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Elucidation of molecular mechanism of the regulation of skeletal homeostasis, and development of new therapeutic approaches against skeletal disorders

Research Project

Project/Area Number 25293215
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Endocrinology
Research InstitutionThe University of Tokushima

Principal Investigator

MATSUMOTO Toshio  徳島大学, 藤井節郎記念医科学センター, 副理事 (20157374)

Co-Investigator(Kenkyū-buntansha) FUKUMOTO Seiji  徳島大学, 藤井節郎記念医科学センター, 特任教授 (30202287)
ABE Masahiro  徳島大学, 大学院医歯薬学研究部, 教授 (80263812)
遠藤 逸朗  徳島大学, 大学病院, 講師 (10432759)
粟飯原 賢一  徳島大学, ヘルスバイオサイエンス研究部, 講師 (70372711)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywordsインターロイキン-11 (IL-11) / Wntシグナル / 骨芽細胞 / 脂肪細胞 / 骨髄腫 / 破骨細胞 / Pim-2 / 遺伝子 / シグナル伝達 / 脂質 / 老化
Outline of Final Research Achievements

IL-11 regulates osteoblast/adipocyte differentiation via Wnt signaling. In order to clarify the role of IL-11 on the regulation of osteogenesis and adipogenesis, we created IL-11 knockout mice. These mice exhibited reduced bone mass due to suppressed bone formation, along with increased adipose tissue mass with insulin resistance and glucose intolerance. These results demonstrate the important role of IL-11 in the regulation of osteoblast/adipocyte differentiation.
Interaction of myeloma cells with bone cells enhanced Pim-2 expression in myeloma cells, and Pim-2 enhanced survival and drug resistance of myeloma cells. Myeloma cell-osteoblast interaction also enhanced Pim-2 expression in osteoblasts, which suppressed osteoblast differentiation. Furthermore, Pim inhibitors potently suppressed myeloma growth and enhanced bone formation. These observations suggest that inhibition of Pim-2 may become a new therapeutic approach against multiple myeloma.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (28 results)

All 2015 2014 2013 Other

All Journal Article (19 results) (of which Peer Reviewed: 19 results,  Open Access: 8 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma.2015

    • Author(s)
      Hiasa M, Teramachi J, Oda A, Amachi R, Harada T, Nakamura S, Miki H, Fujii S, Kagawa K, Watanabe K, Endo I, Kuroda Y, Yoneda T, Tsuji D, Nakao M, Tanaka E, Hamada K, Sano S, Itoh K, Matsumoto T, Abe M.
    • Journal Title

      Leukemia

      Volume: 29 Pages: 207-217

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effective impairment of myeloma cells and their progenitors by blockade of monocarboxylate transportation.2015

    • Author(s)
      Hanson DJ, Nakamura S, Amachi R, Hiasa M, Oda A, Tsuji D, Itoh K, Harada T, Horikawa K, Teramachi J, Miki H, Matsumoto T, Abe M.
    • Journal Title

      Oncotarget

      Volume: 6 Pages: 33568-33586

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH).2015

    • Author(s)
      Dong B, Endo I, Ohnishi Y, Kondo T, Hasegawa T, Amizuka N, Kiyonari H, Shioi G, Abe M, Fukumoto S, Matsumoto T.
    • Journal Title

      J Bone Miner Res

      Volume: 30 Pages: 1980-1993

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Effect of Discontinuing Treatment With Blosozumab: Follow-up Results of a Phase 2 Randomized Clinical Trial in Postmenopausal Women With Low Bone Mineral Density.2015

    • Author(s)
      ecknor CP, Recker RR, Benson CT, Robins DA, Chiang AY, Alam J, Hu L, Matsumoto T, Sowa H, Sloan JH, Konrad RJ, Mitlak BH, Sipos AA.
    • Journal Title

      J Bone Miner Res

      Volume: 30 Pages: 1717-1725

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density.2015

    • Author(s)
      Recker RR, Benson CT, Matsumoto T, Bolognese MA, Robins DA, Alam J, Chiang AY, Hu L, Krege JH, Sowa H, Mitlak BH, Myers SL.
    • Journal Title

      J Bone Miner Res

      Volume: 30 Pages: 216-224

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Eldecalcitol reduces osteoporotic fractures by unique mechanisms.2015

    • Author(s)
      Kondo S, Takano T, Ono Y, Saito H, Matsumoto T
    • Journal Title

      J Steroid Biochem Mol Biol

      Volume: 148 Pages: 232-238

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Effect of Discontinuing Treatment with Blosozumab: Follow-up Results of a Phase 2 Randomized Clinical Trial in Postmenopausal Women with Low Bone Mineral Density.2015

    • Author(s)
      Recknor CP, Recker RR, Benson CT, Robins DA, Chiang AY, Alam J, Hu L, Matsumoto T, Sowa H, Sloan JH, Konrad RJ, Mitlak BH, Sipos AA
    • Journal Title

      J Bone Miner Res

      Volume: E-pub Feb 24

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Defining and targeting myeloma stem cell-like cells.2014

    • Author(s)
      Abe M, Harada T, Matsumoto T
    • Journal Title

      Stem Cells

      Volume: 32 Pages: 1067-1073

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Magnetically responsive smart nanoparticles for cancer treatment with a combination of magnetic hyperthermia and remote-control drug release.2014

    • Author(s)
      Hayashi K, Nakamura M, Miki H, Ozaki S, Abe M, Matsumoto T, Sakamoto W, Yogo T, Ishimura K
    • Journal Title

      Theranostics

      Volume: 4 Pages: 834-844

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vitamin D analogs and bone: preclinical and clinical studies with eldecalctol.2014

    • Author(s)
      Matsumoto-T, Takano T, Saito H, Takahashi F
    • Journal Title

      BoneKEy Reports

      Volume: 3 Pages: 513-513

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fracture Risk Reduction with Denosumab in Japanese Postmenopausal Women and Men with Osteoporosis: Denosumab fracture Intervention RandomizEd placebo Controlled Trial (DIRECT).2014

    • Author(s)
      Nakamura T, Matsumoto T, Sugimoto T, Hosoi T, Miki T, Gorai I, Yoshikawa H, Tanaka Y, Tanaka S, Sone T, Nakano T, Ito M, Matsui S, Yoneda T, Takami H, Watanabe K, Osakabe T, Shiraki M, Fukunaga M
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 99 Pages: 2599-2607

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship Between The Effect Of Eldecalcitol And Serum 25(OH)D Level.2014

    • Author(s)
      Takano T, Kondo S, Saito H, Matsumoto T
    • Journal Title

      J Steroid Biochem Mol Biol

      Volume: 144 Pages: 124-127

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High serum parathyroid hormone and calcium are risk factors for hypertension in Japanese patients.2014

    • Author(s)
      Yagi S, Aihara K, Kondo T, Endo I, Hotchi J, Ise T, Iwase T, Akaike M, Matsumoto T, Sata M
    • Journal Title

      Endocr J

      Volume: 61 Pages: 727-733

    • NAID

      130004443979

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma.2014

    • Author(s)
      Hiasa M, Jumpei T, Oda A, Amachi R, Harada T, Nakamura S, Miki S, Fujii S, Kagawa K, Watanabe K, Endo I, Kuroda Y, Yoneda T, Tsuji D, Nakao M, Tanaka E, Hamada K, Sano S, Itoh K, Matsumoto T, Abe M.
    • Journal Title

      Leukemia

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Concise review: defining and targeting myeloma stem cell-like cells.2014

    • Author(s)
      Abe M, Harada T, Matsumoto T
    • Journal Title

      Stem cells (Dayton, Ohio)

      Volume: 32 Pages: 1067-1073

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Parathyroid hormone (1-34) counteracts the suppression of interleukin-11 expression by glucocorticoid in murine osteoblasts: a possible mechanism for stimulating osteoblast differentiation against glucocorticoid excess.2013

    • Author(s)
      Kuriwaka-Kido R, Kido S, Miyatani Y, Ito Y, Kondo T, Omatsu T, Dong B, Endo I, Miyamoto K, Matsumoto T
    • Journal Title

      Endocrinology

      Volume: 154 Pages: 1156-1167

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma.2013

    • Author(s)
      Harada T, Ozaki S, Oda A, Fujii S, Nakamura S, Miki H, Kagawa K, Takeuchi K, Matsumoto T, Abe M.
    • Journal Title

      Int J Hematol

      Volume: 97(6) Pages: 743-748

    • NAID

      10031183730

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activating transcription factor 4, an ER stress mediator, is required for, but excessive ER stress suppresses osteoblastogenesis by bortezomib.2013

    • Author(s)
      Nakamura S, Miki H, Kido S, Nakano A, Hiasa M, Oda A, Amou H, Watanabe K, Harada T, Fujii S, Takeuchi K, Kagawa K, Ozaki S, Matsumoto T, Abe M.
    • Journal Title

      Int J Hematol.

      Volume: 98 Pages: 66-73

    • NAID

      10031189598

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combination with a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide induces marked ADCC against myeloma cells and their progenitors.2013

    • Author(s)
      Harada T, Ozaki S, Oda A, Tsuji D, Ikegame A, Iwasa M, Udaka K, Fujii S, Nakamura S, Miki H, Kagawa K, Kuroda Y, Kawai S, Itoh K, Yamada-Okabe H, Matsumoto T, Abe M.
    • Journal Title

      PLoS One

      Volume: 8

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Pivotal role of TAK-1 in tumor growth and bone destruction in myeloma: therapeutic impact of TAK-1 inhibition.2015

    • Author(s)
      umpei Teramachi, Masahiro Hiasa, Asuka Oda, Hirofumi Tenshin, Ryota Amachi, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Tatsuji Haneji, Toshio Matsumoto and Masahiro Abe.
    • Organizer
      Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Seattle, WA. (USA)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RAIL is not a proapoptotic but rather anti-apoptotic mediator for osteoclasts to stimulate their differentiation and survival.2015

    • Author(s)
      Hirohfumi Tenshin, Jumpei Teramachi, Asuka Oda, Ryota Amachi, Masahiro Hiasa, Keiishiro Watanabe, Singen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto, Masahiro Abe.
    • Organizer
      Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Seattle, WA. (USA)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Spaceflight Bone Atrophy-Problem Solved?2015

    • Author(s)
      Adrian LeBlanc, Toshio Matsumoto, Jeffrey Jones, Jay Shapiro, Thomas Lang, Linda Shackelford, Scott M. Smith, Harlan Evans, Elisabeth Spector, Robert Ploutz-Snyder, Jean Sibonga, Joyce Keyak, Toshitaka Nakamura, Kenjiro Kohri, Hiroshi Ohshima, Gilbert Moralez.
    • Organizer
      Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Seattle, WA. (USA)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bisphosphonate ISS Flight Experiment.2014

    • Author(s)
      LeBlanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford L, Smith SM, Evans H, Spector E, Ploutz-Snyder R, Sibonga J, Keyak J, Nakamura T, Kohri K, Ohshima H, Moralez G
    • Organizer
      American Society of Bone and Mineral Research
    • Place of Presentation
      Houston (USA)
    • Year and Date
      2014-09-12 – 2014-09-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Interleukin-11 is an important factor for mechanical stress-induced osteoblast differentiation and bone formation.2014

    • Author(s)
      Takeshi Kondo, Bingzi Dong, Takashi Omatsu, Yukiyo Ohnishi, Itsuro Endo, Masahiro Abe, Shinichi Aizawa, Hiroshi Sakaue, Toshio Matsumoto
    • Organizer
      American Society of Bone and Mineral Research
    • Place of Presentation
      Houston (USA)
    • Year and Date
      2014-09-12 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Effect of a calcilytic compound in autosomal dominant hypocalcemia model mice.2014

    • Author(s)
      Bingzi Dong, Itsuro Endo, Takeshi Kondo, Yukiyo Ohnishi, Masahiro Abe, Seiji Fukumoto, Tomoka Hasegawa, Norio Amizuka, Shin-ichi Aizawa, Toshio Matsumoto
    • Organizer
      American Society of Bone and Mineral Research
    • Place of Presentation
      Houston (USA)
    • Year and Date
      2014-09-12 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Overview of the pathophysiology of MBD and acquired genetic events:Bench work for the targeted therapy to the microenvironment of MBD. Session: Myeloma bone disease.

    • Author(s)
      M Abe.
    • Organizer
      The 14th International Myeloma Workshop.
    • Place of Presentation
      Kyoto International Conference Center( Kyoto, Japan)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 骨髄腫骨病変と腫瘍免疫.シンポジウム5 骨免疫と炎症性疾患.

    • Author(s)
      安倍正博
    • Organizer
      第34回日本炎症・再生医学会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Potent induction of bone formation in myeloma bone lesions by the cathepsin K inhibitor KK1-300-01 in combination with the proteasome inhibitor bortezomib.

    • Author(s)
      Keiichiro Watanabe, Masahiro Abe, Hiroshi Mori, Ryota Amachi, Masahiro Hiasa, Takeshi Harada, Shiro Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto.
    • Organizer
      35th Annual Meeting, the American Society for Bone and Mineral Research, Baltimore
    • Place of Presentation
      Baltimore Convention Center(Baltimore, Maryland, USA)
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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