実穂, 伊志嶺 知沙[黒田], 坂本 隼一, 荒木 大介[飯田], 玉田 祥与, 宮崎 貴子, 皆木 省吾

    日本補綴歯科学会誌   10 ( 特別号 )   272 - 272   2018.6

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  • CCN3の軟骨特異的過剰発現は内軟骨性骨形成の遅延を誘発する

    角谷 宏一, 服部 高子, 桑原 実穂, 大野 充昭, 星島 光博, 窪木 拓男, 滝川 正春

    Journal of Oral Biosciences Supplement   2013   138 - 138   2013.9

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    Language：Japanese   Publisher：(一社)歯科基礎医学会  

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  • CCNファミリー研究のメルティングポット 軟骨特異切CCN3過剰発現による内軟骨性骨形成の修飾

    服部 高子, 大野 充昭, 星島 光博, 角谷 宏一, 桑原 実穂, 三宅 佳子, 窪木 拓男, 滝川 正春

    Journal of Oral Biosciences Supplement   2013   94 - 94   2013.9

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  • CCN3は関節軟骨の加齢性変性を促進する

    桑原 実穂, 近藤 星, Fu Shanqi, 大野 充昭, 古松 毅之, 中田 英二, 滝川 正春, 久保田 聡, 服部 高子

    日本骨代謝学会学術集会プログラム抄録集   39回   138 - 138   2021.10

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  • CCN3 as a chondrocytic aging-accelerating factor

    桑原実穂, 武内聡子, 近藤星, FU Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部高子

    日本軟骨代謝学会プログラム・抄録集   33rd   2020

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  • 抜歯したラットの咀嚼筋におけるカテプシンBとBDNFの遺伝子発現の変化

    原 哲也, 加藤 知香[市川], 角谷 実穂[桑原]

    日本補綴歯科学会誌   16 ( 特別号 )   300 - 300   2024.7

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  • 上下無歯顎者におけるニュートラルゾーンの記録法と形態の違いに関するデジタル評価

    松岸 諒, 愛甲 文音, 兒玉 直紀, 庄賀 春生, 丸尾 幸憲, 萬田 陽介, 田中 祐貴, 杉本 皓, 角谷 実穂[桑原], 森 慧太朗, 北川 佳祐, 加藤 知香[市川], 原 哲也

    日本補綴歯科学会誌   16 ( 特別号 )   183 - 183   2024.7

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  • 軟骨組織においてCCN3は加齢に伴って発現上昇するが,その発現上昇は,年齢,荷重の有無に関わらず軟骨変性度と相関する

    服部高子, 桑原実穂, 廣瀬一樹, 近藤星, FU Shanqi, 滝川正春, 久保田聡

    日本骨代謝学会学術集会プログラム抄録集(CD-ROM)   42nd   170 - 170   2024

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    J-GLOBAL

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  • 咬合支持の喪失による三叉神経中脳路核と青斑核の変化と認知機能低下のメカニズム

    加藤 知香[市川], 原 哲也, 村上 明日香, 窪田 知枝[山田], 角谷 実穂[桑原], 皆木 省吾

    日本補綴歯科学会誌   15 ( 特別号 )   147 - 147   2023.5

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  • BMP2含有光重合型PDVA骨補填材における触媒量と骨置換効果

    窪田 知枝[山田], 原 哲也, 加藤 知香[市川], 角谷 実穂[桑原], 村上 明日香, 田仲 持郎

    日本補綴歯科学会誌   15 ( 特別号 )   259 - 259   2023.5

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  • CCN3, a senescence marker of cartilage, correlate with osteoarthritis irrespective of age and weight bearing

    桑原実穂, 廣瀬一樹, 廣瀬一樹, 奥田龍一郎, HABUMUGISHA Janvier, 近藤星, FU Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部高子

    日本分子生物学会年会プログラム・要旨集(Web)   46th   2023

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  • 変形性股関節症とCCN3発現の相関

    廣瀬 一樹, 中田 英二, 鉄永 智紀, 山田 和希, 佐藤 嘉洋, 小浦 卓, 服部 高子, 桑原 実穂, 滝川 正春, 久保田 聡, 尾崎 敏文

    日本整形外科学会雑誌   96 ( 8 )   S1583 - S1583   2022.9

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  • 持続的な甘味刺激が唾液分泌量に及ぼす影響

    山田 蘭子, 杉本 皓, 田中 祐貴, 北川 佳祐, 古寺 寛志, 足立 れいみ, 市川 知香, 松岸 諒, 森 慧太郎, 桑原 実穂, 萬田 陽介, 兒玉 直紀, 吉田 竜介, 皆木 省吾

    日本補綴歯科学会誌   14 ( 中国・四国支部学術大会特別号 )   22 - 22   2022.8

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  • 変形性肩関節症とCCN3発現上昇との相関について

    廣瀬 一樹, 中田 英二, 服部 高子, 鉄永 智紀, 山田 和希, 佐藤 嘉洋, 桑原 実穂, 滝川 正春, 久保田 聡, 尾崎 敏文

    移植   56 ( 4 )   455 - 455   2022.2

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  • Induction of non-coding RNA and promotion of chondrocyte differentiation by metformin

    近藤星, 近藤星, 服部高子, 桑原実穂, FU Shanqi, 西田崇, 薬師寺翔太, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    日本軟骨代謝学会プログラム・抄録集   34th   2022

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  • 変形性股関節症とCCN3発現の相関

    廣瀬一樹, 廣瀬一樹, 服部高子, 桑原実穂, 滝川正春, 中田英二, 鉄永智紀, 山田和希, 佐藤嘉洋, 小浦卓, 尾崎敏文, 久保田聡

    日本骨代謝学会学術集会プログラム抄録集(CD-ROM)   40th ( 8 )   124 - 124   2022

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    J-GLOBAL

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  • Metformin regulates expression of long non-coding RNA, UCA1 and CCN2 in chondrocytes

    近藤星, 近藤星, 服部高子, 桑原実穂, FU Shanqi, 西田崇, 薬師寺翔太, 吉岡洋祐, 森谷徳文, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    日本分子生物学会年会プログラム・要旨集(Web)   45th   2022

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  • メトホルミンによるUCA1を介した軟骨保護作用の解析

    近藤 星, 服部 高子, 桑原 実穂, Fu Shanqi, 西田 崇, 薬師寺 翔太, 吉岡 洋祐, 森谷 徳文, 飯田 征二, 滝川 正春, 久保田 聡

    岡山歯学会雑誌   40 ( 2 )   38 - 39   2021.12

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  • 変形性肩関節症モデルとしてのCCN3過剰発現マウス

    廣瀬 一樹, 服部 高子, 中田 英二, 鉄永 智紀, 山田 和希, 佐藤 嘉洋, 桑原 実穂, 尾崎 敏文, 滝川 正春, 久保田 聡

    日本骨代謝学会学術集会プログラム抄録集   39回   151 - 151   2021.10

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  • 変形性肩関節症とCCN3発現上昇との相関について

    廣瀬 一樹, 中田 英二, 服部 高子, 鉄永 智紀, 山田 和希, 佐藤 嘉洋, 桑原 実穂, 滝川 正春, 久保田 聡, 尾崎 敏文

    日本整形外科学会雑誌   95 ( 8 )   S1506 - S1506   2021.8

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  • 変形性肩関節症とCCN3発現上昇との相関について

    廣瀬 一樹, 中田 英二, 服部 高子, 鉄永 智紀, 山田 和希, 佐藤 嘉洋, 桑原 実穂, 滝川 正春, 久保田 聡, 尾崎 敏文

    日本整形外科学会雑誌   95 ( 8 )   S1506 - S1506   2021.8

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  • 変形性肩関節症とCCN3発現上昇との相関について

    廣瀬一樹, 中田英二, 服部高子, 鉄永智紀, 山田和希, 佐藤嘉洋, 桑原実穂, 滝川正春, 久保田聡, 尾崎敏文

    移植(Web)   56 ( 4 )   2021

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  • non-coding RNAを介したメトホルミンの抗線維化作用の解析

    近藤星, 近藤星, 服部高子, 桑原実穂, FU Shanqi, 西田崇, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 滝川正春, 久保田聡

    日本口腔科学会学術集会プログラム・抄録集   75th   2021

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  • メトホルミンのUCA1誘導および軟骨細胞分化促進作用

    近藤星, 近藤星, 服部高子, 桑原実穂, FU Shanqi, 西田崇, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    日本生化学会大会(Web)   94th   2021

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  • Metformin promotes chondrocyte differentiation, which is accompanied by UCA1 induction.

    近藤星, 近藤星, 服部高子, 桑原実穂, FU Shanqi, 西田崇, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    日本分子生物学会年会プログラム・要旨集(Web)   44th   2021

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  • アルツハイマーモデルマウスを用いた咬合支持の欠如によるアミロイドβ沈着の変化

    村上 明日香, 原 哲也, 山田 知枝, 桑原 実穂, 荒木 大介, 皆木 省吾

    日本補綴歯科学会誌   12 ( 特別号 )   202 - 202   2020.6

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  • Changes in amyloid β deposition due to lack of occlusal support in Alzheimer model mice

    村上明日香, 原哲也, 山田知枝, 桑原実穂, 荒木大介, 皆木省吾

    日本補綴歯科学会誌(Web)   12   2020

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  • Effect of melatonin on rhythmic gene expression in human articular chondrocytes

    FU Shanqi, 桑原実穂, 内田瑶子, 林大智, 下村侑司, 高垣安紗美, 西田崇, 中田英二, 古松毅之, 近藤星, 丸山雄介, 服部淳彦, 久保田聡, 服部高子

    日本生化学会大会(Web)   93rd   2020

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  • non-coding RNAを介したメトホルミンの抗線維化作用の解析

    近藤星, 近藤星, 服部高子, 桑原実穂, FU Shanqi, 西田崇, 吉岡洋祐, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    日本分子生物学会年会プログラム・要旨集(Web)   43rd   2020

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  • メトホルミンの軟骨細胞分化に対する作用の解析

    近藤星, 近藤星, 服部高子, 桑原実穂, FU Shanqi, 森谷徳文, 飯田征二, 滝川正春, 久保田聡

    岡山歯学会雑誌   39 ( 2 )   2020

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  • The impact of gut microbiome on embryonic endochondral ossification

    内田瑶子, 服部高子, 福原大樹, FU Shanqi, 近藤星, 桑原実穂, ISLAM Monirul, 片岡広太, 江國大輔, 久保田聡, 森田学

    日本軟骨代謝学会プログラム・抄録集   33rd   2020

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  • Effect of melatonin on rhythmic gene expression in human articular cartilage

    フシャンキ, 桑原実穂, 内田瑶子, 近藤星, 西田崇, 池亀美華, 久保田聡, 服部高子

    日本骨代謝学会学術集会プログラム抄録集(CD-ROM)   38th   2020

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  • 軟骨組織におけるCCN3の老化促進作用

    桑原実穂, 桑原実穂, 近藤星, FU Shanqi, 大野充昭, 古松毅之, 中田英二, 皆木省吾, 滝川正春, 久保田聡, 服部高子

    日本分子生物学会年会プログラム・要旨集(Web)   43rd   2020

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  • CCNは軟骨細胞の加齢に伴い発現上昇し,過剰発現は軟骨加齢を促進する

    桑原実穂, 武内聡子, 近藤星, FU Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部高子

    岡山歯学会雑誌   38 ( 2 )   2019

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  • 軟骨細胞は加齢にともなってCCN3を高発現し,その過剰発現は軟骨加齢を促進する

    桑原実穂, 武内聡子, 近藤星, FU Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部高子

    日本分子生物学会年会プログラム・要旨集(Web)   42nd   2019

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  • 長鎖(約6kb)lssODNおよびCRISPR/Cas9を用いたヒト科霊長類特異的lncRNAのマウス受精卵へのエレクトロポレーションによるノックインの試み

    近藤星, 桑原実穂, FU Shanqi, 武内聡子, 池田健司, 石川崇典, 大野充昭, 西田崇, 久保田聡, 服部高子

    日本生化学会大会(Web)   92nd   2019

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  • 軟骨細胞は松果体由来のメラトニン刺激で概日リズムを持ってメラトニンを産生し,増殖を促進し,肥大化を抑制する

    FU Shanqi, 桑原実穂, 内田揺子, 近藤星, 西田崇, 池亀美華, 久保田聡, 服部高子

    日本骨代謝学会学術集会プログラム抄録集   37th   2019

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  • BMP2含有光重合型PDVAで補強したコラーゲンスポンジによる吸収性骨補填材

    山田知枝, 原哲也, 田仲持郎, 清瀧優也, 村上明日香, 桑原実穂, 伊志嶺(黒田)知沙, 坂本隼一, 荒木大介, 玉田(飯田)祥与, 宮崎貴子, 皆木省吾

    日本補綴歯科学会誌(Web)   10   2018

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  • 長鎖(約6kb)ssODNおよびCRISPR/Cas9を用いたヒト科霊長類特異的lncRNAのマウス受精卵へのエレクトロポレーションによる高効率ノックインの試み

    近藤星, 桑原実穂, FU Shanqi, 池田健司, 石川崇典, 大野充昭, 西田崇, 久保田聡, 服部高子

    日本分子生物学会年会プログラム・要旨集(Web)   41st   2018

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  • 軟骨組織におけるメラトニン合成とその受容体発現は概日リズムを持ち,軟骨細胞の代謝に影響を及ぼす

    服部高子, FU Shanqi, 桑原実穂, 内田瑶子, 近藤星, 林大智, 下村侑司, 高垣安紗美, 西田崇, 丸山雄介, 池亀美華, 服部淳彦, 久保田聡

    日本生化学会大会(Web)   90th   2017

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  • 軟骨特異的CCN3過剰発現は内軟骨性骨化の遅延と関節変性を誘発する

    服部高子, 角谷宏一, 桑原実穂, 大野充昭, 星島光博, 星島光博, 窪木拓男, 久保田聡, 久保田聡, 滝川正春, 滝川正春

    日本骨代謝学会学術集会プログラム抄録集   33rd   2015

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  • 軟骨特異的CCN3過剰発現は内軟骨性骨形成の遅延による骨梁形成の低下を誘発する

    服部高子, 大野充昭, 星島光博, 角谷宏一, 桑原実穂, 大家遥, 三宅佳子, 窪木拓男, 滝川正春

    日本軟骨代謝学会プログラム・抄録集   26th   2013

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  • 軟骨特異的CCN3過剰発現は内軟骨性骨形成の不全より骨異形性を誘発する

    服部高子, 大野充昭, 星島光博, 角谷宏一, 桑原実穂, 三宅佳子, 窪木拓男, 滝川正春

    日本分子生物学会年会プログラム・要旨集(Web)   36th   2013

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  • CCN3の軟骨特異的過剰発現は内軟骨性骨形成の遅延を誘発する

    角谷宏一, 服部高子, 桑原実穂, 大野充昭, 星島光博, 窪木拓男, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2013   2013

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  • 軟骨特異的CCN3過剰発現による内軟骨性骨形成の修飾

    服部高子, 大野充昭, 星島光博, 角谷宏一, 桑原実穂, 三宅佳子, 窪木拓男, 滝川正春

    Journal of Oral Biosciences Supplement (Web)   2013   2013

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  • CCN3/NOVの軟骨特異的過剰発現は軟骨分化の最終段階に影響を及ぼす事により骨形成不全をきたす

    服部高子, 大野充昭, 星島光博, 角谷宏一, 桑原実穂, 三宅佳子, 窪木拓男, 滝川正春

    日本生化学会大会(Web)   85th   2012

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Presentations

  • CCN3は関節軟骨の加齢性変性を促進する

    桑原 実穂, 近藤 星, Fu Shanqi, 大野 充昭, 古松 毅之, 中田 英二, 滝川 正春, 久保田 聡, 服部 高子

    日本骨代謝学会学術集会プログラム抄録集  2021.10  (一社)日本骨代謝学会

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  • CCN3 as a chondrocytic aging-accelerating factor

    桑原実穂, 武内聡子, 近藤星, FU Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 久保田聡, 服部高子

    日本軟骨代謝学会プログラム・抄録集  2020 

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    Event date： 2020

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  • 軟骨組織の加齢変性におけるCCN3の機能

    桑原実穂, 近藤星, Fu Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 服部高子, 久保田聡

    第95回日本生化学会大会  2022.10.11 

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    Event date： 2022.10.9 - 2022.10.11

    Presentation type：Poster presentation  

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  • 軟骨組織の加齢変性におけるCCN3の機能

    桑原実穂, 近藤星, Fu Shanqi, 大野充昭, 古松毅之, 中田英二, 滝川正春, 服部高子, 久保田聡

    第95回日本生化学会大会  2022.10.9 

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    Event date： 2022.10.9 - 2022.10.11

    Presentation type：Oral presentation (general)  

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  • 持続的な味刺激による唾液分泌量の経時的変化に関する研究

    山田蘭子, 杉本皓, 田中祐貴, 北川佳祐, 古寺寛志, 足立れいみ, 桑原実穂, 萬田陽介, 兒玉直紀, 吉田竜介, 皆木省吾

    日本顎口腔機能学会第66回学術大会  2021.12.4 

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    Event date： 2021.12.4 - 2021.12.5

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  • 持続的な甘味刺激が唾液分泌量に及ぼす影響

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Research Projects

  • Mechanism of chondrocyte senescence mediated by CCN3

    Grant number：20K18601  2020.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Kuwahara Miho

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    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

    In this study, we showed a positive correlation between age and the expression level of CCN3 in primary human articular chondrocytes. The CCN3 expression levels was upregulated by inducing cellular senescence also. In addition, degenerative changes were observed in the articular cartilage of cartilage-specific CCN3 overexpressing mice, and increased production of cell senescence-associated secretory trait (SASP) factors was confirmed. Furthermore, analysis of promoter gene assay suggests that CCN3 increases p21 activity via induction of p53.

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  • 高齢者根面う蝕の予測数理モデルと新規接着システム創製の統合研究

    Grant number：25K13286  2025.04 - 2029.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    丸尾 幸憲, 田中 祐貴, 桑原 実穂, 長岡 紀幸, 猪越 正直

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

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  • 舌再建術後の構音障害に対するデジタル技術を用いた評価法と最適治療法の確立への挑戦

    Grant number：25K13314  2025.04 - 2028.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    兒玉 直紀, 萬田 陽介, 桑原 実穂, 丸尾 幸憲, 戸原 玄

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

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  • 下顎頭軟骨変性を制御する分子メカニズムの解明

    Grant number：24K13004  2024.04 - 2027.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    桑原 実穂, 原 哲也, 丸尾 幸憲, 服部 高子, 角谷 宏一

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    Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）

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  • Effects of myokines on cognitive decline caused by loss of occlusal support and decline in masticatory function

    Grant number：24K13025  2024.04 - 2027.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    原 哲也, 桑原 実穂

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    Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）

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  • Elucidation of a Novel Mechanism for Controlling Aging of Temporomandibular Joint Cartilage

    Grant number：22K17137  2022.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Kuwahara Miho

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

    Immunostaining of CCN3 in the femoral head samples collected from healthy adults and patients with osteoarthritis (OA) revealed an accumulation of positive cells in the superficial layer of chondrocytes and highly stained areas in the matrix of the cartilage surface in the OA group. Moreover, gene analysis of isolated chondrocytes showed a significant increase in CCN3 mRNA expression in the OA group compared to the healthy group, along with induction of expression of genes such as p16, ADAMTS4, and Aggrecan mRNA. Furthermore, a positive correlation was observed between the histological degeneration degree obtained by the Mankin score of the same samples and the expression level of CCN3 mRNA.

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  • Mechanism of hippocampal pyramidal cell degeneration by reduced periodontal ligament stimulation: Neural pathway via the locus coeruleus

    Grant number：21K10000  2021.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hara Tetsuya

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    Grant amount：\4030000 （ Direct expense: \3100000 、 Indirect expense：\930000 ）

    We investigated the mechanism by which cognitive function declines with loss of occlusal support. The number of cells in the mesencephalic trigeminal nucleus and the locus coeruleus cells, where noradrenaline-containing neurons that affect cognitive function are gathered, decreased, and the amount of adrenaline in the brain also decreased. These results suggested that the cognitive impairment associated with loss of occlusal support is affected by a decrease in the noradrenaline amount in the brain.

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Class subject in charge

  • The design of removable partial dentures （2025academic year） 1st semester  - 水5,水6,水7

  • Laboratory protocol for removable patial dentures （2025academic year） Second semester  - 水4～8

  • Exercise for dental health care （2023academic year） 1st and 2nd semester  - 火1～3