Roles of Runx2 and Runx3 in cartilage degeneration

• Project/Area Number: 25293316
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Jichi Medical University (2014-2015); The University of Tokyo (2013)
• Principal Investigator: TAKESHITA Katsushi 自治医科大学, 医学部, 教授 (30262009)
• Co-Investigator(Kenkyū-buntansha): SAITO Taku 東京大学, 医学部附属病院, 講師 (30456107) ; TAKETOMI Shuji 東京大学, 医学部附属病院, 講師 (70570018) ; 上原 浩介 東京大学, 医学部附属病院, 特任臨床医 (20599063)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 整形外科学 / 変形性関節症 / 軟骨細胞 / 骨軟骨代謝学

Outline of Final Research Achievements

We analyzed roles of transcription factor Runx2 and Runx3 in articular chondrocytes. First, we generated Runx2-flox mice, and confirmed that the gene deletion was successful. We then crossed Runx2-flox mice with cartilage-specific Cre mice, and created osteoarthritis model. Deletion of these factors modified cartilage degeneration. We analyzed the molecular mechanisms by in vitro experiments.

Research Products

• [Journal Article] Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment. (2016)
  • Author(s): H. Aini, K. Itaka, A. Fujisawa, H. Uchida, S. Uchida, S. Fukushima, K. Kataoka, T. Saito, U. -I. Chung, S. Ohba
  • Journal Title: Sci. Rep. Volume: 6 Pages: 18743-18743
  • DOI: 10.1038/srep18743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability (2016)
  • Author(s): Chang SH, Yasui T, Taketomi S, Matsumoto T, Kim-Kaneyama JR, Omiya T, Hosaka Y, Inui H, Omata Y, Yamagami R, Mori D, Yano F, Chung U, Tanaka S, Saito T.
  • Journal Title: Osteoarthritis Cartilage. Volume: (4) Pages: 688-697
  • DOI: 10.1016/j.joca.2015.11.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Predictive Factors for Subjective Improvement in Lumbar Spinal Stenosis Patients with Nonsurgical Treatment: A 3-Year Prospective Cohort Study. (2016)
  • Author(s): Matsudaira K, Hara N, Oka H, Kunogi J, Yamazaki T, Takeshita K, Atsushi S, Tanaka S.
  • Journal Title: PLoS One Volume: 11
  • DOI: 10.1371/journal.pone.0148584
  • Peer Reviewed
• [Journal Article] <b>Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem </b><b>cells </b> (2015)
  • Author(s): Saito T, Yano F, Mori D, Kawata M, Hoshi K, Takato T, Masaki H, Otsu M, Eto K, Nakauchi H, Chung UI, Tanaka S
  • Journal Title: Biomed. Res. Volume: 36 Issue: 3 Pages: 179-186
  • DOI: 10.2220/biomedres.36.179
  • NAID: 130005083858
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Matsubayashi Y, Takeshita K, Sumitani M, Oshima Y, Tonosu J, Kato S, Ohya J, Oichi T, Okamoto N, Tanaka S. PLoS One. 201 (2015)
  • Author(s): Psychometric Validation of the Japanese Version of the Neuropathic Pain Symptom Inventory.
  • Journal Title: PLoS One Volume: 10
  • DOI: 10.1371/journal.pone.0143350
  • Peer Reviewed
• [Journal Article] Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2 (2015)
  • Author(s): Sugita S, Taketomi S, Saito T, et al.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 112 Pages: 3080-3085
  • DOI: 10.1073/pnas.1419699112
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] <b>Regulation of mouse chondrocyte differentiation by CCAAT/enhancer-binding pr</b><b>oteins </b> (2015)
  • Author(s): Okuma T, Hirata M, Yano F, Mori D, Kawaguchi H, Chung UI, Tanaka S, Saito T
  • Journal Title: Biomed. Res. Volume: 36 Issue: 1 Pages: 21-29
  • DOI: 10.2220/biomedres.36.21
  • NAID: 130004903876
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison of the Japanese Orthopaedic Association (JOA) Score and Modified JOA (mJOA) Score for the Assessment of Cervical Myelopathy: A Multicenter Observational Study. (2015)
  • Author(s): Kato S, Takeshita K, et al.
  • Journal Title: PLoS One Volume: 10
  • DOI: 10.1371/journal.pone.0123022
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Elevated Levels of Phosphorylated Neurofilament Heavy Subunit in the Cerebrospinal Fluid of Patients with Lumbar Spinal Stenosis (2015)
  • Author(s): Ohya J, Takeshita K, et al.
  • Journal Title: Spine J. Volume: 未定 Pages: 1587-1592
  • DOI: 10.1016/j.spinee.2015.03.013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Patient satisfaction with double-door laminoplasty for cervical compression myelopathy. (2015)
  • Author(s): Ohya J, Takeshita K, et al.
  • Journal Title: J Orthop Sci Volume: 20 Pages: 64-70
  • DOI: 10.1007/s00776-014-0666-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of SCAN Domain Zinc-Finger Gene ZNF449 as a Novel Factor of Chondrogenesis (2014)
  • Author(s): Okada K, Saito T, et al.
  • Journal Title: PLoS One Volume: 9
  • DOI: 10.1371/journal.pone.0115169
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Disease-modifying effects of TD-198946 on progressed osteoarthritis in a mouse model (2014)
  • Author(s): Yano F, Saito T, et al.
  • Journal Title: Ann Rheum Dis Volume: 73 Pages: 2062-2064
  • DOI: 10.1136/annrheumdis-2014-205672
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Morphological characteristics of cervical spine in patients with athetoid cerebral palsy and the accuracy of pedicle screw placement. (2014)
  • Author(s): Kato S, Takeshita K, et al.
  • Journal Title: Spine Volume: 39
  • DOI: 10.1097/brs.0000000000000234
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of fibroblast growth factor-18 as a molecule to protect adult articular cartilage by gene expression profiling (2014)
  • Author(s): Mori Y, Saito T, Chang SH, Kobayashi H, Ladel CH, Guehring H, Chung UI, Kawaguchi H.
  • Journal Title: J Biol Chem. Volume: 289 Pages: 10192-200
  • DOI: 10.1074/jbc.m113.524090
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] NF-kB/TNF-a positive feedback loop with active proteasome machinery supports myeloid leukemia initiating cell capacity. (2014)
  • Author(s): Kagoya Y, Yoshimi A, Kataoka K, Nakagawa M, Kumano K, Arai S, Kobayashi H, Saito T, Iwakura Y, Kurokawa M.
  • Journal Title: Journal of Clinical Investigation Volume: 124 Pages: 528-42
  • DOI: 10.1172/jci68101
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Generation of Col2a1-EGFP-iPS cells for monitoring chondrogenic differentiation. (2014)
  • Author(s): Saito T, Yano F, Mori D, Ohba S, Hojo H, Otsu M, Eto K, Nakauchi H, Tanaka S, Chung UI, Kawaguchi H
  • Journal Title: PLoS ONE Volume: 16;8(9)
  • DOI: 10.1371/journal.pone.0074137
  • Peer Reviewed
• [Journal Article] Transcriptional induction of ADAMTS5 by an NF-κB family member RelA/p65 in chondrocytes during osteoarthritis development. (2013)
  • Author(s): Kobayashi H, Hirata M, Saito T, Itoh S, Chung UI, Kawaguchi H.
  • Journal Title: J Biol Chem Volume: 288 Pages: 28620-28629
  • DOI: 10.1074/jbc.m113.452169
  • Peer Reviewed
• [Presentation] 転写因子を起点とした変形性関節症のメカニズム (2016)
  • Author(s): 齋藤琢他
  • Organizer: 第29回日本軟骨代謝学会
  • Place of Presentation: 広島
  • Year and Date: 2016-02-19
  • Invited
• [Presentation] Notch/Rbpj/Hes1経路による変形性関節症の制御機構 (2015)
  • Author(s): 齋藤琢他
  • Organizer: 第33回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-23
  • Invited
• [Presentation] 変形性関節症の分子メカニズム (2015)
  • Author(s): 齋藤琢他
  • Organizer: 第15回日本抗加齢医学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2015-05-30
  • Invited
• [Presentation] Establishment of Surgical Destabilization Model of Mouse Ankle Osteoarthritis. (2015)
  • Author(s): Chang SH, Saito T, et al.
  • Organizer: Annual meeting of the Orthopaedic Research Society.
  • Place of Presentation: Las vegas, USA
  • Year and Date: 2015-03-28 – 2015-03-31
• [Presentation] Identification of Grem1 as a catabolic factor induced by mechanical stress loading in articular chondrocyte. (2014)
  • Author(s): Chang SH, Saito T, et al.
  • Organizer: Cold Spring Harbor Asia conferences.
  • Place of Presentation: Suzhou, China
  • Year and Date: 2014-11-05
• [Presentation] 変形性関節症への応用を目指した軟骨再生研究 (2014)
  • Author(s): 齋藤琢
  • Organizer: 第29回日本整形外科学会基礎学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-09
  • Invited
• [Presentation] HIF-1α IS ESSENTIAL FOR ARTICULAR CARTILAGE HOMEOSTASIS THROUGH INDUCTION OF ANABOLIC FACTORS AND SUPPRESSION OF CATABOLIC FACTORS. (2014)
  • Author(s): Okada K, Saito T, et al.
  • Organizer: Annual meeting of the American Society for bone and mineral research.
  • Place of Presentation: Houston
  • Year and Date: 2014-09-16
• [Presentation] Identification of Grem1 as a catabolic factor induced by mechanical stress loading in articular chondrocyte. (2014)
  • Author(s): Chang SH, Saito T, et al.
  • Organizer: Annual meeting of the American Society for bone and mineral research.
  • Place of Presentation: Houston
  • Year and Date: 2014-09-15
• [Presentation] HIFによる関節軟骨の変性メカニズム (2013)
  • Author(s): 3) 齋藤琢
  • Organizer: 日本整形外科学会基礎学術集会
  • Place of Presentation: 千葉
  • Invited
• [Remarks] 東京大学医学部付属病院 整形外科
  • URL: http://www.u-tokyo-ortho.jp/