Mechanism of heterotopic ossification in human spinal ligament and skin tissues of patient with ossification of spinal ligaments

• Project/Area Number: 23592152
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Hirosaki University
• Principal Investigator: NUMASAWA Takuya 弘前大学, 医学(系)研究科(研究院), 研究員 (80396407)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2012: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 幹細胞 / 靱帯 / 皮膚 / 異所性骨化

Research Abstract

We isolated and expanded MSCs from human spinal ligaments and demonstrated localization of MSCs in spinal ligaments. Immunolocalization of MSCs was observed in the perivascular area and collagenous matrix in spinal ligaments.
We also isolated and expanded MSCs from human skin tissue. We showed that the osteogenic differentiation potential was significantly higher in MSCs from OPLL patients than in those from non-OPLL patients in both spinal ligament and skin tissues. Osteogenic-related gene expressions were significantly higher in the OPLL group than in the non-OPLL group. These findings suggest an increase in the osteogenic differentiation potential of MSCs from OPLL patients and that this propensity toward the osteogenic lineage may be a causal factor in the ossification in these ligaments.

Research Products

• [Journal Article] Osteogenic lineage commitment of mesenchymal stem cells from patients with ossification of the posterior longitudinal ligament. (2014)
  • Author(s): Yoshifumi Harada
  • Journal Title: Biochem Biophis Res Commun. Volume: 443(3) Issue: 3 Pages: 1014-20
  • DOI: 10.1016/j.bbrc.2013.12.080
  • Peer Reviewed
• [Journal Article] Interobserver and intraobserver reliability of the classification and diagnosis for ossification of the posterior longitudinal ligament of the cervical spine (2013)
  • Author(s): Kudo H, Yokoyama T, Tsushima E, Ono A, Numasawa T, Wada K, Tanaka S, Toh S
  • Journal Title: Eur Spine J Volume: 22(1) Pages: 205-10
• [Journal Article] Genetic Study Group of Investigation Committee on Ossification of the Spinal Ligaments,genome-wide sib-pair linkage analysis of ossification of the posterior longitudinal ligament of the spine (2013)
  • Author(s): Karasugi T, Nakajima M, Ikari K; , Tsuji T, Matsumoto M, Chiba K, Uchida K, Kawaguchi Y, Mizuta H, Ogata N, Iwasaki M, Maeda S, Numasawa T, Abumi K, Kato T, Ozawa H, Taguchi T, Kaito T, Neo M, Yamazaki M, Tadokoro N, Yoshida M, Nakahara S, Endo K, Imagama S, Demura S, Sato K, Seichi A, Ichimura S, Watanabe M, Watanabe K, Nakamura Y, Mori K, Baba H, Toyama Y, Ikegawa S
  • Journal Title: J Bone Miner Metab Volume: 31(2) Pages: 136-43
• [Journal Article] A genome-wide sib-pair linkage analysis of Ossification of the posterior longitudinal ligament of the spine (2013)
  • Author(s): Tatsuki Karasugi
  • Journal Title: J Bone Miner Metab. Volume: 31 Issue: 2 Pages: 136
  • DOI: 10.1007/s00774-012-0404-y
  • NAID: 10031168848
  • Peer Reviewed
• [Journal Article] Interobserver and intraobserver reliability of the classification and diagnosis for ossification of the posterior longitudinal ligament of the cervical spine. (2013)
  • Author(s): Hitoshi Kudo
  • Journal Title: Eur Spine J. Volume: 22(1) Issue: 1 Pages: 2015-10
  • DOI: 10.1007/s00586-012-2573-8
  • Peer Reviewed
• [Journal Article] Immunohistochemical localization of mesenchymal stem cells in ossified human spinal ligaments. (2013)
  • Author(s): Shunfu Chin
  • Journal Title: Biochem Biophis Res Commun. Volume: 436(4) Issue: 4 Pages: 698-704
  • DOI: 10.1016/j.bbrc.2013.06.019
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cell isolation and characterization from human spinal ligaments (2012)
  • Author(s): Asari T, Furukawa K, Tanaka S, Kudo H, Mizukami H, Ono A, Numasawa T, Kumagai G, Motomura S, Yagihashi S, Toh S
  • Journal Title: Biochem Biophys Res Commun Volume: 417(4) Pages: 1193-9
• [Journal Article] Simple foot tapping test as a quantitative objective assessment of cervical myelopathy (2012)
  • Author(s): Numasawa T, Ono A, Wada K, Yamasaki Y, Yokoyama T, Aburakawa S, Takeuchi K, Kumagai G, Kudo H, Umeda T, Nakaji S, Toh S
  • Journal Title: Spine (Phila Pa 1976). Volume: 37(2) Pages: 108-13
  • NAID: 10030903583
• [Journal Article] Simple Foot Tapping Test as a Quantitative Objective Assessment of Cervical Myelopathy (2012)
  • Author(s): Numasawa Takuya
  • Journal Title: Spine (Phila Pa 1976). Volume: 37 Issue: 2 Pages: 108-113
  • DOI: 10.1097/brs.0b013e31821041f8
  • NAID: 10030903583
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cell isolation and characterization from human spinal ligaments (2012)
  • Author(s): Toru Asari
  • Journal Title: Biochem Biophys Res Commun Volume: 27 Issue: 4 Pages: 1193-1199
  • DOI: 10.1016/j.bbrc.2011.12.106
  • Peer Reviewed
• [Journal Article] The relationship between the anatomy of the nuchal ligament and postoperative axial pain after cervical laminoplasty: cadaver and clinical study (2012)
  • Author(s): Atsushi Ono
  • Journal Title: Spine Volume: 37 Issue: 26 Pages: 1607-1013
  • DOI: 10.1097/brs.0b013e318274101b
  • Peer Reviewed
• [Journal Article] Genetic differences in the osteogenic differentiation potency according to the classification of ossification of the posterior longitudinal ligament of the cervical spine (2011)
  • Author(s): Kudo H, Furukawa K, Yokoyama T, Ono A, Numasawa T, Wada K, Tanaka S, Asari T, Ueyama K, Motomura S, Toh S
  • Journal Title: Spine (Phila Pa 1976) Volume: 36(12) Pages: 951-7
  • NAID: 10030714642
• [Presentation] 骨粗鬆症性脊椎椎体骨折に対する初期安静治療による椎体変化 (2013)
  • Author(s): 沼沢拓也
  • Organizer: 日本脊椎脊髄病学会
  • Place of Presentation: 沖縄
• [Presentation] 脊柱靱帯骨化症における間葉系幹細胞の局在および制御因子発現の免疫組織学的検討 (2013)
  • Author(s): 陳俊輔
  • Organizer: 日本整形外科基礎学術集会
  • Place of Presentation: 千葉
• [Presentation] 頚椎後縦靱帯骨化症患者由来間葉系幹細胞の骨分化能に関連する因子の検討 (2013)
  • Author(s): 原田義史
  • Organizer: 日本整形外科基礎学術集会
  • Place of Presentation: 千葉
• [Presentation] 脊柱靱帯骨化症患者では脊柱靱帯由来間葉系幹細胞の骨分化能が高い (2012)
  • Author(s): 原田義史、沼沢拓也
  • Organizer: 第27回日本整形外科基礎学術集会
  • Place of Presentation: 名古屋市
• [Presentation] ヒト脊柱靱帯由来間葉系幹細胞の分離方法による違いの検討 (2012)
  • Author(s): 浅利亨、沼沢拓也
  • Organizer: 第27回日本整形外科基礎学術集会
  • Place of Presentation: 名古屋市
• [Presentation] Association between radiological cervical degeneration and daily living neck function and pain in the community (2011)
  • Author(s): 沼沢拓也
  • Organizer: Annual meeting of Eurospine
  • Place of Presentation: Milan