Updated on 2022/05/13

写真a

 
MATSUSHITA Masaki
 
Organization
Nagoya University Hospital Orthopedics Lecturer of hospital
Title
Lecturer of hospital

Degree 1

  1. 博士(医学) ( 2014.3   名古屋大学 ) 

Current Research Project and SDGs 1

  1. ドッラグ・リポジショニングによる軟骨無形成症治療薬の開発研究

Research History 4

  1. 名古屋大学附属病院整形外科医員

    2013.4 - 2014.3

      More details

    Country:Japan

  2. あいち小児保健医療総合センター整形外科

    2010.4 - 2011.4

      More details

    Country:Japan

  3. 社会保険中京病院整形外科

    2004.4 - 2010.3

      More details

    Country:Japan

  4. 社会保険中京病院嘱託研修医

    2002.5 - 2004.3

      More details

    Country:Japan

Education 2

  1. Nagoya University   Graduate School, Division of Medical Sciences

    2010.4 - 2014.3

      More details

    Country: Japan

  2. Nagoya University   Faculty of Medicine

    1996.4 - 2002.3

      More details

    Country: Japan

Professional Memberships 5

  1. 日本整形外科学会

  2. 日本小児整形外科学会

  3. 中部日本整形外科災害外科学会

  4. 日本骨代謝学会

  5. 日本軟骨代謝学会

Awards 3

  1. 第21回日本軟骨代謝学会賞

    2016   日本軟骨代謝学会  

     More details

    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  2. New Investigator Award of 7th International Conference on Children Bone health (ICCBH) 2015

    2015   International Conference on Children Bone health (ICCBH)  

     More details

    Award type:Award from international society, conference, symposium, etc.  Country:Austria

  3. Basic Science Award Paper of Pediatric Orthopaedic Society of North America (POSNA) Annual Meeting 2015

    2015   Pediatric Orthopaedic Society of North America (POSNA)  

     More details

    Award type:Award from international society, conference, symposium, etc.  Country:United States

 

Papers 57

  1. Predictive ability of inflammatory markers and laboratory parameters in Legg-Calvé-Perthes disease: A single-center retrospective comparative study.

    Mishima K, Kamiya Y, Matsushita M, Imagama S, Kitoh H

    Medicine   Vol. 101 ( 11 )   2022.3

     More details

    Language:English  

    DOI: 10.1097/MD.0000000000029061

    PubMed

  2. Disease-specific complications and multidisciplinary interventions in achondroplasia

    Kitoh Hiroshi, Matsushita Masaki, Mishima Kenichi, Kamiya Yasunari, Sawamura Kenta

    JOURNAL OF BONE AND MINERAL METABOLISM   Vol. 40 ( 2 ) page: 189 - 195   2022.3

     More details

  3. Guided growth for coronal lower limb deformities in skeletal dysplasia.

    Kitoh H, Kamiya Y, Mishima K, Matsushita M, Kaneko H, Kitamura A, Sawamura K, Matsuyama S

    Journal of pediatric orthopedics. Part B     2022.2

     More details

    Language:English  

    DOI: 10.1097/BPB.0000000000000965

    PubMed

  4. Meclozine ameliorates skeletal muscle pathology and increases muscle forces in mdx mice

    Kawamura Yusuke, Hida Tetsuro, Ohkawara Bisei, Matsushita Masaki, Kobayashi Takeshi, Ishizuka Shinya, Hiraiwa Hideki, Tanaka Satoshi, Tsushima Mikito, Nakashima Hiroaki, Ito Kenyu, Imagama Shiro, Ito Mikako, Masuda Akio, Ishiguro Naoki, Ohno Kinji

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 592   page: 87 - 92   2022.2

     More details

  5. Meclozine Attenuates the MARK Pathway in Mammalian Chondrocytes and Ameliorates FGF2-Induced Bone Hyperossification in Larval Zebrafish

    Takemoto Genta, Matsushita Masaki, Okamoto Takaaki, Ito Toshinari, Matsuura Yuki, Takashima Chieko, Chen-Yoshikawa Toyofumi Fengshi, Ebi Hiromichi, Imagama Shiro, Kitoh Hiroshi, Ohno Kinji, Hosono Yasuyuki

    FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY   Vol. 9   page: 694018   2022.1

     More details

  6. Bypass of Epiphyseal Fragmentation Following Early Salter Innominate Osteotomy and Its Clinical Relevance in Legg-Calve-Perthes Disease

    Mishima Kenichi, Kamiya Yasunari, Matsushita Masaki, Imagama Shiro, Kitoh Hiroshi

    JOURNAL OF PEDIATRIC ORTHOPAEDICS   Vol. 42 ( 5 ) page: 239 - 245   2022

     More details

  7. Inconvenience and adaptation in Japanese adult achondroplasia and hypochondroplasia: A cross-sectional study.

    Ajimi A, Matsushita M, Mishima K, Haga N, Fujiwara S, Ozono K, Kubota T, Kitaoka T, Imagama S, Kitoh H

    Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology   Vol. 31 ( 1 ) page: 18 - 24   2022

     More details

    Language:English  

    DOI: 10.1297/cpe.2021-0043

    PubMed

  8. A cross-sectional nationwide survey of osteosclerotic skeletal dysplasias in Japan.

    Sawamura K, Mishima K, Matsushita M, Kamiya Y, Kitoh H

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association     2021.7

     More details

    Language:English  

    DOI: 10.1016/j.jos.2021.05.012

    PubMed

  9. Asfotase alfa has a limited effect in improving the bowed limbs in perinatal benign hypophosphatasia: A case report

    Matsushita Masaki, Mishima Kenichi, Nagata Tadashi, Kamiya Yasunari, Imagama Shiro, Kitoh Hiroshi

    CLINICAL PEDIATRIC ENDOCRINOLOGY   Vol. 30 ( 1 ) page: 53 - 56   2021.1

     More details

  10. Health-related Quality of Life in Adult Patients with Multiple Epiphyseal Dysplasia and Spondyloepiphyseal Dysplasia.

    Matsushita M, Mishima K, Kamiya Y, Haga N, Fujiwara S, Ozono K, Kubota T, Kitaoka T, Imagama S, Kitoh H

    Progress in rehabilitation medicine   Vol. 6   page: 20210048   2021

     More details

    Language:English  

    DOI: 10.2490/prm.20210048

    PubMed

  11. Effect of periosteal resection on longitudinal bone growth in a mouse model of achondroplasia

    Kaneko Shinya, Matsushita Masaki, Mishima Kenichi, Takegami Yasuhiko, Imagama Shiro, Kitoh Hiroshi

    BONE REPORTS   Vol. 13   page: 100708   2020.12

     More details

  12. Legg-Calve-Perthes disease in a patient with Bardet-Biedl syndrome: A case report of a novel MKKS/BBS6 mutation

    Mishima Kenichi, Fujita Atsushi, Mizuno Seiji, Matsushita Masaki, Nagata Tadashi, Kamiya Yasunari, Miyake Noriko, Matsumoto Naomichi, Imagama Shiro, Kitoh Hiroshi

    CLINICAL CASE REPORTS   Vol. 8 ( 12 ) page: 3109 - 3114   2020.12

     More details

  13. Comparison of surgical and nonsurgical containment methods for patients with Legg-Calve-Perthes disease of the onset ages between 6.0 and 8.0 years: Salter osteotomy versus a non-weight-bearing hip flexion-abduction brace

    Kaneko Hiroshi, Kitoh Hiroshi, Mishima Kenichi, Matsushita Masaki, Hattori Tadashi, Noritake Koji, Ishiguro Naoki, Yoshihashi Yuji

    JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B   Vol. 29 ( 6 ) page: 542 - 549   2020.11

     More details

  14. A retrospective comparative study of corrective osteotomy for tibial deformities with the multiaxial correction fixator and the circular fixator.

    Matsushita M, Kitoh H, Mishima K, Nagata T, Kamiya Y, Kaneko H, Hattori T, Ishiguro N

    Journal of clinical orthopaedics and trauma   Vol. 11 ( Suppl 4 ) page: S621 - S625   2020.7

     More details

    Language:English  

    DOI: 10.1016/j.jcot.2020.05.004

    PubMed

  15. Lower limb pain following allogeneic hematopoietic stem cell transplantation in Japanese children

    Mishima Kenichi, Kitoh Hiroshi, Matsushita Masaki, Nagata Tadashi, Kamiya Yasunari, Takahashi Yoshiyuki, Ishiguro Naoki

    JOURNAL OF ORTHOPAEDIC SCIENCE   Vol. 25 ( 4 ) page: 682 - 687   2020.7

     More details

  16. Pharmacokinetics and safety after once and twice a day doses of meclizine hydrochloride administered to children with achondroplasia

    Kitoh Hiroshi, Matsushita Masaki, Mishima Kenichi, Nagata Tadashi, Kamiya Yasunari, Ueda Kohei, Kuwatsuka Yachiyo, Morikawa Hiroshi, Nakai Yasuhiro, Ishiguro Naoki

    PLOS ONE   Vol. 15 ( 4 ) page: e0229639   2020.4

     More details

  17. Severe achondroplasia due to two de novo variants in the transmembrane domain of FGFR3 on the same allele: A case report

    Nagata Tadashi, Matsushita Masaki, Mishima Kenichi, Kamiya Yasunari, Kato Kohji, Toyama Miho, Ogi Tomoo, Ishiguro Naoki, Kitoh Hiroshi

    MOLECULAR GENETICS & GENOMIC MEDICINE   Vol. 8 ( 3 ) page: e1148   2020.3

     More details

  18. Impact of fracture characteristics and disease-specific complications on health-related quality of life in osteogenesis imperfecta

    Matsushita Masaki, Mishima Kenichi, Yamashita Satoshi, Haga Nobuhiko, Fujiwara Sayaka, Ozono Keiichi, Kubota Takuo, Kitaoka Taichi, Ishiguro Naoki, Kitoh Hiroshi

    JOURNAL OF BONE AND MINERAL METABOLISM   Vol. 38 ( 1 ) page: 109 - 116   2020.1

     More details

  19. Physical, Mental, and Social Problems of Adolescent and Adult Patients with Achondroplasia

    Matsushita Masaki, Kitoh Hiroshi, Mishima Kenichi, Yamashita Satoshi, Haga Nobuhiko, Fujiwara Sayaka, Ozono Keiichi, Kubota Takuo, Kitaoka Taichi, Ishiguro Naoki

    CALCIFIED TISSUE INTERNATIONAL   Vol. 104 ( 4 ) page: 364 - 372   2019.4

     More details

  20. Early radiographic risk factors for rigid relapse in idiopathic clubfoot treated with the Ponseti method.

    Mishima K, Kitoh H, Matsushita M, Sugiura H, Hasegawa S, Kitamura A, Nishida Y, Ishiguro N

    Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons   Vol. 24 ( 6 ) page: 509 - 513   2018.12

     More details

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

    DOI: 10.1016/j.fas.2017.06.003

    Web of Science

    PubMed

  21. Changes in the range of motion of the lower limb joints during extensive tibial lengthening in achondroplasia

    Kadono Izumi, Kitoh Hiroshi, Mishima Kenichi, Matsushita Masaki, Sato Koji, Kako Masato, Ishiguro Naoki

    JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B   Vol. 27 ( 6 ) page: 535-540   2018.11

     More details

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

    DOI: 10.1097/BPB.0000000000000526

    Web of Science

    PubMed

  22. A Mouse Distraction Osteogenesis Model

    Fujio Masahito, Osawa Yusuke, Matsushita Masaki, Ogisu Kota, Tsuchiya Shuhei, Kitoh Hiroshi, Hibi Hideharu

    JOVE-JOURNAL OF VISUALIZED EXPERIMENTS   ( 141 )   2018.11

     More details

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

    DOI: 10.3791/57925

    Web of Science

    PubMed

  23. Long term health-related quality of life in patients with achondroplasia and hypochondroplasia

    Matsushita Masaki, Kitoh Hiroshi, Mishima Kenichi, Ishiguro Naoki, Fujiwara Sayaka, Haga Nobuhiko, Kitaoka Taichi, Kubota Takuo, Ozono Keiichi

    JOURNAL OF BONE AND MINERAL RESEARCH   Vol. 33   page: 300 - 301   2018.11

     More details

    Language:Japanese  

    Web of Science

  24. Activated FGFR3 prevents subchondral bone sclerosis during the development of osteoarthritis in transgenic mice with achondroplasia.

    Okura T, Matsushita M, Mishima K, Esaki R, Seki T, Ishiguro N, Kitoh H

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society   Vol. 36 ( 1 ) page: 300 - 308   2018.1

     More details

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

    DOI: 10.1002/jor.23608

    Web of Science

    PubMed

  25. Chronic lateral epiphyseal separation of the proximal tibia causes late-onset tibia vara.

    Hasegawa S, Kitoh H, Matsushita M, Mishima K, Kadono I, Sugiura H, Kitamura A, Ishiguro N

    Journal of pediatric orthopedics. Part B   Vol. 27 ( 1 ) page: 31 - 34   2018.1

     More details

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

    DOI: 10.1097/BPB.0000000000000430

    Web of Science

    PubMed

  26. A Novel Heterozygous Mutation in the T-box Protein 4 Gene in an Adult Case of Small Patella Syndrome.

    Oda T, Matsushita M, Ono Y, Kitoh H, Sakai T

    Journal of orthopaedic case reports   Vol. 8 ( 1 ) page: 85 - 88   2018.1

     More details

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

    DOI: 10.13107/jocr.2250-0685.1012

    PubMed

  27. Extensive Bone Lengthening for a Patient with Linear Morphea.

    Mishima K, Kitoh H, Matsushita M, Nagata T, Kamiya Y, Ishiguro N

    Case reports in orthopedics   Vol. 2018   page: 4535804   2018

     More details

    Language:English  

    DOI: 10.1155/2018/4535804

    PubMed

  28. Activated FGFR3 promotes bone formation via accelerating endochondral ossification in mouse model of distraction osteogenesis

    Osawa Yusuke, Matsushita Masaki, Hasegawa Sachi, Esaki Ryusaku, Fujio Masahito, Ohkawara Bisei, Ishiguro Naoki, Ohno Kinji, Kitoh Hiroshi

    BONE   Vol. 105   page: 42-49   2017.12

     More details

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

    DOI: 10.1016/j.bone.2017.05.016

    Web of Science

    PubMed

  29. Activated FGFR3 Prevents Subchondral Bone Sclerosis During the Development of Osteoarthritis in Transgenic Mice with Achondroplasia.

    Okura Toshiaki, Matsushita Masaki, Mishima Kenichi, Seki Taisuke, Ishiguro Naoki, Kitoh Hiroshi

    JOURNAL OF BONE AND MINERAL RESEARCH   Vol. 32   page: S201 - S201   2017.12

     More details

    Language:Japanese  

    Web of Science

  30. Clinical dosage of meclozine promotes longitudinal bone growth, bone volume, and trabecular bone quality in transgenic mice with achondroplasia

    Matsushita Masaki, Esaki Ryusaku, Mishima Kenichi, Ishiguro Naoki, Ohno Kinji, Kitoh Hiroshi

    SCIENTIFIC REPORTS   Vol. 7 ( 1 ) page: 7371   2017.8

     More details

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

    DOI: 10.1038/s41598-017-07044-8

    Web of Science

    PubMed

  31. Percutaneous pinning after prolonged skeletal traction with the hip in a flexed position for unstable slipped capital femoral epiphysis A case series of 11 patients

    Matsushita Masaki, Mishima Kenichi, Iwata Kohji, Hattori Tadashi, Ishiguro Naoki, Kitoh Hiroshi

    MEDICINE   Vol. 96 ( 19 ) page: e6662   2017.5

     More details

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

    DOI: 10.1097/MD.0000000000006662

    Web of Science

    PubMed

  32. Is the timing of surgery associated with avascular necrosis after unstable slipped capital femoral epiphysis? A multicenter study.

    Kohno Yusuke, Nakashima Yasuharu, Kitano Toshio, Irie Taichi, Kita Atsushi, Nakamura Tomoyuki, Endo Hirosuke, Fujii Yosuke, Kuroda Takayuki, Mitani Shigeru, Kitoh Hiroshi, Matsushita Masaki, Hattori Tadashi, Iwata Koji, Iwamoto Yukihide

    JOURNAL OF ORTHOPAEDIC SCIENCE   Vol. 22 ( 1 ) page: 112-115   2017.1

     More details

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

    DOI: 10.1016/j.jos.2016.08.012

    Web of Science

    PubMed

  33. Maternal administration of meclozine for the treatment of foramen magnum stenosis in transgenic mice with achondroplasia

    Matsushita Masaki, Mishima Kenichi, Esaki Ryusaku, Ishiguro Naoki, Ohno Kinji, Kitoh Hiroshi

    JOURNAL OF NEUROSURGERY-PEDIATRICS   Vol. 19 ( 1 ) page: 91-95   2017.1

     More details

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

    DOI: 10.3171/2016.7.PEDS16199

    Web of Science

    PubMed

  34. Maternal administration of meclozine for the treatment of foramen magnum stenosis in transgenic mice with achondroplasia

    Matsushita M, Mishima K, Esaki R, Ishiguro N, Ohno K, Kitoh H

    J Neurosurg Pediatr   Vol. 19   page: 91-95   2017

     More details

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

  35. Clinical Results and Complications of Lower Limb Lengthening for Fibular Hemimelia: A Report of Eight Cases. Invited Reviewed

    Mishima K, Kitoh H, Iwata K, Matsushita M, Nishida Y, Hattori T, Ishiguro N

    Medicine (Baltimore)   Vol. 95 ( 21 ) page: e3787   2016.5

     More details

  36. Tranilast stimulates endochondral ossification by upregulating SOX9 and RUNX2 promoters Invited Reviewed

    Hasegawa S, Kitoh H, Ohkawara B, Mishima K, Matsushita M, Masuda A, Ishiguro N, Ohno K

    Biochem Biophys Res Commun   Vol. 470 ( 2 ) page: 356 - 361   2016.2

     More details

  37. Characterisation of novel RUNX2 mutation with alanine tract expansion from Japanese cleidocranial dysplasia patient Invited Reviewed

    Shibata A, Machida J, Yamaguchi S, Kimura M, Tatematsu T, Miyachi H, Matsushita M, Kitoh H, Ishiguro N, Nakayama A, Higashi Y, Shimozato K, Tokita Y

    Mutagenesis   Vol. 31 ( 1 ) page: 61 - 67   2016.1

     More details

  38. Low bone mineral density in achondroplasia and hypochondroplasia Reviewed

    Matsushita M, Kitoh H, Mishima K, Kadono I, Sugiura H, Hasegawa S, Nishida Y, Ishiguro N

    Pediatr Int     page: 10.1111/ped.12890   2016

     More details

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

    DOI: 10.1111/ped.12890

  39. Prediction of Clinically Significant Leg-Length Discrepancy in Congenital Disorders Invited Reviewed

    Mishima K, Kitoh H, Kadono I, Matsushita M, Sugiura H, Hasegawa S, Kitamura A, Nishida Y, Ishiguro N

    Orthopedics   Vol. 38 ( 10 ) page: e919 - e924   2015.10

     More details

  40. A glutamine repeat variant of the RUNX2 gene causes cleidocranial dysplasia Reviewed

    Matsushita M, Kitoh H, Subasioglu A, Colak FK, Dundar M, Mishima K, Nishida Y, Ishiguro N

    Mol Syndromol     page: in press   2015

     More details

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

  41. Meclozine promotes lomgitudinal skeletal growth in transgenic mice with achondroplasia carrying a gain-of-function mutation in the FGFR3 gene Reviewed

    Matsushita M, Hasegawa S, Kitoh H, Mori K, Ohkawara B, Yasoda A, Masuda A, Ishiguro N, Ohno K

    Endocrinology   Vol. 156   page: 548-554   2015

     More details

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

  42. Factors associated with an unfavourable outcome after Salter innominate osteotomy in patients with unilateral developmental dysplasia of the hip: Does occult dysplasia of the contralateral hip affect the outcome? Invited Reviewed

    Kaneko H, Kitoh H, Mishima K, Matsushita M, Kadono I, Ishiguro N, Hattori T

    Bone Joint J   Vol. 96-B ( 10 ) page: 1419 - 1423   2014.10

     More details

  43. Early and late fracture following extensive limb lengthening in achondroplasia and hypochondroplasia Invited Reviewed

    Kitoh H, Kaneko H, Mishima K, Matsushita M, Kadono I, Nishida Y, Ishiguro N

    Bone Joint J   Vol. 96-B ( 9 ) page: 1269 - 1273   2014.9

     More details

  44. Radiographic characteristics of the hand and cervical spine in fibrodysplasia ossificans progressiva Invited Reviewed

    Mishima K, Kitoh H, Haga N, Nakashima Y, Kamizono J, Katagiri T, Susami T, Matsushita M, Ishiguro N

    Intractable Rare Dis Res   Vol. 3 ( 2 ) page: 46 - 51   2014.5

     More details

  45. A novel in-flame deletion of the RUNX2 gene causes a classic form of cleidocranial dysplasia Reviewed

    Matsushita M, Kitoh H, Kaneko H, Mishima K, Itoh Y, Tokita Y, Ishiguro N

    J Bone Miner Metab   Vol. 32   page: 96-99   2014

     More details

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

  46. Benign prenatal hypophosphatasia: a treatable disease not to be missed Reviewed

    Matsushita M, Kitoh H, Michigami T, Tachikawa K, Kaneko H, Mishima K, Ishiguro N

    Ped Radiol   Vol. 44   page: 340-343   2014

     More details

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

  47. A case of severe proximal focal femoral deficiency with overlapping phenotypes of Al-Awadi-Raas-Rothschild syndrome and Fuhrmann syndrome Reviewed

    Matsushita M, Kitoh H, Mishima K, Nishida Y, Ishiguro N

    Ped Radiol   Vol. 44   page: 1617-1619   2014

     More details

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

  48. A comparative study of blade plate fixation and external fixation in osteotomies for slipped capital femoral epiphysis Invited Reviewed

    Kitoh H, Kitakoji T, Hattori T, Kaneko H, Mishima K, Matsushita M, Ishiguro N

    J Pediatr Orthop B   Vol. 22 ( 6 ) page: 542 - 547   2013.11

     More details

  49. Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial Invited Reviewed

    Kitoh H, Achiwa M, Kaneko H, Mishima K, Matsushita M, Kadono I, Horowitz JD, Sallustio BC, Ohno K, Ishiguro N

    Orphanet J Rare Dis   Vol. 8   page: 163   2013.10

     More details

  50. Long-term outcome of gradual reduction using overhead traction for developmental dysplasia of the hip over 6 months of age Invited Reviewed

    Kaneko H, Kitoh H, Mishima K, Matsushita M, Ishiguro N

    J Pediatr Orthop   Vol. 33 ( 6 ) page: 628 - 634   2013.9

     More details

  51. Prognostic factors for trochanteric overgrowth after containment treatment in Legg-Calvé-Perthes disease Invited Reviewed

    Kitoh H, Kaneko H, Mishima K, Matsushita M, Ishiguro N

    J Pediatr Orthop B   Vol. 22 ( 5 ) page: 432 - 436   2013.9

     More details

  52. Clinically applicable antianginal agents suppress osteoblastic transformation of myogenic cells and heterotopic ossifications in mice Invited Reviewed

    Yamamoto R, Matsushita M, Kitoh H, Masuda A, Ito M, Katagiri T, Kawai T, Ishiguro N, Ohno K

    J Bone Miner Metab   Vol. 31 ( 1 ) page: 26 - 33   2013.1

     More details

  53. Meclozine facilitates chondrocyte proliferation and differentiation by attenuating abnormally activated fibroblast growth factor receptor 3 (FGFR3) signaling in achondroplasia Reviewed

    Matsushita M, Kitoh H, Ohkawara B, Mishima K, Kaneko H, Ito M, Masuda A, Ishiguro N, Ohno K

    PLoS One   Vol. 8   page: e81569   2013

     More details

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

  54. A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild campomelic dysplasia and small patella syndrome Reviewed

    Matsushita M, Kitoh H, Kaneko H, Mishima K, Kadono I, Ishiguro N, Nishmura G

    Am J Med Genet A   Vol. 161   page: 2528-2534   2013

     More details

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

  55. Orthopaedic manifestations and diagnostic clues in children with Guillain-Barré syndrome Reviewed

    Matsushita M, Kitoh H, Itomi K, Kitakoji T, Iwata K, Mishima K, Ishiguro N, Hattori T

    J Child Orthop   Vol. 7   page: 177-182   2013

     More details

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

  56. Isolated bifid rib: clinical and radiological findings in children Invited Reviewed

    Kaneko H, Kitoh H, Mabuchi A, Mishima K, Matsushita M, Ishiguro N

    Pediatr Int   Vol. 54 ( 6 ) page: 820 - 823   2012.12

     More details

  57. Novel compound heterozygous mutations in the cathepsin K gene in Japanese female siblings with pyknodysostosis Reviewed

    Matsushita M, Kitoh H, Kaneko H, Mishima K, Itoh Y, Hattori T, Ishiguro N

    Mol Syndromol   Vol. 2   page: 254-258   2012

     More details

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

▼display all

Books 3

  1. 今日の整形外科治療指針第8版

    松下雅樹( Role: Contributor ,  FGFR3軟骨異形成症グループ)

    医学書院  2021.10 

     More details

    Language:Japanese

  2. 整形・災害外科(特集:小児整形外科の最新知見)

    松下雅樹、鬼頭浩史( Role: Contributor ,  軟骨無形成症に対する治療の現状と薬物療法の可能性)

    金原出版株式会社  2019 

     More details

    Language:Japanese

  3. 雑誌「小児内科」増刊号:小児疾患の診断治療基準 改訂5版(第2部:疾患 XIX.運動器疾患)

    松下雅樹( Role: Contributor ,  393.軟骨無形成症)

    株式会社東京医学社  2018 

     More details

    Language:Japanese

MISC 19

  1. Extensive Bone Lengthening for a Patient with Linear Morphea. Reviewed

    Mishima K, Kitoh H, Matsushita M, Nagata T, Kamiya Y, Ishiguro N

    Case reports in orthopedics   Vol. 2018   page: 4535804   2018

     More details

    Language:English  

    DOI: 10.1155/2018/4535804

    PubMed

  2. Clinical Results and Complications of Lower Limb Lengthening for Fibular Hemimelia: A Report of Eight Cases. Reviewed

    Mishima K, Kitoh H, Iwata K, Matsushita M, Nishida Y, Hattori T, Ishiguro N

    Medicine   Vol. 95 ( 21 ) page: e3787   2016.5

     More details

    Language:English  

    DOI: 10.1097/MD.0000000000003787

    PubMed

  3. Tranilast stimulates endochondral ossification by upregulating SOX9 and RUNX2 promoters. Reviewed

    Hasegawa S, Kitoh H, Ohkawara B, Mishima K, Matsushita M, Masuda A, Ishiguro N, Ohno K

    Biochemical and biophysical research communications   Vol. 470 ( 2 ) page: 356-361   2016.2

     More details

    Language:English  

    DOI: 10.1016/j.bbrc.2016.01.044

    PubMed

  4. Characterisation of novel RUNX2 mutation with alanine tract expansion from Japanese cleidocranial dysplasia patient. Reviewed

    Shibata A, Machida J, Yamaguchi S, Kimura M, Tatematsu T, Miyachi H, Matsushita M, Kitoh H, Ishiguro N, Nakayama A, Higashi Y, Shimozato K, Tokita Y

    Mutagenesis   Vol. 31 ( 1 ) page: 61-7   2016.1

     More details

    Language:English  

    DOI: 10.1093/mutage/gev057

    PubMed

  5. Prediction of Clinically Significant Leg-Length Discrepancy in Congenital Disorders. Reviewed

    Mishima K, Kitoh H, Kadono I, Matsushita M, Sugiura H, Hasegawa S, Kitamura A, Nishida Y, Ishiguro N

    Orthopedics   Vol. 38 ( 10 ) page: e919-24   2015.10

     More details

    Language:English  

    DOI: 10.3928/01477447-20151002-60

    PubMed

  6. Meclozine promotes longitudinal skeletal growth in transgenic mice with achondroplasia carrying a gain-of-function mutation in the FGFR3 gene. Reviewed

    Matsushita M, Hasegawa S, Kitoh H, Mori K, Ohkawara B, Yasoda A, Masuda A, Ishiguro N, Ohno K

    Endocrinology   Vol. 156 ( 2 ) page: 548-54   2015.2

     More details

    Language:English  

    DOI: 10.1210/en.2014-1914

    PubMed

  7. A case of severe proximal focal femoral deficiency with overlapping phenotypes of Al-Awadi-Raas-Rothschild syndrome and Fuhrmann syndrome. Reviewed

    Matsushita M, Kitoh H, Mishima K, Nishida Y, Ishiguro N

    Pediatric radiology   Vol. 44 ( 12 ) page: 1617-9   2014.12

     More details

    Language:English  

    DOI: 10.1007/s00247-014-3013-1

    PubMed

  8. Radiographic characteristics of the hand and cervical spine in fibrodysplasia ossificans progressiva. Reviewed

    Mishima K, Kitoh H, Haga N, Nakashima Y, Kamizono J, Katagiri T, Susami T, Matsushita M, Ishiguro N

    Intractable & rare diseases research   Vol. 3 ( 2 ) page: 46-51   2014.5

     More details

    Language:English  

    DOI: 10.5582/irdr.2014.01009

    PubMed

  9. Benign prenatal hypophosphatasia: a treatable disease not to be missed. Reviewed

    Matsushita M, Kitoh H, Michigami T, Tachikawa K, Ishiguro N

    Pediatric radiology   Vol. 44 ( 3 ) page: 340-3   2014.3

     More details

    Language:English  

    DOI: 10.1007/s00247-013-2805-z

    PubMed

  10. A novel in-frame deletion of the RUNX2 gene causes a classic form of cleidocranial dysplasia. Reviewed

    Matsushita M, Kitoh H, Kaneko H, Mishima K, Itoh Y, Tokita Y, Ishiguro N

    Journal of bone and mineral metabolism   Vol. 32 ( 1 ) page: 96-9   2014.1

     More details

    Language:English  

    DOI: 10.1007/s00774-013-0456-7

    PubMed

  11. A comparative study of blade plate fixation and external fixation in osteotomies for slipped capital femoral epiphysis. Reviewed

    Kitoh H, Kitakoji T, Hattori T, Kaneko H, Mishima K, Matsushita M, Ishiguro N

    Journal of pediatric orthopedics. Part B   Vol. 22 ( 6 ) page: 542-7   2013.11

     More details

    Language:English  

    DOI: 10.1097/BPB.0b013e3283637070

    PubMed

  12. Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial. Reviewed

    Kitoh H, Achiwa M, Kaneko H, Mishima K, Matsushita M, Kadono I, Horowitz JD, Sallustio BC, Ohno K, Ishiguro N

    Orphanet journal of rare diseases   Vol. 8   page: 163   2013.10

     More details

    Language:English  

    DOI: 10.1186/1750-1172-8-163

    PubMed

  13. A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild campomelic dysplasia and small patella syndrome. Reviewed

    Matsushita M, Kitoh H, Kaneko H, Mishima K, Kadono I, Ishiguro N, Nishimura G

    American journal of medical genetics. Part A   Vol. 161A ( 10 ) page: 2528-34   2013.10

     More details

    Language:English  

    DOI: 10.1002/ajmg.a.36134

    PubMed

  14. Long-term outcome of gradual reduction using overhead traction for developmental dysplasia of the hip over 6 months of age. Reviewed

    Kaneko H, Kitoh H, Mishima K, Matsushita M, Ishiguro N

    Journal of pediatric orthopedics   Vol. 33 ( 6 ) page: 628-34   2013.9

     More details

    Language:English  

    DOI: 10.1097/BPO.0b013e31829b2d8b

    PubMed

  15. Prognostic factors for trochanteric overgrowth after containment treatment in Legg-Calvé-Perthes disease. Reviewed

      Vol. 22 ( 5 ) page: 432-6   2013.9

     More details

    Language:English  

    DOI: 10.1097/BPB.0b013e32835f585b

    PubMed

  16. Orthopaedic manifestations and diagnostic clues in children with Guillain-Barré syndrome. Reviewed

      Vol. 7 ( 3 ) page: 177-82   2013.6

     More details

    Language:English  

    DOI: 10.1007/s11832-012-0475-2

    PubMed

  17. Clinically applicable antianginal agents suppress osteoblastic transformation of myogenic cells and heterotopic ossifications in mice. Reviewed

    Yamamoto R, Matsushita M, Kitoh H, Masuda A, Ito M, Katagiri T, Kawai T, Ishiguro N, Ohno K

    Journal of bone and mineral metabolism   Vol. 31 ( 1 ) page: 26-33   2013.1

     More details

    Language:English  

    DOI: 10.1007/s00774-012-0380-2

    PubMed

  18. Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia. Reviewed

    Matsushita M, Kitoh H, Ohkawara B, Mishima K, Kaneko H, Ito M, Masuda A, Ishiguro N, Ohno K

    PloS one   Vol. 8 ( 12 ) page: e81569   2013

     More details

    Language:English  

    DOI: 10.1371/journal.pone.0081569

    PubMed

  19. Isolated bifid rib: clinical and radiological findings in children. Reviewed

    Kaneko H, Kitoh H, Mabuchi A, Mishima K, Matsushita M, Ishiguro N

    Pediatrics international : official journal of the Japan Pediatric Society   Vol. 54 ( 6 ) page: 820-3   2012.12

     More details

    Language:English  

    DOI: 10.1111/j.1442-200X.2012.03672.x

    PubMed

▼display all

Presentations 29

  1. 7. Abnormal growth plate structure in mouse model of hypophosphatemic rickets is ameliorated by meclozine treatment International conference

    Yasunari Kamiya, Masaki Matsushita, Kenichi Mishima, Bisei Ohkawara, Shiro Imagma, Kinji Ohno, Hiroshi Kitoh

    Orthopaedic Research Society 2022 Annual Meeting 

     More details

    Event date: 2022.2

    Language:English   Presentation type:Poster presentation  

  2. Health-related quality of life in patients with multiple epiphyseal dysplasia and spondyloepiphyseal dysplasia International conference

    Masaki Matsushita, Kenichi Mishima, Yasunari Kamiya, Nobuhiko Haga, Sayaka Fujiwara, Keiichi Ozono, Takuo Kubota, Taichi Kitaoka, Shiro Imagama, Hiroshi Kitoh

    13th Combined Meeting of Asia Pacific Spine Society & Asia Pacific Paediatric Orthopaedic Society (APSS-APPOS 2021) 

     More details

    Event date: 2021.6

    Language:English   Presentation type:Oral presentation (general)  

  3. Efficacy and tolerability of meclozine for the treatment of short stature in a mouse model of achondroplasia International conference

    Masaki Matsushita, Kenichi Mishima, Tadashi Nagata, Yasunari Kamiya, Shiro Imagama, Kinji Ohno, Hiroshi Kitoh

    2021 Annual Meeting - Orthopaedic Research Society (ORS) 

     More details

    Event date: 2021.2

    Language:English   Presentation type:Poster presentation  

  4. Periosteal resection promotes longitudinal bone growth via activating endochondral ossification in growing mouse model International conference

    Shinya Kaneko, Masaki Matsushita, Kenichi Mishima, Hiroshi Kitoh, Naoki Ishiguro

    2020 Annual Meeting - Orthopaedic Research Society (ORS) 

     More details

    Event date: 2020.2

    Language:English   Presentation type:Poster presentation  

  5. Efficacy of soluble lansoprazole-impregnated artificial bones for repairing cortical bone defects in rabbits International conference

    Kenichi Mishima, Ryusaku Esaki, Masaki Matsushita, Naoki Ishiguro

    2020 Annual Meeting - Orthopaedic Research Society (ORS) 

     More details

    Event date: 2020.2

    Language:English   Presentation type:Poster presentation  

  6. Local administration of meclozine promotes the longitudinal growth of selected bone in mouse model International conference

    Tadashi Nagata, Masaki Matsushita, Kenichi Mishima, Yasunari Kamiya, Bisei Ohkawara, Kinji Ohno, Naoki Ishiguro, Hiroshi Kitoh

    2020 Annual Meeting - Orthopaedic Research Society (ORS) 

     More details

    Event date: 2020.2

    Language:English   Presentation type:Poster presentation  

  7. Meclozine promotes bone growth and bone mineralization in mouse model of hypophosphatemic rickets International conference

    Yasunari Kamiya, Masaki Matsushita, Kenichi Mishima, Tadashi Nagata, Naoki Ishiguro, Kinji Ono, Hiroshi Kitoh

    2020 Annual Meeting - Orthopaedic Research Society (ORS) 

     More details

    Event date: 2020.2

    Language:English   Presentation type:Poster presentation  

  8. Drug repositioning for FGF23-mediated hypophosphatemia: Disulfiram lowers FGF23 production International conference

    Kenichi Mishima, Hiroshi Sugiura, Ryusaku Esaki, Masaki Matsushita, Hiroshi Kitoh, Naoki Ishiguro, Kinji Ohno

    2019 Annual Meeting - Orthopaedic Research Society (ORS) 

     More details

    Event date: 2019.2

    Language:English   Presentation type:Poster presentation  

  9. Long term health-related quality of life in patients with achondroplasia and hypochondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Naoki Ishiguro, Sayaka Fujiwara, Nobuhiko Haga, Taichi Kitaoka, Takuo Kubota, Keiichi Ozono

    American Society for Bone and Mineral Research (ASBMR) 2018 Annual Meeting 

     More details

    Event date: 2018.9 - 2018.10

    Language:English   Presentation type:Poster presentation  

  10. 小児先天性疾患に合併した下腿変形に対するMAC創外固定器による矯正

    松下雅樹、鬼頭浩史、三島健一、長田侃、金子浩史、岩田浩志、服部義、石黒直樹

    第31回日本創外固定・骨延長学会  2018.8.4 

     More details

    Event date: 2018.8

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  11. Bone formation was promoted in mouse model of distraction osteogenesis with gain-of-function mutation in FGFR3 International conference

    Masaki Matsushita, Yusuke Ohsawa, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno, Hiroshi Kitoh

    Fibroblast Growth Factors in Development & Disease - Gordon Research Conference 2018 

     More details

    Event date: 2018.3

    Language:English   Presentation type:Poster presentation  

  12. Treatment of the lower limb deformities by a multi-axial external fixation system Invited International conference

    Masaki Matsushita, Hiroshi Kitoh, Tadashi Hattori, Hiroshi Kaneko, Kenichi Mishima, Naoki Ishiguro

    The 61st Korean Orthopaedic Association Annual Meeting 

     More details

    Event date: 2017.10

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  13. Clinically Feasible Dose of Meclozine Improves Bone Growth, Bone Volume, and Bone Quality in Mouse Model with Achondroplasia International conference

    Masaki Matsushita, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno, Hiroshi Kitoh

    The 27th Korean-Japanese Combined Orthopaedic Symposium (KJCOS) 2017 

     More details

    Event date: 2017.5

    Language:English   Presentation type:Oral presentation (general)  

  14. Clinically feasible dose of meclozine promotes bone growth in mouse model with achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Hiroshi Sugiura, Sachi Hasegawa, Akiko Kitamura, Naoki Ishiguro, Kinji Ohno

    2017 Annual Meeting - Orthopaedic Research Society (ORS) 

     More details

    Event date: 2017.5

    Language:English   Presentation type:Poster presentation  

  15. Long term health-related quality of life in achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Satoshi Yamashita, Hiroshi Sugiura, Akiko Kitamura, Naoki Ishiguro

    Combined European Paediatric Orthopaedic Society and Pediatric Orthopaedic Society of North America (EPOSNA) 2017 Annual meeting 

     More details

    Event date: 2017.5

    Language:English   Presentation type:Poster presentation  

  16. Clinical feasibility of meclozine for improvement of short stature in achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Hiroshi Sugiura, Akiko Kitamura, Naoki Ishiguro

    Combined European Paediatric Orthopaedic Society and Pediatric Orthopaedic Society of North America (EPOSNA) 2017 Annual meeting 

     More details

    Event date: 2017.5

    Language:English   Presentation type:Poster presentation  

  17. 軟骨無形成症に対する根本的治療の開発

    松下雅樹、鬼頭浩史、 三島健一、杉浦洋、長谷川幸、北村暁子、石黒直樹、大野欽司

    第27回日本小児整形外科学会  2016.12.1 

     More details

    Event date: 2016.12

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  18. Clinical feasibility of oral administration of meclozine for the treatment of short stature in achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno

    American Society for Bone and Mineral Research (ASBMR) 2016 Annual Meeting 

     More details

    Event date: 2016.9

    Language:English   Presentation type:Poster presentation  

  19. Clinically attainable concentration of meclozine has a potent effect on promoting bone growth in achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno

    Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016 

     More details

    Event date: 2016.8

    Language:English   Presentation type:Poster presentation  

  20. Clinically attainable concentration of meclozine promotes bone growth in transgenic mice with achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno

    Fibroblast Growth Factors in Development & Disease - Gordon Research Conference 2016 

     More details

    Event date: 2016.6

    Language:English   Presentation type:Poster presentation  

  21. Radical therapeutic strategy for foramen magnum stenosis and spinal canal stenosis in achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Hiroshi Sugiura, Sachi Hasegawa, Akiko Kitamura, Naoki Ishiguro, Kinji Ohno

    2016 Annual Meeting - Orthopaedic Research Society (ORS) 

     More details

    Event date: 2016.3

    Language:English   Presentation type:Oral presentation (general)  

  22. 軟骨無形成症治療の現在と未来 Invited

    松下雅樹

    Nordiscience Ach workshop  2015.11.21 

     More details

    Event date: 2015.11

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  23. Meclozine has a potential effects on short stature and foramen magnum stenosis in transgenic mice with achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Hiroshi Sugiura, Sachi Hasegawa, Akiko Kitamura, Ishiguro Naoki, Ohno Kinji

    7th International Conference on Children’s Bone Health (ICCBH) 2015 

     More details

    Event date: 2015.6

    Language:English   Presentation type:Oral presentation (general)  

  24. Meclozine promotes longitudinal bone growth in transgenic achondroplasia mice with gain-of-function mutation in FGFR3 gene International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Naoki Ishiguro

    2015 Pediatric Orthopaedic Society of North America (POSNA) Annual Meeting 

     More details

    Event date: 2015.4 - 2015.5

    Language:English   Presentation type:Oral presentation (general)  

  25. Meclozine enhances skeletal growth in transgenic achondroplasia mice with a constitutive active FGFR3 mutation International conference

    Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno

    2015 Annual Meeting - Orthopaedic Research Society (ORS) 

     More details

    Event date: 2015.3

    Language:English   Presentation type:Poster presentation  

  26. Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Hiroshi Kaneko, Kenichi Mishima, Naoki Ishiguro

    2014 Pediatric Orthopaedic Society of North America (POSNA) Annual Meeting 

     More details

    Event date: 2014.4 - 2014.5

    Language:English   Presentation type:Poster presentation  

  27. Meclozine facilitates chondrocyte proliferation and differentiation by attenuating abnormally activated FGFR3 signaling in achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Hiroshi Kaneko, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno

    International Skeletal Dysplasia Society (ISDS) Meeting 2013 

     More details

    Event date: 2013.8

    Language:English   Presentation type:Oral presentation (general)  

  28. Drug repositioning for inhibiting the FGFR3 signaling in the treatment of short stature in achondroplasia International conference

    Masaki Matsushita, Hiroshi Kitoh, Naoki Ishiguro, Kinji Ohno

    2013 Annual Meeting - Orthopaedic Research Society (ORS) 

     More details

    Event date: 2013.1

    Language:English   Presentation type:Poster presentation  

  29. Guillain-Barré syndrome of children -diffficulty to diagnosis in the orthopedic field- International conference

    Masaki Matsushita, Tadashi Hattori, Takahiko Kitakoji, Hiroshi Iwata

    Asia Pacific Orthopaedic Association (APOA), Spine and Pediatric Sections 2011 

     More details

    Event date: 2011.6

    Language:English   Presentation type:Oral presentation (general)  

▼display all

KAKENHI (Grants-in-Aid for Scientific Research) 11

  1. FGFR3インヒビターのマウスモデルへの長期投与と作用機序の検討

    Grant number:22K09398  2022.4 - 2025.3

    科学研究費助成事業  基盤研究(C)

    松下 雅樹

      More details

    Authorship:Principal investigator 

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

  2. 多階層シングルセル解析を応用した骨再生機構の解明と新規再生療法の基盤構築

    Grant number:21H03124  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(B)

    松下 祐樹, 尾崎 遼, 住田 吉慶, 松下 雅樹

      More details

    Authorship:Coinvestigator(s) 

  3. Development of therapeutic drugs fro achondroplasia-Examination of FGFR3 inhibitory effects of meclizine hydrochloride

    Grant number:21H03063  2021.4 - 2024.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

      More details

    Authorship:Coinvestigator(s) 

  4. 骨延長マウスモデルにおけるメクロジンのFGFR3抑制効果の検討

    Grant number:20K09477  2020.4 - 2023.3

    科学研究費助成事業  基盤研究(C)

    神谷 庸成, 鬼頭 浩史, 三島 健一, 松下 雅樹, 長田 侃

      More details

    Authorship:Coinvestigator(s) 

    軟骨無形成はFGFR3が異常に活性化し骨伸長が抑制される難病である。申請者のグループは、drug repositioningによりメクロジンがFGFR3インヒビターであることを見出し、Achマウスの骨伸長を促進したことを報告した。また、メクロジンはHypマウスの表現型をレスキューしたことを見出した。一方、Achマウスは骨延長における骨形成が亢進していることを報告した。本研究では、骨延長マウスモデルにメクロジンを投与し骨形成におけるメクロジンの効果を検討する。骨延長はAchマウスとhypマウスに行い、骨延長部を経時的にレントゲンおよび組織学的に定量しメクロジンの効果を非投与群と比較する。
    申請者のグループはドラッグスクリーニングの手法を用いて、乗り物酔い止め薬であるメクロジンが軟骨無形成症で異常活性化しているFGFR3シグナルを抑制することを過去に見出し、その効果により低リン血症性くる病マウスモデルの表現型も改善したことを見出した。一方で、これらの疾患は低身長や下肢変形に対する治療として骨延長術を行われることがある。骨延長部の骨形成について、軟骨無形成症モデルマウスでは良好であることはすでに申請者のグループから報告したが、低リン血症性くる病ではマウスモデルで検討された報告はない。さらにそれら疾患モデルマウスの骨延長モデルに対するメクロジンの効果についても研究はされていない。これらを背景として本研究では、軟骨無形成症マウスモデル、低リン血症性くる病マウスモデル、および対照として野生型マウスの骨延長モデルを作成し、それぞれを比較するとともに、メクロジンの経口投与群と非投与群とを比較検討する。2020年度において、離乳後の野生型マウスと低リン血症性くる病マウスモデルに対して骨延長モデルを作成し、経時的な画像評価と組織標本の評価を行ったが、低リン血症性くる病マウスモデルでは延長部の骨形成が不良であった。低リン血症性くる病マウスモデルは下肢骨が極めて短く折れやすいため、延長モデルを作成した過去の報告はなく、この作成が可能であったことにより他の薬剤による効果を検証する実験系の確立が出来た。
    経口投与群と非経口投与群の骨延長モデルの作製は順調に進んでおり、経時的なCT撮像、組織標本作製も進められている。しかしながら研究分担者であった長田の退職による人的資源不足を起因として、結果評価について当初の予定よりやや遅れている。
    マイクロCTおよび組織標本の評価を進め、メクロジン投与の最適化を行うとともに、軟骨無形成症マウスモデルにおいても同様にモデル作成、メクロジン投与、マイクロCTおよび組織標本評価を行っていく。

  5. ドラッグリポジショニングによるペルテス病の新規治療法の開発

    Grant number:19K09573  2019.4 - 2022.3

    科学研究費助成事業  基盤研究(C)

    三島 健一, 鬼頭 浩史, 松下 雅樹, 長田 侃, 神谷 庸成

      More details

    Authorship:Coinvestigator(s) 

    ペルテス病の病態制御には、修復過程における①血管新生の遅延、②活発な壊死骨の吸収、③骨新生の抑制のそれぞれが治療ターゲットとなり得る。申請者らは既存薬であるランソプラゾールに骨形成促進作用が存在することを見出しており、骨吸収抑制薬にはすでにビスフォスフォネート製剤が使われている。骨壊死に続発する股関節炎の遷延は、血管新生の遅延や骨新生の抑制に関与するが、慢性炎症の薬物治療は関節リウマチや敗血症性ショックの基礎研究から開発が進んでいる。本研究の目的は骨壊死によって生じる3つの病態をドラッグリポジショニング薬剤と既存薬との併用療法によって改善することで、ペルテス病の自然歴の改変を試みることである。
    今年度は成人の特発性大腿骨頭壊死症あるいは小児のペルテス病を想定した虚血性骨壊死症に対する水溶性ランソプラゾール(タケプロン点滴用)単独の効果を調べる動物実験を行った。実験はマウスの大腿骨遠位顆部を栄養する主要な血管4本を顕微鏡にて同定し、これらをすべて凝固焼灼して虚血性骨壊死を誘導する動物モデルを使用して行った。馴化した6週齢の雄C57BL/6マウスの左後肢に上記の手術操作を施し、骨壊死部に新生血管の再分布が開始される施術3週後から1日1回水溶性ランソプラゾールの尾静脈内投与を行った。水溶液の濃度は細胞実験での結果を踏まえ、ヒト成人において実臨床で使用される濃度の約10~20倍とし、4 mg/kg/dayと8 mg/kg/dayを設定した。尾静脈投与における保定操作は愛護的に行い、暴れることによって過剰な負荷が加わり壊死骨端が圧潰しないように留意した。尾静脈投与は毎回薬液の漏れなく実施することができ、穿刺部の感染を起こすことはなかった。実験中に削痩や脱毛を生じることはなかった。施術後6週で安楽死させ、左後肢から大腿骨と脛骨を膝関節は残したまま採取した。肉眼的な評価では4 mg/kg/dayあるいは8 mg/kg/dayでの薬剤投与群の方が対照群と比べて大腿骨遠位顆部骨端の著しい破壊損傷は少ないように見えた。μ-CT検査による画像解析の予定であったが、撮影装置に重大な故障が生じてしまったため中止を余儀なくされている。今後μ-CT検査による骨端の圧潰状況や骨梁海綿骨の三次元微細構造評価を予定している。
    今年度は年度当初から新型コロナウイルス感染症の世界的なパンデミックのため、当地においても実験施設の閉鎖や利用制限、実験資材や実験動物の供給停止や遅延、実験手技をサポートしてくれるテクニシャンや大学院生の入構禁止や制限、感染流行地との往来禁止や制限が続き、研究の進捗に著しく影響した。感染の流行が落ち着き、実験が再開されてからは、画像撮影装置の重大な故障が生じたため、動物実験の画像解析が停止してしまい、研究の進捗状況に大幅に遅れを生じることとなった。
    来期からもマウス大腿骨虚血性骨壊死モデルを使用して水溶性ランソプラゾールの全身投与による壊死骨の圧壊抑制効果を検証していく。先期での動物実験において濃度依存性の薬効が認められた場合にはさらに高用量あるいは1日複数回での投与を予定する。次に骨壊死の病態の時間的進行に即してタイムリーに他の薬剤を使用することでさらに壊死骨の圧潰抑制を実現できるかどうか検討するため、骨壊死誘導後3週までの早期に骨吸収抑制薬あるいは免疫調節療法薬の全身投与を行い、3週後から水溶性ランソプラゾールに切り換え、同様に薬効を評価する予定にしている。

  6. 新規軟骨無形成症治療薬開発研究

    Grant number:19K09646  2019.4 - 2022.3

    科学研究費助成事業  基盤研究(C)

    松下 雅樹, 鬼頭 浩史, 三島 健一, 長田 侃, 神谷 庸成

      More details

    Authorship:Principal investigator 

    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    メクロジンは軟骨細胞においてFGFR3シグナルを抑制し、ACHマウスモデルへの経口投与により骨伸長促進効果が認められている。本研究では、メクロジンによるACHの根本的治療開発に向けて、FGFR3シグナルにおけるメクロジンの作用機序を検討する。FGFR3シグナルのMAPK経路のうちERKの上流に位置するMEKやRAF、さらにSTAT経路に与える効果や生体内にユビキタスに発現しているERKのリン酸化に与える影響を検討する。また、ACHマウスモデルに各種濃度のメクロジンを投与して副作用が少なく最大限効果を発揮できる用量やACH以外のFGFR3シグナルが関連した疾患動物モデルにおける効果を検討する。
    乗り物酔い防止薬の成分であるメクロジンは軟骨細胞において線維芽細胞増殖因子受容体3(fibroblast growth factor receptor 3 : FGFR3) シグナルを抑制し、軟骨無形成症(achondroplasia:ACH)マウスモデルへの経口投与により骨伸長促進効果が認められている。これまでの研究で、7日齢のACHマウスモデル(Achマウス)に10日間メクロジンを投与したところ、1および2 mg/kg/dayで濃度依存性に骨伸長を促進したが、20 mg/kg/dayでは有効性が認められなかった。令和1年度は、4および8 mg/kg/dayをAchマウスに同様のプロトコールで投与し骨長を評価したところ、本プロトコールにおいてはメクロジン2 mg/kg/dayが、副作用が少なく最大限骨伸長効果を発揮できる用量と考えた。令和2年度は、メクロジン2 mg/kg/dayの有効性を検証するためにHypマウスの骨幹端部の骨梁および骨幹部の骨皮質のosteoid volume/bone volume (OV/BV) を定量した。メクロジン2 mg/kg/dayはHypマウスのOV/BVを有意に減少させた。また、メクロジンはHypマウスの成長軟骨の構造を改善した。さらに、メクロジンはHypマウスの血清カルシウムおよびリン値を有意に上昇させた。
    メクロジンの作用機序の検討について、令和1年度にcell freeキナーゼアッセイを行ったところ、メクロジンはMAPKカスケードにおけるMAP3K3のリン酸化を抑制することが示唆された。令和2年度には、胎生16.5日齢の脛骨にFGF2とメクロジンを添加した器官培養軟骨のRNA-seqを行った。FGF2を添加するとMAPKファミリーカスケードに属する遺伝子は有意に変動したが、メクロジンはこれを打ち消した。
    令和2年度は、Achマウスにおいて最も有効だった2mg/kg/dayのメクロジンを7日齢のHypマウスに投与し、骨幹端部の骨梁および骨幹部の骨皮質の組織標本をVillanueva Goldner染色しosteoid volume/bone volume (OV/BV) を定量した。また、血清カルシウム、リン、FGF23を計測した。メクロジン2 mg/kg/dayをHypマウスに投与するとHypマウスで増加しているOV/BVは有意に減少した。また、Hypマウスの成長軟骨では肥大軟骨細胞層は肥厚しているがメクロジンの投与により肥大軟骨細胞層の厚みは有意に減少した。さらに、メクロジンはHypマウスの血清カルシウムおよびリン値を有意に上昇させたが、Hypマウスで上昇しているFGF23はさらに上昇した。一方、マイクロCTによる各種海綿骨や皮質骨のパラメータはメクロジン2 mg/kg/dayの投与により変化しなかった。
    令和1年度に行なったcell freeキナーゼアッセイによりメクロジンはMAPK経路においてMAP3K3のリン酸化を抑制することが示唆された。メクロジンのMAPK経路抑制効果を検証するために、胎生16.5日の脛骨器官培養系を用いた。FGF2とメクロジンを投与して培養を行った後に軟骨よりRNAを抽出し、GSEA解析を行った。FGF2によりMAPKファミリーカスケードに属する遺伝子発現は変動し、メクロジンはこの変動を打ち消した。
    令和2年度は、Achマウスにおいて有効性が認められた2 mg/kg/dayのメクロジンがHypマウスにおいても有効であることを示すことができた。また、脛骨器官培養軟骨においてメクロジンはMAPKファミリーカスケードに属する遺伝子を有意に変動させ、メクロジンがこれを抑制することを示した。以上により、本研究はおおむね順調に進んでいると考えている。
    これまでの研究よりメクロジンはMAPK経路においてMEK1/2のリン酸化を抑制することが予想されていた。しかし、令和1年度に施行したキナーゼアッセイでは、メクロジンはMEK1/2のリン酸化抑制効果は軽度だったのに対し、さらに上流のMAP3K3のリン酸化を抑制することが示唆された。令和2年度は、軟骨細胞においてFGFR3シグナルが亢進しMAPKファミリーカスケードに属する遺伝子の変動をメクロジンが抑制することを示した。令和3年度は、軟骨細胞における細胞内シグナルの検討を行うために、Rat chondrosarcoma(RCS)細胞にメクロジンを添加した後にFGF2を加えFGFR3シグナルが活性化した一定時間後にMAP3K3やMAP2K6のリン酸化抑制効果の評価に加え、ERK、p38、JNK経路における効果をウエスタンブロッティング法により評価する。
    Achマウスで最も効果を発揮するメクロジン2 mg/kg/dayは、Hypマウスにおいても有効であることを令和2年度までに示すことができた。令和3年には、サンプルサイズを増やしメクロジン2 mg/kg/dayの有効性を検証する。

  7. FGFR3インヒビターの局所投与による骨伸長促進効果の検討

    Grant number:19K09596  2019.4 - 2021.3

    科学研究費助成事業  基盤研究(C)

    長田 侃, 鬼頭 浩史, 三島 健一, 松下 雅樹, 神谷 庸成

      More details

    Authorship:Coinvestigator(s) 

    軟骨無形成症(achondroplasia: ACH)は骨伸長の抑制因子であるFGFR3の活性化により発症し、長管骨の長軸成長が障害され低身長を呈する骨系統疾患である。研究代表者らは、メクロジンが新規FGFR3インヒビターであると同定し、ACHマウスモデルへの全身投与により骨伸長を促進したことを報告した。本研究ではFGFR3インヒビターの局所投与による骨伸長促進効果を検討する。幼弱動物の片側関節内や骨端部にFGFR3インヒビターを局所投与し、マイクロCTで骨長を経時的に測定して非投与側と比較する。成長軟骨板の組織学的検討、骨端および骨幹端の骨量や骨梁に対する骨形態学的検討も加える。
    特定の短縮した骨に対する治療法は、侵襲の大きい骨延長術しかない。本研究の目的は、マウスモデルへの全身投与により骨伸長促進効果が認められている線維芽細胞増殖因子受容体3(fibroblast growth factor receptor 3 : FGFR3)インヒビターの局所投与による骨伸長促進効果を検討することである。これまでに、4週齢の野生型マウスの膝関節に100μMのメクロジン30μLを計6回隔日投与し非投与側と比較検討したところ脛骨において有意な骨伸長効果を認めた。令和1年度には、軟骨無形成症(achondroplasia:ACH)マウスモデル(ACHマウス)を用いて同様に局所投与し、ACHマウスにおいても脛骨の有意な骨伸長効果を認めた。また、メクロジン最終投与後に蛍光カルシウムキレート剤2種を24時間差で腹腔内投与し24時間あたりの骨伸長量を定量すると、野生型マウスおよびACHマウスで、大腿骨と脛骨における骨伸長効果を認めた。最終年度である令和2年度は、メクロジンの至適局所投与量の検討を行った。100μMのメクロジン10μLを同様のプロトコールで野生型マウスに投与した。骨伸長および骨量は増加傾向であったものの30μL投与時よりは効果は小さいことから、100μMメクロジン10μLよりも30μLが有効と考えた。また、薬剤の膝関節局所投与による成長軟骨への移行を評価した。Indian inkを膝関節に投与し成長軟骨を組織学的に評価すると成長軟骨にIndian inkの染色性が認められた。
    今後は、膝関節局所投与による骨伸長効果を示すデータを蓄積するために、成長軟骨の組織学的評価を追加する。また、メクロジン以外のFGFR3インヒビターによる局所投与の骨伸長効果も検討する。局所投与による選択的に骨伸長を促進する治療法が確立されれば非侵襲的な治療法の開発へ結びつく可能性がある。

  8. Investigation of osteochondral function via activation of FGFR3 signaling

    Grant number:17H04312  2017.4 - 2020.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Kitoh Hiroshi

      More details

    Authorship:Coinvestigator(s) 

    We demonstrated that new bone formation was accelerated during limb lengthening surgery and cartilage degeneration was inhibited via suppressing subchondral bone sclerosis in transgenic mice expressing activated fGFR3 signaling. We concluded that FGFR3 has a positive effect of bone regeneration and joint cartilage preservation. On the other hand, although it is known that FGFR3 signaling suppresses longitudinal bone growth, meclizine, which we found as a drug of FGFR3 inhibitor, significantly promoted bone growth in mice carrying a FGFR3 activating mutation. We determined that the optimal dose of meclizine on bone growth was 2mg/kg/day, and the minimal hepatotoxicity dose of meclizine was 8 mg/kg/day.

  9. Drug repositioning for successful healing of bone fractures or defects

    Grant number:16K10854  2016.4 - 2020.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MISHIMA KENICHI

      More details

    Authorship:Coinvestigator(s) 

    We previously reported that lansoprazole accelerated the physiological process of fracture healing in rats. At first, we sought to determine if insoluble lansoprazole could promote local bone formation when combined with beta-TCP bone substitutes in a rabbit cortical bone defect model. However, we failed to demonstrate their therapeutic efficacy because the materials were surrounded with dense granulomatous tissues. Next, we have developed soluble lansoprazole-impregnated artificial bones and evaluated their efficacy by applying to the model.In contrast to the previous experiments using insoluble lansoprazole, significant efficacy of soluble lansoprazole-impregnated bone graft substitutes on local bone accrual could be identified. These results indicate that brief exposure of resident and circulating osteoblastic lineage cells to lansoprazole can be sufficient to enhance local bone regeneration in vivo without apparent cytotoxicity.

  10. Development of therapeutic drugs for fibrodysplasia ossificans progressiva by drug repositioning strategies

    Grant number:15K15548  2015.4 - 2018.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    Kitoh Hiroshi

      More details

    Authorship:Coinvestigator(s) 

    Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by progressive heterotopic ossification in various extraskeletal sites. FOP is caused by a gain-of-function mutation in ALK2, which causes up regulation of a transcriptional factor, Id1. We screened FDA-approval drugs for suppression of the Id1 promoter activated by the mutant ALK2 in C2C12 myogenic cells. We found that azelastine HCl (anti-histamine), Fluvastatin sodium salt (ant-hyperlipidemia), and Trimipramine maleate salt (anti-depressant) suppressed the Id1 promoter activity in a dose-dependent manner. These drugs also downregulated the expressions of the Id1-target osteoblastic genes such as alkaline phosphatase and osteocalcin.

  11. Animal study for evaluating the effect of meclozine on FGFR3 signaling

    Grant number:15K10439  2015.4 - 2018.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Matsushita Masaki

      More details

    Authorship:Principal investigator 

    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    Achondroplasia (ACH) is characterized by short stature associated with severe complications such as stenoses of foramen magnum and spinal canal due to the gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR3). We have already found that meclozine, an anti-histamine drug that has long been used for motion sickness, inhibited FGFR3 signaling. In the current study, the 1 or 2 mg/kg/day of meclozine increased the bone length of 7-day-old Ach mice for 10 days, but did not rescue the foramen magnum stenosis. Meclozine administration would be commenced immediately after birth since the synchondroses around the foramen magnum was closed at the age of 4.5 days. On the other hand, the 1 or 2 mg/kg/day of meclozine increased the bone volume and bone mineral density in addition to the bone length in growing Ach mice.

▼display all