Faculty Profiles - NAKADA Eiji

Papers - NAKADA Eiji

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杉原進介, 近藤宏也, 中田英二, 尾崎敏文

日本整形外科学会雑誌 97 ( 3 ) S618 - S618 2023.3

A novel chondrocyte sheet fabrication using human-induced pluripotent stem cell-derived expandable limb-bud mesenchymal cells. International journal

Tomoka Takao, Masato Sato, Yuki Fujisawa, Eriko Toyoda, Daisuke Yamada, Yukio Hitsumoto, Eiji Nakata, Toshifumi Ozaki, Takeshi Takarada

Stem cell research & therapy 14 ( 1 ) 34 - 34 2023.2

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

BACKGROUND: Cell sheet fabrication for articular cartilage regenerative medicine necessitates a large number of chondrocytes of consistent quality as a cell source. Previously, we have developed human-induced pluripotent stem cell (iPSC)-derived expandable PRRX1+ limb-bud mesenchymal cells (ExpLBM) with stable expansion and high chondrogenic capacity, while in this study; our ExpLBM technology was combined with cell sheet engineering to assess its potential as a stable cell source for articular cartilage regeneration. METHODS: ExpLBM cells derived from human-induced pluripotent stem cells (hiPSCs), including 414C2 and Ff-KVs09 (HLA homozygous), were seeded onto a culture plate and two-dimensional chondrogenic induction (2-DCI) was initiated. After 2-DCI, ExpLBM-derived chondrocytes were stripped and transferred to temperature-responsive culture inserts and the chondrocyte sheets were histologically examined or transplanted into osteochondral knee defects of immunodeficient rats. RESULTS: Immunohistochemistry revealed that ExpLBM-derived cell sheets were positive for Safranin O, COL2, and ACAN but that they were negative for COL1 and RUNX2. Furthermore, the engrafted tissues in osteochondral knee defects in immunodeficient rats were stained with SafO, human VIMENTIN, ACAN, and COL2. CONCLUSIONS: The present study is the first to report the chondrocyte sheet fabrication with hiPSC-derived cell source. hiPSC-derived ExpLBM would be a promising cell source for cell sheet technology in articular cartilage regenerative medicine.

DOI： 10.1186/s13287-023-03252-4

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CDKAL1 Drives the Maintenance of Cancer Stem-Like Cells by Assembling the eIF4F Translation Initiation Complex. International journal

Rongsheng Huang, Takahiro Yamamoto, Eiji Nakata, Toshifumi Ozaki, Kazuhiko Kurozumi, Fanyan Wei, Kazuhito Tomizawa, Atsushi Fujimura

Advanced science (Weinheim, Baden-Wurttemberg, Germany) e2206542 2023.2

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

Cancer stem-like cells (CSCs) have a unique translation mode, but little is understood about the process of elongation, especially the contribution of tRNA modifications to the maintenance of CSCs properties. Here, it is reported that, contrary to the initial aim, a tRNA-modifying methylthiotransferase CDKAL1 promotes CSC-factor SALL2 synthesis by assembling the eIF4F translation initiation complex. CDKAL1 expression is upregulated in patients with worse prognoses and is essential for maintaining CSCs in rhabdomyosarcoma (RMS) and common cancers. Translatome analysis reveals that a group of mRNAs whose translation is CDKAL1-dependent contains cytosine-rich sequences in the 5' untranslated region (5'UTR). Mechanistically, CDKAL1 promotes the translation of such mRNAs by organizing the eIF4F translation initiation complex. This complex formation does not require the enzyme activity of CDKAL1 but requires only the NH2 -terminus domain of CDKAL1. Furthermore, sites in CDKAL1 essential for forming the eIF4F complex are identified and discovered candidate inhibitors of CDKAL1-dependent translation.

DOI： 10.1002/advs.202206542

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遺伝性骨・軟部腫瘍外来におけるNF-1の診療

中田英二, 二川摩周, 藤原智洋, 国定俊之, 山本英喜, 平沢晃, 尾崎敏文

日本レックリングハウゼン病学会学術大会プログラム・抄録集 14回 33 - 33 2023.2

神経線維腫症1型における院内レジストリの構築と定期的なサーベイランスの実施

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 山本英喜, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本レックリングハウゼン病学会学術大会プログラム・抄録集 14回 34 - 34 2023.2

悪性末梢神経鞘腫瘍におけるPRRX1の悪性化因子としての役割

たき平将太, 中田英二, 山田大祐, 片山晴喜, 畑利彰, 藤原智洋, 高尾知佳, 国定俊之, 宝田剛志, 尾崎敏文

日本レックリングハウゼン病学会学術大会プログラム・抄録集 14回 16 - 16 2023.2

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

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

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

軟部肉腫に対する薬物療法がん遺伝子パネルに基づく肉腫診療

中田英二, 藤原智洋, 国定俊之, 平沢晃, 遠西大輔, 尾崎敏文

中部日本整形外科災害外科学会雑誌 65 ( 秋季学会 ) 77 - 77 2022.10

がん遺伝子パネルに基づく肉腫診療

中田英二, 藤原智洋, 平沢晃, 二川摩周, 遠西大輔, 山本英喜, 冨田秀太, 久保寿夫, 田端雅弘, 国定俊之, 豊岡伸一, 尾崎敏文

日本癌治療学会学術集会抄録集 60回 O49 - 4 2022.10

がん遺伝子パネルに基づく肉腫診療

中田英二, 藤原智洋, 平沢晃, 二川摩周, 遠西大輔, 山本英喜, 冨田秀太, 久保寿夫, 田端雅弘, 国定俊之, 豊岡伸一, 尾崎敏文

日本癌治療学会学術集会抄録集 60回 O49 - 4 2022.10

下肢長幹骨発生の原発性悪性骨腫瘍に対する広範切除術後の機能回復は再建法によりどのように異なるか?

藤原智洋, 中田英二, 堅山佳美, 濱田全紀, 国定俊之, 尾崎敏文, 千田益生

The Japanese Journal of Rehabilitation Medicine 59 ( 秋季特別号 ) S364 - S364 2022.10

60歳以上の術前がん患者のがんロコモとサルコペニア,フレイルの有病率

堅山佳美, 中田英二, 藤原智洋, 國定俊之, 濱田全紀, 千田益生, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 59 ( 秋季特別号 ) S363 - S363 2022.10

骨盤悪性腫瘍に対するHip transposition法の術後機能・歩行能力

国定俊之, 中田英二, 藤原智洋, 尾崎敏文, 堅山佳美, 濱田全紀, 千田益生

The Japanese Journal of Rehabilitation Medicine 59 ( 秋季特別号 ) S364 - S364 2022.10

小児固形腫瘍における基礎・トランスレーショナル研究の現状と展望骨軟部肉腫における基礎・トランスレーショナル研究の現状と展望

藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本小児血液・がん学会雑誌 59 ( 4 ) 169 - 169 2022.10

がんロコモを予防するための骨転移患者のマネージメントデータに基づく骨転移診療

中田英二, 濱田全紀, 国定俊之, 藤原智洋, 堅山佳美, 千田益生, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 59 ( 秋季特別号 ) S322 - S322 2022.10

片側下腿に発生した多発性グロムス腫瘍の一例

徳田貴大, 藤原智洋, 国定俊之, 中田英二, 尾崎敏文

中国・四国整形外科学会雑誌 34 ( 3 ) 395 - 395 2022.10

下肢悪性軟部腫瘍に対する広範切除術後の機能改善について

廣瀬晃平, 岩井賢司, 増田翔太, 太田晴之, 堅山佳美, 濱田全紀, 藤原智洋, 中田英二, 千田益生

The Japanese Journal of Rehabilitation Medicine 59 ( 秋季特別号 ) S509 - S509 2022.10

Clinicopathological and histological analysis of secondary malignant giant cell tumors of bone without radiotherapy. International journal

Eiji Nakata, Hotaka Kawai, Tomohiro Fujiwara, Toshiyuki Kunisada, Hirofumi Inoue, Mashu Futagawa, Haruyoshi Katayama, Takuto Itano, Toshifumi Ozaki

Oncology letters 24 ( 3 ) 319 - 319 2022.9

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

Giant cell tumor of bone (GCTB) is an intermediate bone tumor that rarely undergoes malignant transformation. Secondary malignant GCTB (SMGCTB) is defined as a lesion in which high-grade sarcoma occurs at the site of previously treated GCTB. The present study retrospectively reviewed the medical records of patients with GCTB treated at Okayama University Hospital between April 1986 and April 2020. The clinicopathological and histological features of patients with SMGCTB without prior radiotherapy were investigated. A total of three patients (4%) with SMGCTB were detected, and the tumor sites were the distal ulna, distal femur and sacrum. Two of the patients had been treated with curettage and bone graft, and one had been treated with denosumab. In all cases, the lesions were made up of two components, the conventional GCTB component and the malignant component. The Ki67 labeling index was higher in the malignant components of SMGCTB and metastatic lesions compared with that in primary and recurrent conventional GCTB, or the conventional GCTB component of SMGCTB. Moreover, p53 expression was higher in these same components in patients who underwent curettage and bone grafting; however, there was no difference in the patient that received denosumab treatment. In this patient, clinical cancer genomic profiling revealed loss of CDKN2A, CDKN2B and MTAP expression. All three patients developed distant metastasis. The patients with SMGCTB in the ulna and femur died 13 and 54 months after detection of malignant transformation, respectively. The patient with SMGCTB in the sacrum received carbon-ion radiotherapy to the sacrum and pazopanib; the treatment was effective and the patient was alive at the last follow-up 3 years later. In conclusion, p53 may be associated with malignant transformation in GCTB. Future studies should investigate the association of between denosumab treatment and malignant transformation, as well as molecular targeted therapy to improve the clinical outcomes of SMGCTB.

DOI： 10.3892/ol.2022.13439

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骨・軟部肉腫に対するがんゲノムプロファイリング検査から検出されるpresumed germline pathogenic variantsの意義

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1770 - S1770 2022.9

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