Ogg1 protects against the catabolic stress-induced downregulation of chondrocyte activity and the apoptosis in OA.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592236
• 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: YUDOH Kazuo 聖マリアンナ医科大学, 医学(系)研究科(研究院), 教授 (60272928)
• Co-Investigator(Kenkyū-buntansha): KARASAWA Rie 聖マリアンナ医科大学, 医学(系)研究科 (研究院), 講師 (50434410)
• Project Period (FY): 2011 – 2013
• Keywords: 変形性関節症 / 核酸損傷 / 酸化ストレス

Research Abstract

It is well known that chondrocytes produce excess amounts of reactive oxygen species (ROS) as well as proinflammatory cytokines and chemokines in response to mechanical and chemical stresses. An oxidized form of guanine, 8-oxo-7,8-dihydroxyguanine (8-oxoguanine), is a major causative lesion for mutagenesis by ROS, because it can cause a stable base pair with adenine or cytosine during DNA replication. 8-Oxoguanine DNA glycosylase (Ogg1) repairs 8-oxoguanine, one of the most abundant DNA adducts caused by oxygen free radicals. We demonstrated that depletion of cellular antioxidant, Ogg1, in osteoarthritic chondrocytes participates in the degeneration of articular cartilage in OA. Our findings suggest that Ogg1 may have a potential to protect against the catabolic factor-induced down-regulation of chondrocyte activity and apoptosis in OA.

Research Products

• [Journal Article] Serum level of soluble triggering receptor expressed on myeloid cells-1 as a biomarker of disease activity in relapsing polychondritis (2014)
  • Author(s): Sato T, Yamano Y, Tomaru U, Shimizu Y, Ando H, Okazaki T, Nagafuchi H, Shimizu J, Ozaki S, Miyazawa T, Yudoh K, Oka H, Suzuki N
  • Journal Title: Modern Rheumatol Volume: 24(1) Pages: 126-136
  • Peer Reviewed
• [Journal Article] Layilin, a talin-binding hyaluronan receptor, is expressed in human articular chondrocytes and synoviocytes and is down-regulated by interleukin-1β (2013)
  • Author(s): Murata M, Yudoh K, Shimizu H, Beppu M, Nakamura H, Kato T, Masuko K
  • Journal Title: Modern Rhematology Volume: 23(3) Pages: 478-88
  • Peer Reviewed
• [Journal Article] Positive feedback loop via astrocytes causes chronic inflammation in virus-associated myelopathy (2013)
  • Author(s): Ando H., Sato T., Tomaru U., Yoshida M., Utsunomiya A., Yamauchi J., Araya N., Yagishita N., Coler-Reilly A., Shimizu Y., Yudoh K., Hasegawa Y., Nishioka K., Nakajima T., Jacobson S., Yamano Y.
  • Journal Title: Brain Volume: 136 Pages: 2876-87
  • Peer Reviewed
• [Journal Article] Protein profiles of peripheral blood mononuclear cells as a candidate biomarker for Behçet's disease (2013)
  • Author(s): Yoshioka T, Kurokawa MS, Sato T, Nagai K, Iizuka N, Arito M, Takakuwa Y, Nakano H, Ooka S, Suematsu N, Okamoto K, Yudoh K, Nakamura H, Suzuki N, Ozaki S, Kato T
  • Journal Title: Clin Exp Rheumatol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Presentation] Mitochondrial DNA repair enzyme Ogg1 is essential for protection against the downregulation of chondrocyte activity in OA (2013)
  • Author(s): Yudoh K
  • Organizer: The 2013 World Congress on Osteoarthritis
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20130418-21
• [Presentation] Impairment of Mitochodrial 8-oxoguanine DNA glycosylase (Ogg1) against of accumulation of oxidative stress (2012)
  • Author(s): Yudoh K
  • Organizer: The 2012 World Congress on Osteoarthritis
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20120426-29
• [Presentation] 8-oxoguanine DNA glycosylase activity in OA (2011)
  • Author(s): Yudoh K
  • Organizer: EULAR 2012
  • Place of Presentation: London, UK
  • Year and Date: 20110525-28