Regulatory molecular mechanism of calcification on osteoblastic differentiation of human mesenchymal stem cells in vitro

• Project/Area Number: 16K10915
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Niimi College
• Principal Investigator: Sasaki Junzo 新見公立大学, 健康科学部, 教授(移行) (30093686)
• Co-Investigator(Kenkyū-buntansha): 藤田 洋史 岡山大学, 医歯薬学総合研究科, 助教 (20423288) ; 岡 剛史 岡山大学, 医歯薬学総合研究科, 講師 (50160651) ; 瀧川 朋亨 岡山大学, 大学病院, 助教 (80613166)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 石灰化 / 骨芽細胞 / 間葉系幹細胞 / 死細胞 / 血清 / 質量分析 / 分化

Outline of Final Research Achievements

It is believed that osteoblasts induced bone mineralization via release of matrix vesicle. We reported that necrotic and apoptotic cells also serve as nuclei for calcification on osteoblastic differentiation of human mesenchymal stem cells (hMSC) in vitro. In this study, we investigated regulatory molecular mechanism of calcification on osteoblastic differentiation of hMSC in vitro. We identified various molecules binding to necrotic dead cells under calcification medium containing fetal bovine serum using mass spectrometry. The gene cloning of calcification related candidates was performed. Overexpression of one of the candidates promoted the calcification on osteoblastic differentiation of hMSC in vitro suggesting that the molecule in serum has a role on calcification by osteoblasts.

Academic Significance and Societal Importance of the Research Achievements

血清中において石灰化を誘導する分子を同定することで、新たな石灰化制御タンパク質の証拠を提示する重要な意義を持つ。また、動脈硬化や軟骨内骨化における石灰化においても、本研究にて明らかになった分子の関連が予想され、骨粗鬆症や骨形成不全症の改善や、異所性石灰化の治療にも応用できる可能性がある。

Research Products

• [Journal Article] Glutathione accelerates osteoclast differentiation and inflammatory bone destruction (2019)
  • Author(s): Fujita Hirofumi、Ochi Masahiko、Ono Mitsuaki、Aoyama Eriko、Ogino Tetsuya、Kondo Yoichi、Ohuchi Hideyo
  • Journal Title: Free Radical Research Volume: 53 Issue: 2 Pages: 226-236
  • DOI: 10.1080/10715762.2018.1563782
  • Peer Reviewed
• [Journal Article] Early response assessment of re-ossification after palliative conventional radiotherapy for vertebral bone metastases (2019)
  • Author(s): Nakata Eiji、Sugihara Shinsuke、Kataoka Masaaki、Yamashita Natsumi、Furumatsu Takayuki、Takigawa Tomoyuki、Tetsunaga Tomoko、Ozaki Toshifumi
  • Journal Title: Journal of Orthopaedic Science Volume: 24 Issue: 2 Pages: 332-336
  • DOI: 10.1016/j.jos.2018.08.018
  • Peer Reviewed
• [Journal Article] Metabolic abnormalities in adult T-cell leukemia/lymphoma and induction of specific leukemic cell death using photodynamic therapy (2018)
  • Author(s): Takashi Oka, Hajime Mizuno, Masumi Sakata, Hirofumi Fujita, Tadashi Yoshino,Yoshihisa Yamano, Kozo Utsumi, Tsutomu Masujima & Atae Utsunomiya
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 14979-14979
  • DOI: 10.1038/s41598-018-33175-7
  • Peer Reviewed / Open Access
• [Journal Article] Merkel cell polyomavirus and Langerhans cell neoplasm. (2018)
  • Author(s): Murakami I, Wada N, Nakashima J, Iguchi M, Toi M, Hashida Y, Higuchi T, Daibata M, Matsushita M, Iwasaki T, Kuwamoto S, Horie Y, Nagata K, Hayashi K, Oka T, Yoshino T, Imamura T, Morimoto A, Imashuku S, Gogusev J, Jaubert F.
  • Journal Title: Cell Commun Signal. Volume: 16(1) Issue: 1 Pages: 49-49
  • DOI: 10.1186/s12964-018-0261-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relationship between Displacement of the Psoas Major Muscle and Spinal Alignment in Patients with Adult Spinal Deformity (2018)
  • Author(s): Oda Yoshiaki、Takigawa Tomoyuki、Ugawa Ryo、Shiozaki Yasuyuki、Misawa Haruo、Sugimoto Yoshihisa、Tanaka Masato、Ozaki Toshifumi
  • Journal Title: Asian Spine Journal Volume: 12 Issue: 2 Pages: 335-335
  • DOI: 10.4184/asj.2018.12.2.335
  • Peer Reviewed
• [Journal Article] Gene expression analysis of hypersensitivity to mosquito bite, chronic active EBV infection and NK/T-lymphoma/leukemia (2017)
  • Author(s): Kana Washio, Takashi Oka, Lamia Abdalkader, Michiko Muraoka, Akira Shimada, Megumi Oda, Hiaki Sato, Katsuyoshi Takata, Yoshitoyo Kagami, Norio Shimizu, Seiichi Kato, Hiroshi Kimura, Kazunori Nishizaki, Tadashi Yoshino & Hirokazu Tsukahara
  • Journal Title: Leukemia & Lymphoma Volume: 58 Issue: 11 Pages: 1-12
  • DOI: 10.1080/10428194.2017.1304762
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Discrimination between Malignant and Benign Vertebral Fractures Using Magnetic Resonance Imaging (2017)
  • Author(s): Takigawa Tomoyuki、Tanaka Masato、Sugimoto Yoshihisa、Tetsunaga Tomoko、Nishida Keiichiro、Ozaki Toshifumi
  • Journal Title: Asian Spine J. Volume: 11 Issue: 3 Pages: 478-478
  • DOI: 10.4184/asj.2017.11.3.478
• [Journal Article] Denosumab and alendronate treatment in patients with back pain due to fresh osteoporotic vertebral fractures (2017)
  • Author(s): Tetsunaga Tomoko、Tetsunaga Tomonori、Nishida Keiichiro、Tanaka Masato、Sugimoto Yoshihisa、Takigawa Tomoyuki、Takei Yoshitaka、Ozaki Toshifumi
  • Journal Title: J Orthop Sci. Volume: 22 Issue: 2 Pages: 230-236
  • DOI: 10.1016/j.jos.2016.11.017
• [Journal Article] Short-term outcomes of patients being treated for chronic intractable pain at a liaison clinic and exacerbating factors of prolonged pain after treatment (2017)
  • Author(s): Tetsunaga Tomoko、Tetsunaga Tomonori、Nishida Keiichiro、Tanaka Masato、Sugimoto Yoshihisa、Takigawa Tomoyuki、Ozaki Toshifumi
  • Journal Title: J Orthop Sci. Volume: 22 Issue: 3 Pages: 554-559
  • DOI: 10.1016/j.jos.2017.01.004
• [Journal Article] Phytoestrogen Suppresses Efflux of the Diagnostic Marker Protoporphyrin IX in Lung Carcinoma. (2016)
  • Author(s): Fujita H, Nagakawa K, Kobuchi H, Ogino T, Kondo Y, Inoue K, Shuin T, Utsumi T, Utsumi K, Sasaki J, Ohuchi H.
  • Journal Title: Cancer Res Volume: 76 Issue: 7 Pages: 1837-1846
  • DOI: 10.1158/0008-5472.can-15-1484
  • Peer Reviewed
• [Journal Article] Aberrant differential expression of EZH1 and EZH2 in Polycomb repressive complex 2 among B- and T/NK-cell neoplasms. (2016)
  • Author(s): Abdalkader L, Oka T, Takata K, Sato H, Murakami I, Otte AP, Yoshino T
  • Journal Title: Pathology Volume: vol.40 Issue: 5 Pages: 467-482
  • DOI: 10.1016/j.pathol.2016.05.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 石灰化誘導時における死細胞結合分子のプロテオーム解析 (2018)
  • Author(s): 藤田洋史、佐々木順造
  • Organizer: 第71回日本酸化ストレス学会 第18回日本NO学会合同学術集会
• [Presentation] マウス骨髄マクロファージにおけるRANKLによる破骨細胞分化に対するGlutathioneの影響 (2018)
  • Author(s): 藤田 洋史、大野 充昭、青山 絵理子、荻野哲也、大内 淑代
  • Organizer: 第71回日本酸化ストレス学会第18回日本NO学会合同学術集会
• [Presentation] 破骨細胞におけるロイコトリエン系の機能解明：CRISPR-Cas9を用いたalox5apノックアウトマウスの作製 (2018)
  • Author(s): 藤田 洋史、長尾 僚祐、土生田宗憲、服部 高子、久保田 聡、大内 淑代
  • Organizer: 第91回日本生化学会大会
• [Presentation] 破骨細胞におけるロイコトリエン系の機能解析：CRISPR-Cas9を用いたcysltr1ノックアウトマウスの作製 (2018)
  • Author(s): 藤田 洋史、土生田宗憲、服部 高子、久保田 聡、大内 淑代
  • Organizer: 第124回日本解剖学会総会・全国学術集会
• [Presentation] ラット顎下腺における活性酸素合成酵素の発現 (2017)
  • Author(s): 安部仁晴、中川敏浩、佐々木順造、渡邊弘樹
  • Organizer: 第122回日本解剖学会総会・学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-28
• [Presentation] Sensitive detection of dynamic changes of metabolic abnormalities during onset and progression of adult T-cell leukemia/lymphoma (ATL) and induction of specific leukemic cell death by photodynamic action. (2017)
  • Author(s): Takashi Oka, Masumi Sakata, Hajime Mizuno, Hirofumi Fujita, Tsutomu Masujima, Tadashi Yoshino, Yoshihisa Yamano and Atae Utsunomiya
  • Organizer: The18th International Conference on Human Retrovirology: HTLV and Related Viruses HTLV.
  • Place of Presentation: Tokyo
  • Year and Date: 2017-03-07
• [Presentation] ラット顎下腺における活性酸素合成酵素の発現 (2017)
  • Author(s): 安部仁晴, 中川敏浩, 佐々木順造, 渡邊弘樹
  • Organizer: 第122回日本解剖学会総会・全国学術集会
• [Presentation] 感染対策チームメンバーのチームプロセスに関連する要因 (2017)
  • Author(s): 山本智恵子, 矢嶋裕樹, 大月説子, 土井英子, 佐々木順造
  • Organizer: 第11回看護教育研究発表会
• [Presentation] 植物性エストロゲンはガン診断マーカープロトポルフィリンIXの排出を抑制する (2017)
  • Author(s): 藤田 洋史, 永川 恵介, 小渕 浩嗣, 荻野 哲也, 近藤 洋一, 井上 啓史, 執印 太郎, 内海 俊彦, 内海 耕慥, 佐々木 順造, 大内 淑代
  • Organizer: 第114回岡山医学会総会
• [Presentation] 成人T細胞白血病/リンパ腫（ATL）を発症したHTLV-1キャリアにおける異常DNAメチル化の解析 (2017)
  • Author(s): 佐藤妃映、岡 剛史、神農陽子、鷲尾佳奈、村上一郎、大内田守、宇都宮與、吉野 正
  • Organizer: 第57回日本リンパ網内系学会総会
• [Presentation] 成人T細胞白血病/リンパ腫（ATL）におけるDNA異常メチル化と病態の変動との関連 (2017)
  • Author(s): 佐藤妃映、岡 剛史、神農陽子、鷲尾佳奈、村上一郎、大内田守、宇都宮與、吉野 正
  • Organizer: 第106回日本病理学会総会
• [Presentation] インストゥルメンテーション後の再手術の検討 (2017)
  • Author(s): 瀧川朋亨
  • Organizer: 脊椎インストゥメンテーション学会
• [Presentation] 思春期特発性側弯症患者の 自己イメージ (2017)
  • Author(s): 瀧川朋亨
  • Organizer: 第46回日本脊椎脊髄病学会
• [Presentation] ヘム代謝制御に基づく光感受性物質protoporphyrin IX蓄積機構の研究 (2016)
  • Author(s): 藤田 洋史, 永川 恵介, 小渕 浩嗣, 荻野 哲也, 近藤 洋一, 井上 啓史, 執印 太郎, 内海 俊彦, 内海 耕慥, 佐々木 順造, 大内 淑代
  • Organizer: 第69回日本酸化ストレス学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-08-30