Kanaji, Arihiko



School of Medicine, Department of Orthopaedic Surgery (Shinanomachi)


Assistant Professor/Senior Assistant Professor

Career 【 Display / hide

  • 1994.05


  • 1995.06


  • 1996.04


  • 1996.05


  • 1997.07

    慶應義塾大学助手(整形外科) 慶應義塾大学月ヶ瀬リハビリテ-ションセンタ-出向

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Academic Background 【 Display / hide

  • 1985.04


  • 1988.04



Academic Degrees 【 Display / hide

  • 医学博士, Keio University, Dissertation, 2004.05

    Improvement of skeletal lesions in mice with mucopolysaccharidosis type VII by neonatal adenoviral gene transfer. Mol Ther. 8(5):718-25, 2003


Papers 【 Display / hide

  • Bcl6 promotes osteoblastogenesis through stat1 inhibition

    Fujie Atsuhiro, Funayama Atsushi, Miyauchi Yoshiteru, Sato Yuiko, Kobayashi Tami, Kanagawa Hiroya, Katsuyama Eri, Hao Wu, Tando Toshimi, Watanabe Ryuichi, Morita Mayu, Miyamoto Kana, Kanaji Arihiko, Morioka Hideo, Matsumoto Morio, Toyama Yoshiaki, Miyamoto Takeshi

    Biochemical and Biophysical Research Communications 457 ( 3 ) 451 - 456 2015.02

    ISSN  0006-291X

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    <p>Bone mass is tightly controlled by a balance between osteoclast and osteoblast activities. Although these cell types mature via different pathways, some factors reportedly regulate differentiation of both. Here, in a search for factors governing osteoblastogenesis but also expressed in osteoclasts to control both cell types by one molecule, we identified B cell lymphoma 6 (Bcl6) as one of those factors and show that it promotes osteoblast differentiation. Bcl6 was previously shown to negatively regulate osteoclastogenesis. We report that lack of Bcl6 results in significant inhibition of osteoblastogensis in vivo and in vitro and in defects in secondary ossification center formation in vivo. Signal transducer and activator of transcription 1 (Stat1) reportedly attenuates osteoblast differentiation by inhibiting nuclear translocation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation. We found that lack of Bcl6 resulted in signifi cant elevation of Stat1 mRNA and protein expression in osteoblasts and showed that Stat1 is a direct target of Bcl6 using a chromatin immune-precipitation assay. Mice lacking both Bcl6 and Stat1 (DKO) exhibited significant rescue of bone mass and osteoblastic parameters as well as partial rescue of secondary ossification center formation compared with Bcl6-de ficient mice in vivo. Altered osteoblastogenesis in Bcl6-defi cient cells was also restored in DKO in vitro. Thus, Bcl6 plays crucial roles in regulating both osteoblast activation and osteoclast inhibition.</p>

  • ADAM17 regulates IL-1 signaling by selectively releasing IL-1 receptor type 2 from the cell surface

    Uchikawa Shinichi, Yoda Masaki, Tohmonda Takahide, Kanaji Arihiko, Matsumoto Morio, Toyama Yoshiaki, Horiuchi Keisuke

    Cytokine 71 ( 2 ) 238 - 245 2015.02

    ISSN  1043-4666

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    <p>Interleukin (IL)-1 is one of the most evolutionarily conserved cytokines and plays an essential role in the regulation of innate immunity. IL-1 binds to two different receptors, IL-1R1 and IL-1R2, which share approximately 28% amino acid homology. IL-1R1 contains a cytoplasmic domain and is capable of transducing cellular signals; by contrast, IL-1R2 lacks a functional cytoplasmic domain and serves as a decoy receptor for IL-1. Interestingly, IL-1R2 is proteolytically cleaved and also functions as a soluble receptor that blocks IL-1 activity. In the present study, we examined the shedding properties of IL-1R2 and demonstrate that ADAM17 is de facto the major sheddase for IL-1R2 and that introducing a mutation into the juxta-membrane domain of IL-1R2 significantly desensitizes IL-1R2 to proteolytic cleavage. IL-1R1 was almost insensitive to ADAM17-dependent cleavage; however, the replacement of the juxta-membrane domain of IL-R1 with that of IL-1R2 significantly increased the sensitivity of IL-1R1 to shedding. Furthermore, we demonstrate that ADAM17 indirectly enhances IL-1 signaling in a cell-autonomous manner by selectively cleaving IL-1R2. Taken together, the data collected in the present study indicate that ADAM17 affects sensitivity to IL-1 by changing the balance between IL-1R1 and the decoy receptor IL-1R2.</p>

  • Cytotoxic effects of cobalt and nickel ions on osteocytes in vitro

    Kanaji Arihiko, Orhue Vbenosawemwinghaye, Caicedo Marco S., Virdi Amarjit S., Sumner Dale R., Hallab Nadim J., Yoshiaki Toyama, Sena Kotaro

    Journal of Orthopaedic Surgery and Research 9 ( 1 )  2014.10

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    <p>Background: Metal-on-metal prostheses undergo wear and corrosion, releasing soluble ions and wear particles into the surrounding environment. Reports described early failures of the metal-on-metal prostheses, with histologic features similar to a Type IV immune response. Mechanisms by which metal wear products and metal ion causing this reaction are not completely understood, and the effects of metal ions on osteocytes, which represent more than 95% of all the bone cells, have not been also studied. We hypothesized that soluble metal ions released from the cobalt-chromium-molybdenum (Co-Cr-Mo) prosthesis may have cytotoxic effect on osteocytes.Methods: MLO-Y4 osteocytes were treated with various metal ion solutions for 24 and 48 h. The effect of ion treatment on cytotoxicity was assessed by WST-1 reagents and cell death ELISA. Morphological changes were analyzed by a phase-contrast microscope or fluorescent microscope using Hoechst 33342 and propidium iodine staining.Results: Cr and Mo ions did not cause cell death under 0.50 mM, highest concentration studied, whereas Co and Ni ions had significant cytotoxic effect on MLO-Y4 cells at concentrations grater than 0.10 mM and at 0.50 mM, respectively, in a dose-dependent manner. According to the ELISA data, osteocytes treated with Co ions were more susceptible to necrotic than apoptotic cell death, while Ni ions caused osteocyte apoptosis. The morphological assays show that cells treated with Co and Ni ions at high concentration were fewer in number and rounded. In addition, fluorescent images showed a marked reduction in live cells and an increase in dead osteocytes treated with Co and Ni ions at high concentration.Conclusions: Metal ions released from metal-on-metal bearing surfaces have potentially cytotoxic effects on MLO-Y4 osteocytes, in vitro.</p>

  • Experimental assessment of a novel intramedullary nail for callus distraction by the segmental bone transport method

    Yamaguchi Kenji, Yanagimoto Shigeru, Kageyama Toshiaki, Fujita Yoshinari, Funayama Atsushi, Kanaji Arihiko, Susa Michiro, Toyama Yoshiaki

    Journal of Orthopaedic Science 19 ( 2 ) 323 - 331 2014

    ISSN  0949-2658

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    <p>Background: Segmental bone transport (SBT) is a revolutionary method for treating extensive bone defects, and it is in wide clinical use. Although external fixation is generally used to perform SBT, it is associated with problems such as complications due to pin placement and limitations of the amount and rate of lengthening. As a way to overcome these problems we developed a novel intramedullary (IM) nail for SBT that minimizes damage to the surrounding tissue and improves the amount and rate of bone lengthening. The purpose of this study was to perform SBT in the femur of beagle dogs using the novel IM nail that we devised, and to evaluate the morphology and quality of the regenerated bone and circulation status in the surrounding tissue. We also considered the possibilities and limitations of the IM in regard to clinical application. Methods: This experiment was conducted on six beagle dogs. The novel IM nail we devised was inserted into the marrow cavity of the femur, and a 30-mm bone defect was created. After a 7-day postoperative waiting period, a bone segment was transported by 1.0 mm per day in two 0.5-mm increments. Because the nail broke in two dogs, they received only partial elongation by 15 mm over a 15-day period, with a 15-mm defect remaining, whereas full elongation by 30 mm in 30 days was performed in the other four dogs. The elongation was followed by a 30-day bone hardening period. Results: The macroscopic and histological results demonstrated that high-quality, new bone had replaced the 30-mm bone defect created in the femur of all six dogs. The density and number of blood vessels that had penetrated the elongated segment of bone from the surrounding muscles was greater than in the corresponding segment of the contralateral femur, which served as a control. The results imply that the traction stimulus induced vigorous angiogenesis in the surrounding tissue. Conclusion: We concluded that this method has tremendous potential for clinical application, and will overcome the limitations of conventional external fixators. © 2014 The Japanese Orthopaedic Association.</p>

  • Crowe type IV dislocated hip treated by total hip arthroplasty with subtrochanteric step-cut femoral shortening osteotomy and Wagner cone stem

    Nishio Makoto, Kanaji Arihiko, Horiuchi Keisuke, Funayama Atsushi, Oishi Teruyo, Toyama Yoshiaki, Yamada Harumoto

    Current Orthopaedic Practice 24 ( 5 ) 552 - 556 2013.09

    ISSN  1940-7041

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Papers, etc., Registered in KOARA 【 Display / hide

Research Projects of Competitive Funds, etc. 【 Display / hide

  • Smadを標的とした不動性筋萎縮治療法の開発


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 金治 有彦, Grant-in-Aid for Scientific Research (C), Principal Investigator


Courses Taught 【 Display / hide



Courses Previously Taught 【 Display / hide

  • 小児の運動器疾患と外傷

    Keio University, 2015