Micro RNAs could modulate the reprogramming of osteoarthritic chondrocytes.

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659672
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya University
• Principal Investigator: SAKAI TADAHIRO 名古屋大学, 医学部附属病院, 病院講師 (60378198)
• Co-Investigator(Kenkyū-buntansha): HIRAIWA Hideki 名古屋大学, 医学部附属病院, 病院助教 (70566976) ; HAMADA Takashi 名古屋大学, 医学系研究科, 寄附講座助教 (90566978) ; OHMACHI Takaaki 名古屋大学, 医学部附属病院, 医員
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 細胞・組織 / 再プログラミング / マイクロRNA

Research Abstract

The pathological roles of microRNAs in reprogramming of chondrocytes were analysed. First, we demonstrated that miR-125b plays a role in regulating the expression of ADAMTS4 in human chondrocytes. The mean fluorescence intensity (MFI) ratio of CD54 to CD44 could be an adequate candidate as the index of the differentiation status of chondrocytes. Chondrogenic induction in three-dimensional pellet culture successfully rescued the expression of chondrocyte phenotype marker genes to native levels. We compared the muitipotency of bone-marrow-derived mesenchymal stem cells (MSCs) with osteoarthritic chondrocyte(OAC)s. OACs differentiated into adipogenic, osteogenic, and chondrogenic lineages same as MSCs. The expressions of microRNAs related to chondrocytes decreased in de-diffrentiation and recovered during re-differentiation. Finally, we found that intraarticular injection of verapamil inhibited OA progression as well as nuclear localizations of beta-catenin in a rat OA model.

Research Products

• [Journal Article] Verapamil protects against cartilage degradation in osteoarthritis by inhibiting Wnt/β-catenin signaling (2014)
  • Author(s): Akira Takamatsu, Bisei Ohkawara, Mikako Ito, Akio Masuda, Tadahiro Sakai, Naoki Ishiguro, Kinji Ohno
  • Journal Title: Plos One Volume: 9(3) Pages: e92699
  • DOI: 10.1371/journal.pone.0092699
  • Peer Reviewed
• [Journal Article] Chondrogenic capacity and alterations in hyaluronan synthesis of cultured human osteoarthritic chondrocytes (2013)
  • Author(s): Ono Y, Sakai T, Hiraiwa H, Hamada T, Omachi T, Nakashima M, Ishizuka S, Matsukawa T, Knudson W, Knudson CB, Ishiguro N
  • Journal Title: Biochem Biophys Res Commun Volume: 435(4) Pages: 733-739
  • DOI: 10.1016/j.bbrc.2013.05.052
  • Peer Reviewed
• [Journal Article] MicroRNA-125b regulates the expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes (2013)
  • Author(s): Matsukawa T, Sakai T, Yonezawa T, Hiraiwa H, Hamada T, Nakashima M, Ono Y, Ishizuka S, Nakahara H, Lotz MK, Asahara H, Ishiguro N
  • Journal Title: Arthritis Res Ther Volume: 15(1) Pages: R28
  • DOI: 10.1186/ar4164
  • Peer Reviewed
• [Journal Article] SURFACE MARKERS AND GENE EXPRESSION TO CHARACTERIZE THE DIFFERENTIATION OF MONOLAYER EXPANDED HUMAN ARTICULAR CHONDROCYTES (2013)
  • Author(s): TAKASHI HAMADA, TADAHIRO SAKAI, HIDEKI HIRAIWA, MOTOSHIGE NAKASHIMA, YOHEI ONO, HIROHITO MITSUYAMA and NAOKI ISHIGURO
  • Journal Title: Nagoya J. Med. Sci Volume: 75 Pages: 101-111
  • Peer Reviewed
• [Presentation] 変形性関節症由来軟骨細胞の再分化能についての検討 (2013)
  • Author(s): 小田智之、酒井忠博、平岩秀樹、濱田恭、大野洋平、中島基成、石塚真哉、高松晃、山下暁士、石黒直樹
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 幕張メッセ(千葉市)
  • Year and Date: 20131017-18
• [Presentation] Wntシグナル経路の制御を介した変形性関節症に対する新たな治療薬の検索 (2013)
  • Author(s): 高松晃、酒井忠博、平岩秀樹、濱田恭、中島基成、松川哲也、小田智之、山下暁士、宮本健太郎、石黒直樹、大河原美静、大野欽司
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 幕張メッセ(千葉市)
  • Year and Date: 20131017-18
• [Presentation] Drug screening for treating osteroarthritis through regulation of Wnt/β-catenin signaling (2013)
  • Author(s): Akira Takamatsu, Bisei Ohkawara, Tadahiro Sakai, Kinji Ohno, Naoki Ishiguro
  • Organizer: The Osteoarthritis Research Society International
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20130418-21
• [Presentation] Wntシグナル経路の制御を介した変形性関節症に対する新たな治療薬の検索 (2013)
  • Author(s): 高松晃、大河原美静、酒井忠博、大野欽司、石黒直樹
  • Organizer: 第26回日本軟骨代謝学会
  • Place of Presentation: 千里ライフサイエンスセンター(豊中市)
  • Year and Date: 20130301-02
• [Presentation] 変形性関節症由来軟骨細胞(OAC)の再分化能についての検討 (2013)
  • Author(s): 小田智之、酒井忠博、平岩秀樹、濱田恭、大野洋平、中島基成、石塚真哉、高松晃、山下暁士、石黒直樹
  • Organizer: 第26回日本軟骨代謝学会
  • Place of Presentation: 千里ライフサイエンスセンター(豊中市)
  • Year and Date: 20130301-02
• [Presentation] MicroRNA-23b suppress MMP-13 expression via post-transcriptional silencing of both hypoxia inducible factor-2αand rund-related transcription factor 2 expression in osteoarthritic chondrocytes (2013)
  • Author(s): Shinya Ishizuka, Tadahiro Sakai, Hideki Hiraiwa, Takashi Hamada, Motoshige Nakashima, Tomoyuki Oda, Satoshi Yamashita, Akira Takamatsu, Naoki Ishiguro
  • Organizer: Orthopaedic Research Society
  • Place of Presentation: San Antonio, USA
  • Year and Date: 20130126-29
• [Presentation] Drug screening for inhibition of Wnt/β-catenin signaling in osteoarthritis (2013)
  • Author(s): Akira Takamatsu, Bisei Ohkawara, Tadahiro Sakai, Hideki Hiraiwa, Takashi Hamada, Motoshige Nakashima, Shinya Ishizuka, Tomoyuki Oda, Satoshi Yamashita, Kinji Ohno, Naoki Ishiguro
  • Organizer: Orthopaedic Research Society
  • Place of Presentation: San Antonio, USA
  • Year and Date: 20130126-29
• [Presentation] microRNA-23bはHIF2-α、RUNX2の発現抑制を介してOA軟骨細胞におけるMMP-13の発現を制御する (2012)
  • Author(s): 石塚真哉、酒井忠博、平岩秀樹、濱田恭、中島基茂、小田智之、高松晃、山下暁士、石黒直樹
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 20121005-06