Role of chondrocyte DNA repair enzymes in the degeneration of articular cartilage in osteoarthritis.

• Project/Area Number: 26462323
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: YUDO KAZUO 聖マリアンナ医科大学, 医学研究科, 教授 (60272928)
• Co-Investigator(Kenkyū-buntansha): 油井 直子 聖マリアンナ医科大学, 医学部, 講師 (20266696) ; 唐澤 里江 聖マリアンナ医科大学, 医学研究科, 講師 (50434410)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 変形性関節症 / 軟骨細胞 / 核酸修復酵素 / 核酸損傷修復酵素 / 軟骨変性 / メカニカルストレス / 酸化ストレス / 細胞エネルギー代謝 / ATPエネルギー / DNA修復酵素 / 活性酸素種

Outline of Final Research Achievements

Aging is one of the major pathologic factors associated with osteoarthritis (OA). It has been indicated that the NAD-dependent deacetylase sirtuin-1 (Sirt-1) has an important role in human aging.It has been suggested that Sirt-1 promotes osteogenic and chondrogenic differentiation of mesenchymal stem cells.
We postulated that Sirt-1 regulates a hypertrophic chondrocyte lineage and osteophyte formation through the activation of osteogenic transcription factor Runx2 in osteoarthritic chondrocytes.Our findings suggest that the NAD-dependent deacetylase Sirt-1 may upregulate the osteophyte formation and the expression of cartilage degrading enzyme MMP-13 through the mechanism involving the acceleration of the osteogenic transcription factor Runx2 in OA cartilage tissues.

Research Products

• [Journal Article] The NAD-Dependent deacetylase sirtuin-1 regulates the expression of osteogenic transcriptional activator runt-related transcription factor 2 (Runx2) and production of matrix metalloproteinase (MMP)-13 in chondrocytes in osteoarthritis. (2016)
  • Author(s): Terauchi K, Kobayashi H, Yatabe K, Yui N, Fujiya H, Niki H, Musha H, Yudoh K (Corresponding author).
  • Journal Title: Int. J Molecular Science. Volume: 1019 Pages: 1033-1033
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Polyhydroxylated C60 fullerenes prevent chondrocyte catabolic activity at the concentration of nanomolar order in osteoarthritis. (2016)
  • Author(s): Yoshioka H, Yui N, Fujiya H, Musha H, Niki H, Karasawa R, Yudoh K (Corresponding author).
  • Journal Title: International Journal of Clinical Rheumatology Volume: 11(5) Pages: 70-76
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mechanical stress and oxidative stress in osteoarthritis. (2016)
  • Author(s): Naoko Yui, Haruki Musha, Kazuo Yudoh
  • Journal Title: Journal of Physical Fitness and Sports Medicine Volume: 5 Pages: 81-86
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Age-related Decrease of Sirtuin 2 Protein in Human Peripheral Blood Mononuclear Cells, 8(3): 256 - 258 (2015)
  • Author(s): Kazuo Yudoh, Rie Karasawa, Junji Ishikawa
  • Journal Title: Current Aging Science Volume: 8 Pages: 256-258
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Age-related decrease of sirtuin 2 protein in human peripheral blood mononuclear cells. (2015)
  • Author(s): Yudoh K, Karasawa R, Ishikawa J.
  • Journal Title: Curr Aging Sci. Volume: 1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The DNA Repair Enzyme Apurinic/Apyrimidinic Endonuclease (Apex Nuclease) 2 Has the Potential to Protect against Down-Regulation of Chondrocyte Activity in Osteoarthritis (2014)
  • Author(s): 油井直子
  • Journal Title: International Journal of Molecular Sciences Volume: 15 Issue: 9 Pages: 14921-14934
  • DOI: 10.3390/ijms150914921
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Water-Soluble C60-(OH)24 Fullerene Hydroxide Protects against the Catabolic Stress-Induce Downregulation of Chondrocyte Activity in Osteoarthritis. (2014)
  • Author(s): Yoshioka H, Yui N, Fujiya H, Musha H, Beppu M, Karasawa R, Yudoh K.
  • Journal Title: J Nanotech Smart Mater Volume: １（４０１） Pages: 1-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] NAD依存性脱アセチル化酵素Sirtuin1と骨形成転写因子Runx2の変性軟骨細胞における役割 (2016)
  • Author(s): 寺内昂, 遊道和雄, 小林創, 油井直子, 藤谷博人, 仁木久照, 武者春樹.
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡県福岡市福岡国際会議場
  • Year and Date: 2016-10-13
• [Presentation] 変形性関節症の軟骨細胞におけるエネルギー代謝とSirtuin1との関連について. (2016)
  • Author(s): 小林創, 油井直子, 寺内昂, 藤谷博人, 遊道和雄, 仁木久照, 武者春樹.
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡県福岡市福岡国際会議場
  • Year and Date: 2016-10-13
• [Presentation] The Role of ATP-Activeted Protein Kinase(AMPK) in the Chondrocyte Energy Balance and IL-β-induced Production of MMP-13 in Osteoarthritis(OA). (2016)
  • Author(s): Yui N, Musha H, Fujiya H, Yatabe K, Yoshioka H, Terauchi K, Yudoh K.
  • Organizer: OARSI 2016 World Congress
  • Place of Presentation: RAIコンベンションセンター アムステルダム（オランダ王国）
  • Year and Date: 2016-04-01
  • Int'l Joint Research
• [Presentation] Significance of defence mechanism for oxidative DNA damages in osteoarthritis: DNA repair enzyme, apurinic/apyrimidinic endonuclease (APEX"), protects against the catabolysis of articular cartilage in OA. (2015)
  • Author(s): Yui N, Musha H, Fujiya H, Yatabe K, Yoshioka H, Terauchi K, Yudoh K.
  • Organizer: 15th International Conference on ISANH Antioxidants
  • Place of Presentation: Paris, France
  • Year and Date: 2015-06-22
  • Int'l Joint Research
• [Presentation] Water-soluble C60－【OH)24 fullerene hydroxide as a therapeutic agent in the degeneration of articular cartilage in osteoarthritis. (2015)
  • Author(s): Yui N, Yoshioka H, Fujiya H, Musha H, Karasawa R, Yudoh K.
  • Organizer: World congress on Osteoarthritis 2015.
  • Place of Presentation: Seattle, USA.
  • Year and Date: 2015-04-30
  • Int'l Joint Research
• [Presentation] DNA OXIDATIVE DAMAGE AND ITS REPAIR ENZYME (OGG1) IN OSTEOARTHRITIC CHONDROCYTES. (2014)
  • Author(s): Yudoh K, Karasawa R.
  • Organizer: 2014 World Congress on Osteoarthritis.
  • Place of Presentation: Paris, France
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] DNA REPAIR ENZYME, APURINIC/APYRIMIDINIC ENDONUCLEASE 2 (APEX2), HAS A POTENTIAL TO PROTECT AGAINST THE DOWN-REGULATION OF CONDROCYTE ACTIVITY IN OSTEOARTHRITIS. (2014)
  • Author(s): Yui N, Yoshioka H, Karasawa R, Yudoh K.
  • Organizer: 2014 World Congress on Osteoarthritis.
  • Place of Presentation: Paris, France
  • Year and Date: 2014-04-24 – 2014-04-27
• [Book] 関節症(Osteoaarthritis:OA)治療法の今後の展開：OA治療を目的をとする自己注射薬の可能性について. 自己注射 (2016)
  • Author(s): 遊道和雄.
  • Publisher: ㈱技術情報協会
• [Book] 自己注射―変形性関節症(Osteoarthritis:OA)治療法の今後の展開：OA治療を目的とする自己注射薬の可能性について (2016)
  • Author(s): 遊道 和雄
  • Publisher: 技術情報協会
• [Remarks] 聖マリアンナ医科大学 難病治療研究センター 診断治療法開発 創薬部門
  • URL: http://nanchiken.jp/shindan/