The elucidation of osteoporosis treatment targeting RNA-binding protein Musashi2 in osteoclast

• Project/Area Number: 18K16626
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kyushu University
• Principal Investigator: Fujiwara Toshifumi 九州大学, 大学病院, 助教 (20644800)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: Musashi / 破骨細胞 / 骨粗鬆症 / Notchシグナル / 骨代謝

Outline of Final Research Achievements

During osteoclast differentiation, expression of the RNA-binding protein Musashi (Msi) is increased, and cell survival is regulated by Notch signaling, Notch2 and Hes1. Msi has 1 and 2 isoforms, and it is necessary to evaluate the function of both Msi1 and Msi2 in osteoclasts. Msi1 and 2 knockout mice were generated by LysM-Cre mice that selectively knockout (cKO) from monocytic cells with Msi1 and 2 Flox mice. Bone mass in the lumbar spine and femur was analyzed by micro-CT at 2 months age in 5 male and female control (Con) and 5 cKO mice, each. There was no significant difference.

Academic Significance and Societal Importance of the Research Achievements

超高齢社会に伴い、骨粗鬆症患者は急増している。骨粗鬆性骨折は患者の日常生活動作を著しく低下させ、医療費・介護費の上昇で医療経済を圧迫している。そのため、骨吸収を行う破骨細胞を制御する薬剤開発は急務であり、破骨細胞を中心とする骨代謝機構を詳細に解明する必要がある。
本研究ではその一端を担うMusashi遺伝子の役割について解析を行った。

Research Products

• [Journal Article] Protocol for the 2ND-STEP study, Japan Clinical Oncology Group study JCOG1802: a randomized phase II trial of second-line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib (2023)
  • Author(s): Endo Makoto、Kataoka Tomoko、Fujiwara Toshifumi、(abbrev)、Oda Yoshinao、Ozaki Toshifumi、Tanaka Kazuhiro
  • Journal Title: BMC Cancer Volume: 23 Issue: 1 Pages: 219-219
  • DOI: 10.1186/s12885-023-10693-w
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of bone density and skeletal muscle mass after sleeve gastrectomy using computed tomography method (2023)
  • Author(s): Kai Kazuhiro、Fujiwara Toshifumi、Nagao Yoshihiro、Oki Eiji、Yoshizumi Tomoharu、Eto Masatoshi、Nakashima Yasuharu
  • Journal Title: Bone Reports Volume: 18 Pages: 101661-101661
  • DOI: 10.1016/j.bonr.2023.101661
  • Peer Reviewed / Open Access
• [Journal Article] Is there a reduction in hip destruction under a treat-to-target strategy in patients with rheumatoid arthritis? (2023)
  • Author(s): Tsushima Hidetoshi、Takahide Sakuragi、Akasaki Yukio、Fujiwara Toshifumi、Hara Daisuke、Ikemura Satoshi、Sakuraba Kouji、Kamura Satoshi、Miyahara Hisaaki、Yamada Hisakata、Fukushi Jun-ichi、Nakashima Yasuharu
  • Journal Title: Modern Rheumatology Volume: 14 Issue: 2 Pages: 334-339
  • DOI: 10.1093/mr/road021
  • Peer Reviewed
• [Journal Article] Expression of SATB2, RUNX2, and SOX9 and possible osteoblastic and chondroblastic differentiation in chondroblastoma (2023)
  • Author(s): Toda Yu、Yamamoto Hidetaka、Iwasaki Takeshi、Ishihara Shin、Ito Yoshihiro、Susuki Yosuke、Kawaguchi Kengo、Kinoshita Izumi、Kiyozawa Daisuke、Yamada Yuichi、Kohashi Kenichi、Kimura Atsushi、Fujiwara Toshifumi、Setsu Nokitaka、Endo Makoto、Matsumoto Yoshihiro、Nakashima Yasuharu、Mawatari Masaaki、Oda Yoshinao
  • Journal Title: Pathology - Research and Practice Volume: 241 Pages: 154239-154239
  • DOI: 10.1016/j.prp.2022.154239
  • Peer Reviewed
• [Journal Article] Postoperative clinical and functional outcomes in patients with tumor and tumor-like lesion of foot and ankle (2022)
  • Author(s): Kokubu Yasuhiko、Fujiwara Toshifumi、Nakagawa Koh、Setsu Nokitaka、Endo Makoto、Fukushi Jun-Ichi、Matsumoto Yoshihiro、Nakashima Yasuharu
  • Journal Title: Journal of Foot and Ankle Research Volume: 15 Issue: 1 Pages: 75-75
  • DOI: 10.1186/s13047-022-00582-z
  • Peer Reviewed / Open Access
• [Journal Article] Nuclear β-catenin translocation plays a key role in osteoblast differentiation of giant cell tumor of bone (2022)
  • Author(s): Kimura Atsushi、Toda Yu、Matsumoto Yoshihiro、Yamamoto Hidetaka、Yahiro Kenichiro、Shimada Eijiro、Kanahori Masaya、Oyama Ryunosuke、Fukushima Suguru、Nakagawa Makoto、Setsu Nokitaka、Endo Makoto、Fujiwara Toshifumi、Matsunobu Tomoya、Oda Yoshinao、Nakashima Yasuharu
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 13438-13438
  • DOI: 10.1038/s41598-022-17728-5
  • Peer Reviewed / Open Access
• [Journal Article] Transferrin receptor 1-mediated iron uptake regulates bone mass in mice via osteoclast mitochondria and cytoskeleton (2022)
  • Author(s): Das Bhaba K、Wang Lei、Fujiwara Toshifumi、Zhou Jian、Aykin-Burns Nukhet、Krager Kimberly J、Lan Renny、Mackintosh Samuel G、Edmondson Ricky、Jennings Michael L、Wang Xiaofang、Feng Jian Q、Barrientos Tomasa、Gogoi Jyoti、Kannan Aarthi、Gao Ling、Xing Weirong、Mohan Subburaman、Zhao Haibo
  • Journal Title: eLife Volume: 11
  • DOI: 10.7554/elife.73539
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical significance of signal regulatory protein alpha and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain expression in undifferentiated pleomorphic sarcoma (2022)
  • Author(s): Ishihara Shin、Iwasaki Takeshi、Kohashi Kenichi、Kawaguchi Kengo、Toda Yu、Fujiwara Toshifumi、Setsu Nokitaka、Endo Makoto、Matsumoto Yoshihiro、Nakashima Yasuharu、Oda Yoshinao
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: 1 Issue: 6 Pages: 1-1
  • DOI: 10.1007/s00432-022-04078-y
  • Peer Reviewed
• [Journal Article] Efficacy and safety of tranexamic acid in patients undergoing surgery for bone and soft tissue tumors: a propensity score matching analysis (2022)
  • Author(s): Oyama Ryunosuke、Setsu Nokitaka、Matsumoto Yoshihiro、Endo Makoto、Fujiwara Toshifumi、Iida Keiichiro、Nabeshima Akira、Nakashima Yasuharu
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 52 Pages: 1029-38
  • DOI: 10.1093/jjco/hyac078
  • Peer Reviewed
• [Journal Article] Clinical, Radiological, and Histopathological Characteristics of Periosteal Chondrosarcoma with a Focus on the Frequency of Medullary Invasion (2022)
  • Author(s): Nakagawa Makoto、Endo Makoto、Susuki Yosuke、Yokoyama Nobuhiko、Maekawa Akira、Nabeshima Akira、Iida Keiichiro、Fujiwara Toshifumi、Setsu Nokitaka、Matsunobu Tomoya、Matsumoto Yoshihiro、Yokoyama Ryohei、Yamada Yuichi、Kohashi Kenichi、Yamamoto Hidetaka、Oda Yoshinao、Iwamoto Yukihide、Nakashima Yasuharu
  • Journal Title: Journal of Clinical Medicine Volume: 11 Issue: 7 Pages: 2062-2062
  • DOI: 10.3390/jcm11072062
  • Peer Reviewed / Open Access
• [Journal Article] Methylation-mediated silencing of protein kinase C zeta induces apoptosis avoidance through ATM/CHK2 inactivation in dedifferentiated chondrosarcoma (2022)
  • Author(s): Shimada Eijiro、Matsumoto Yoshihiro、Nakagawa Makoto、Susuki Yosuke、Endo Makoto、Setsu Nokitaka、Fujiwara Toshifumi、Iida Keiichiro、Nabeshima Akira、Yahiro Kenichiro、Kimura Atsushi、Hirose Takeshi、Kanahori Masaya、Oyama Ryunosuke、Oda Yoshinao、Nakashima Yasuharu
  • Journal Title: British Journal of Cancer Volume: online ahead Issue: 9 Pages: 1289-1300
  • DOI: 10.1038/s41416-021-01695-1
  • Peer Reviewed
• [Journal Article] Factors affecting patient satisfaction related to cost and treatment effectiveness in rheumatoid arthritis: results from the multicenter observational cohort study, FRANK Registry (2022)
  • Author(s): Fujiwara Toshifumi、Kondo Masakazu、Yamada Hisakata、Fukushi Jun-ichi、Inoue Yasushi、Tsuru Tomomi、Shuto Toshihide、Yoshizawa Seiji、Miyamura Tomoya、Ayano Masahiro、Mitoma Hiroki、Arinobu Yojiro、Niiro Hiroaki、Hirata Akie、Hara Daisuke、Tsushima Hidetoshi、Akasaki Yukio、Ikemura Satoshi、Nakashima Yasuharu
  • Journal Title: Arthritis Research & Therapy Volume: 24 Issue: 1 Pages: 53-53
  • DOI: 10.1186/s13075-022-02746-5
  • Peer Reviewed / Open Access
• [Journal Article] The association between the expression of PD-L1 and CMTM6 in undifferentiated pleomorphic sarcoma (2021)
  • Author(s): Ishihara Shin、Oda Yoshinao、et al.
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: 147 Issue: 7 Pages: 2003-2011
  • DOI: 10.1007/s00432-021-03616-4
  • Peer Reviewed
• [Journal Article] Clinical benefits of vessel sealing system (LigaSure?) during surgery for soft tissue sarcoma: a propensity score matching analysis (2021)
  • Author(s): Shimada Eijiro、Matsumoto Yoshihiro、Endo Makoto、Setsu Nokitaka、Fujiwara Toshifumi、Yahiro Kenichiro、Kimura Atsushi、Nakashima Yasuharu
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 51 Issue: 8 Pages: 1242-1247
  • DOI: 10.1093/jjco/hyab083
  • Peer Reviewed
• [Journal Article] Risk factors for excessive postoperative sliding of femoral trochanteric fracture in elderly patients: A retrospective multicenter study (2021)
  • Author(s): Momii Kenta、Fujiwara Toshifumi、Mae Takao、Tokunaga Masami、Iwasaki Takeshi、Shiomoto Kyohei、Kubota Kensuke、Onizuka Toshihiro、Miura Tatsuhiko、Hamada Takahiro、Nakamura Tetsuro、Itokawa Takashi、Iguchi Takahiro、Yamashita Akihisa、Kikuchi Naoshi、Nakaie Kazutoshi、Matsumoto Yoshihiro、Nakashima Yasuharu
  • Journal Title: Injury Volume: 52 Issue: 11 Pages: 3369-3376
  • DOI: 10.1016/j.injury.2021.07.039
  • Peer Reviewed
• [Journal Article] Predictive factors of non-treatment and non-persistence to osteoporosis medication after fragility hip fractures at 3?years after discharge: a multicentre, prospective cohort study in the northern Kyushu district of Japan (2021)
  • Author(s): Kanahori Masaya、Matsumoto Yoshihiro、Fujiwara Toshifumi、Kimura Atsushi、Oyamada Akiko、Ohishi Masanobu、Ikuta Ko、Tsuchiya Kuniyoshi、Miyahara Hisaaki、Mae Takao、Hara Toshihiko、Saito Taichi、Arizono Takeshi、Kaji Kozo、Mawatari Taro、Fujiwara Masami、Takasaki Minoru、Iwamoto Yukihide、Nakashima Yasuharu
  • Journal Title: Archives of Osteoporosis Volume: 16 Issue: 1 Pages: 132-132
  • DOI: 10.1007/s11657-021-00988-5
  • Peer Reviewed
• [Journal Article] Does the Use of Peripheral Immune-Related Markers Indicate Whether to Administer Pazopanib, Trabectedin, or Eribulin to Advanced Soft Tissue Sarcoma Patients? (2021)
  • Author(s): Shimada Eijiro、Endo Makoto、Matsumoto Yoshihiro、Tsuchihashi Kenji、Ito Mamoru、Kusaba Hitoshi、Nabeshima Akira、Nawata Tomoya、Maekawa Akira、Matsunobu Tomoya、Setsu Nokitaka、Fujiwara Toshifumi、Iida Keiichiro、Nakagawa Makoto、Kohashi Kenichi、et al.
  • Journal Title: Journal of Clinical Medicine Volume: 10 Issue: 21 Pages: 4972-4972
  • DOI: 10.3390/jcm10214972
  • Peer Reviewed / Open Access
• [Journal Article] Frequency and risk factor analyses of bone erosion of the distal interphalangeal joint in patients with rheumatoid arthritis: a cross-sectional study (2021)
  • Author(s): Satoshi Ikemura, Satoshi Hagio, Yukio Akasaki, Toshifumi Fujiwara, Hidetoshi Tsushima, Yasuharu Nakashima
  • Journal Title: Acta Reumatologica portuguesa Volume: 46 Pages: 239-245
  • Peer Reviewed
• [Journal Article] Prognostic implication of desmoplastic stroma in synovial sarcoma: A histological review (2021)
  • Author(s): Toda Yu、Yamada Yuichi、Kohashi Kenichi、Ishihara Shin、Ito Yoshihiro、Susuki Yosuke、Kawaguchi Kengo、Kinoshita Izumi、Kiyozawa Daisuke、Mori Taro、Kuboyama Yusuke、Tateishi Yuki、Yamamoto Hidetaka、Fujiwara Toshifumi、Setsu Nokitaka、Endo Makoto、Matsumoto Yoshihiro、Nakashima Yasuharu、Mawatari Masaaki、Oda Yoshinao
  • Journal Title: Pathology - Research and Practice Volume: 228 Pages: 153668-153668
  • DOI: 10.1016/j.prp.2021.153668
  • Peer Reviewed
• [Journal Article] Histological and immunohistochemical features and genetic alterations in the malignant progression of giant cell tumor of bone: a possible association with TP53 mutation and loss of H3K27 trimethylation (2021)
  • Author(s): Ishihara Shin、Yamamoto Hidetaka、Iwasaki Takeshi、Toda Yu、Yamamoto Takeo、Yoshimoto Masato、Ito Yoshihiro、Susuki Yousuke、Kawaguchi Kengo、Kinoshita Izumi、Yamada Yuichi、Kohashi Kenichi、Fujiwara Toshifumi、Setsu Nokitaka、Endo Makoto、Matsumoto Yoshihiro、Kakuda Yuko、Nakashima Yasuharu、Oda Yoshinao
  • Journal Title: Modern Pathology Volume: - Issue: 5 Pages: 640-648
  • DOI: 10.1038/s41379-021-00972-x
  • Peer Reviewed
• [Journal Article] An Analysis of 20 Cases of Radiation-Associated Sarcoma, Including 4 Cases Treated by Carbon Ion Radiotherapy (2021)
  • Author(s): Negishi Takahito、Matsunobu Akira、Endo Makoto、Yokoyama Ryouhei、Kusano Shuhei、Furubayashi Nobuki、Taguchi Kenichi、Shioyama Yoshiyuki、Iida Keiichiro、Fujiwara Toshifumi、Setsu Nokitaka、Matsumoto Yoshihiro、Nakashima Yasuharu、Kohashi Kenichi、Yamamoto Hidetaka、Oda Yoshinao、Nakamura Motonobu
  • Journal Title: Oncology Volume: 100 Issue: 3 Pages: 148-154
  • DOI: 10.1159/000521504
  • Peer Reviewed
• [Journal Article] Autoreactivity of Peripheral Helper T Cells in the Joints of Rheumatoid Arthritis (2021)
  • Author(s): Sakuragi Takahide、Yamada Hisakata、Haraguchi Akihisa、Kai Kazuhiro、Fukushi Jun-ichi、Ikemura Satoshi、Akasaki Yukio、Fujiwara Toshifumi、Tsushima Hidetoshi、Tsutsui Tomoko、Kondo Masakazu、Yoshikai Yasunobu、Okada Seiji、Nakashima Yasuharu
  • Journal Title: The Journal of Immunology Volume: 4 Issue: 9 Pages: 2000783-2000783
  • DOI: 10.4049/jimmunol.2000783
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Shape Factor of the Spinal Cord: A Possible Predictor of Surgical Outcome for Intradural Extramedullary Spinal Tumors in the Thoracic Spine (2021)
  • Author(s): Matsumoto Yoshihiro、Saiwai Hirokazu、Iida Keiichiro、Okada Seiji、Endo Makoto、Setsu Nokitaka、Fujiwara Toshifumi、Kawaguchi Kenichi、Nakashima Yasuharu
  • Journal Title: Global Spine Journal Volume: 1 Issue: 7 Pages: 098257-098257
  • DOI: 10.1177/2192568220982571
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Risk Factors of Periprosthetic Infection in Patients with Tumor Prostheses Following Resection for Musculoskeletal Tumor of the Lower Limb (2020)
  • Author(s): Fujiwara Toshifumi、Ebihara Toshihiro、Kitade Kazuki、Setsu Nokitaka、Endo Makoto、Iida Keiichiro、Matsumoto Yoshihiro、Matsunobu Tomoya、Oda Yoshinao、Iwamoto Yukihide、Nakashima Yasuharu
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 10 Pages: 3133-3133
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• [Journal Article] Activation of TLR4 Signaling Inhibits Progression of Osteosarcoma by Stimulating CD8-positive Cytotoxic Lymphocytes. (2020)
  • Author(s): Yahiro K, Matsumoto Y, Yamada H, Endo M, Setsu N, Fujiwara T, Nakagawa M, Kimura M, Shimada E, Okada S, Oda Y, Nakashima Y.
  • Journal Title: Cancer Immunol Immunother Volume: - Issue: 5 Pages: 745-758
  • DOI: 10.1007/s00262-020-02508-9
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• [Journal Article] Prognostic factors for the short-term mortality of patients with rheumatoid arthritis admitted to intensive care units (2020)
  • Author(s): Fujiwara Toshifumi、Tokuda Kentaro、Momii Kenta、Shiomoto Kyohei、Tsushima Hidetoshi、Akasaki Yukio、Ikemura Satoshi、Fukushi Jun-ichi、Maki Jun、Kaku Noriyuki、Akahoshi Tomohiko、Taguchi Tomoaki、Nakashima Yasuharu
  • Journal Title: BMC Rheumatology Volume: 4 Issue: 1 Pages: 3133-3133
  • DOI: 10.1186/s41927-020-00164-1
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• [Journal Article] Predictive factors of mortality of patients with fragility hip fractures at 1 year after discharge: A multicenter, retrospective study in the northern Kyushu district of Japan (2019)
  • Author(s): Kimura Atsushi, Matsumoto Yoshihiro, Wakata Yoshifumi, Oyamada Akiko, Ohishi Masanobu, Fujiwara Toshifumi, et. al
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• [Journal Article] Selective inhibition of mutant IDH1 by DS-1001b ameliorates aberrant histone modifications and impairs tumor activity in chondrosarcoma (2019)
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• [Journal Article] Mid-term clinical outcome of constrained condylar knee prosthesis for patients with rheumatoid arthritis (2018)
  • Author(s): Fujiwara T, Fujimura K, Hamai S, Kamura S, Nakashima Y, Miyahara H
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• [Journal Article] The Tamoxifen Derivative Ridaifen-B is a High Affinity Selective CB2 Receptor Inverse Agonist Exhibiting Anti-Inflammatory and Anti-Osteoclastogenic Effects (2018)
  • Author(s): Franks LN, Ford BM, Fujiwara T, Zhao H, Prather PL
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• [Journal Article] Deletion of ferroportin in murine myeloid cells increases iron accumulation and stimulates osteoclastogenesis in vitro and in vivo (2018)
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  • DOI: 10.1074/jbc.ra117.000834
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• [Presentation] 骨髄性細胞におけるFerroportin欠失は細胞内鉄貯蔵を増加させ、破骨細胞分化を誘導する (2019)
  • Author(s): 藤原 稔史, Lei Wang, Bin Fang, 中島 康晴, Zhao Haibo
  • Organizer: 第３７回日本骨代謝学会
• [Presentation] LIS1はM-CSF・RANKLシグナルとCDC42を介して破骨細胞分化を制御する (2019)
  • Author(s): 藤原 稔史, Ye Shiqiao, 中島 康晴, Zhao Haibo
  • Organizer: 第5回日本骨免疫学会