Molecular basis of regenerative therapy for musculoskeletal system using mechanical stress

• Project/Area Number: 15K20375
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Kagoshima University
• Principal Investigator: KUSUYAMA Joji 鹿児島大学, 医歯学総合研究科, 客員研究員 (70596105)
• Research Collaborator: MATSUGUCHI Tetsuya ; OHNISHI Tomokazu ; BANDOW Kenjiro ; SEMBA Ichiro ; SHIMA Kaori ; KAJIYA Yuka
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: メカニカルストレス / 間葉系幹細胞 / 骨芽細胞 / 脂肪細胞 / オステオポンチン / Syk / PLCgamma / 低出力超音波 / LIPUS / ＬＩＰＵＳ / 骨分化

Outline of Final Research Achievements

Mechanical stress is physical stimulation that applies to cells and tissues in our body. Musculoskeletal system system is one of the representative organ which are usually affected by mechanical stress. Previously, we showed that mechanical stress can regulate the multi-differentiation of mesenchymal stem cells. The goal of this study is to establish the molecular-based therapy to induce the maintenance and regeneration of musculoskeletal system by mechanical stress application. We found that physiological response to mechanical stress in osteoblasts is clearly changed in the stage of osteogenenic differentiation. We also found the novel signaling molecule to control the initial stage of mesenchymal stem cell differentiation into osteoblasts and adipocytes.

Research Products

• [Journal Article] Spleen tyrosine kinase influences the early stages of multilineage differentiation of bone marrow stromal cell lines by regulating phospholipase C gamma activities. (2018)
  • Author(s): Kusuyama J,, Kamisono A, ChangHwan S, Amir MS, Bandow K, Eiraku N, Ohnishi T, Matsuguchi T.
  • Journal Title: J Cell Physiol. Volume: 233 Issue: 3 Pages: 2549-2559
  • DOI: 10.1002/jcp.26130
  • Peer Reviewed
• [Journal Article] Constitutive activation of p46JNK2 is indispensable for C/EBPδ induction in the initial stage of adipogenic differentiation. (2017)
  • Author(s): Kusuyama J, Ohnishi T, Bandow K, Amir MS, Shima K, Semba I, Matsuguchi T.
  • Journal Title: Biochem J. Volume: 474 Issue: 20 Pages: 3421-3437
  • DOI: 10.1042/bcj20170332
  • Peer Reviewed
• [Journal Article] Lymphomatoid granulomatosis initially presenting as ulcerated subcutaneous and muscle lesions without pulmonary involvement (2017)
  • Author(s): Higashi Y, Yoshioka T, Kawai K, Fujii K, Yoshimitsu M, Kusuyama J, Shima K, Tanimoto A, Kanekura T.
  • Journal Title: Journal of Dermatology Volume: 44 Issue: 5 Pages: 107-108
  • DOI: 10.1111/1346-8138.13712
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Osteopontin inhibits osteoblast responsiveness through the downregulation of focal adhesion kinase mediated by the induction of low molecular weight-protein tyrosine phosphatase. (2017)
  • Author(s): Kusuyama J., Bandow K., Ohnishi T., Hisadome M., Shima K., Semba I., Matsuguchi T.
  • Journal Title: Mol. Biol. Cell. Volume: Mar 22 Issue: 10 Pages: 10-07
  • DOI: 10.1091/mbc.e16-10-0716
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CXCL3 positively regulates adipogenic differentiation. (2016)
  • Author(s): Kusuyama J., Komorizono A., Bandow K., Ohnishi T., Matsuguchi T.
  • Journal Title: J. Lipid. Res. Volume: 57 Issue: 10 Pages: 1806-1820
  • DOI: 10.1194/jlr.m067207
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hepatocyte growth Factor reduces CXCL10 expression in keratinocytes. (2016)
  • Author(s): Hisadome M., Ohnishi T., Kakimoto K, Kusuyama J., Bandow K., Kanekura T., Matsuguchi T.
  • Journal Title: FEBS Letters Volume: 590 Issue: 20 Pages: 3595-3605
  • DOI: 10.1002/1873-3468.12452
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 低出力超音波（LIPUS）による 幹細胞の分化制御と組織再生能の向上 (2017)
  • Author(s): 楠山譲二
  • Organizer: 第90回超音波医学会学術集会
• [Presentation] 低出力超音波（LIPUS）による歯根膜由来幹細胞のBMP9誘導性骨分化及び炎症性応答の制御 (2017)
  • Author(s): 楠山譲二、中村利明、大西智和、榮樂菜保子、野口和行、松口徹也
  • Organizer: 第20回超音波骨折治療研究会
  • Place of Presentation: 品川インターシティホール（東京都・品川区）
• [Presentation] LIPUS刺激はNanogの発現誘導とリン酸化によって間葉系幹細胞の分化能を維持する (2016)
  • Author(s): 楠山譲二、成昌ファン、大西智和、坂東健二郎、松口徹也
  • Organizer: 第19回超音波骨折治療研究会
  • Place of Presentation: 品川インターシティホール（東京都港区）
  • Year and Date: 2016-01-23
• [Presentation] ケモカインCXCL3は脂肪分化を促進する (2016)
  • Author(s): 楠山譲二、小森園杏奈、坂東健二郎、大西智和、松口徹也
  • Organizer: 平成28年度日本生化学会九州支部例会
  • Place of Presentation: 稲盛会館（鹿児島県・鹿児島市）
• [Presentation] JNKシグナリングは骨芽細胞の多様性分化を制御する (2016)
  • Author(s): 楠山譲二、大西智和、松口徹也
  • Organizer: 第34回日本骨代謝学会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
• [Presentation] 低出力超音波（LIPUS）は歯根膜由来幹細胞のBMP9誘導性骨分化を促進し炎症応答を防ぐ (2016)
  • Author(s): 楠山譲二、中村利明、大西智和、榮樂菜保子、野口和行、松口徹也
  • Organizer: 第25回硬組織再生生物学会
  • Place of Presentation: 日本大学歯学部（東京都・千代田区）
• [Presentation] JNKシグナリングは骨芽細胞の多様性分化を制御する (2016)
  • Author(s): 楠山譲二、大西智和、松口徹也
  • Organizer: 第58回歯科基礎医学会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
• [Presentation] 低出力超音波（LIPUS）による歯根膜由来幹細胞のBMP9誘導性骨分化及び炎症性応答の制御 (2016)
  • Author(s): 楠山譲二、中村利明、大西智和、榮樂菜保子、野口和行、松口徹也
  • Organizer: 第15回日本超音波治療研究会
  • Place of Presentation: 東京女子医科大学・早稲田大学連携先端生命 医科学研究教育施設（東京都・千代田区）
• [Presentation] 低出力超音波刺激(LIPUS)は間葉系幹細胞の多継代培養による分化能喪失を防ぐ (2015)
  • Author(s): 楠山譲二、成昌ファン、仙波伊知郎、松口徹也
  • Organizer: 第14回日本超音波治療研究会
  • Place of Presentation: 高知市文化プラザかるぽーと（高知県高知市）
  • Year and Date: 2015-11-28
• [Presentation] LIPUS（低出力超音波）による間葉系幹細胞の分化能維持 (2015)
  • Author(s): 楠山譲二、仙波伊知郎、松口徹也
  • Organizer: 第24回硬組織再生生物学会
  • Place of Presentation: 大阪歯科大学（大阪府牧方市）
  • Year and Date: 2015-08-22