Micro RNAs could modulate the reprogramming of osteoarthritic chondrocytes.

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 細胞・組織 / 再プログラミング / マイクロRNA / 変形性関節症 / 軟骨細胞 / microRNA / 脱分化

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): Takamatsu, A., Ohkawara, B., Ito, M., Masuda, A., Sakai, T., Ishiguro, N. and Ohno, K.
  • Journal Title: PLOS ONE Volume: 9(3) Issue: 3 Pages: e92699-e92699
  • DOI: 10.1371/journal.pone.0092699
  • Peer Reviewed / Open Access
• [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) Issue: 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) Issue: 1 Pages: R28-R28
  • DOI: 10.1186/ar4164
  • NAID: 40020134052
  • 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
  • NAID: 120005227637
  • 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
  • NAID: 120005227637
  • Peer Reviewed
• [Journal Article] Role of S100A12 in the pathogenesis of osteoarthritis (2012)
  • Author(s): Motoshige Nakashima
  • Journal Title: Biochem Biophys Res Commun Volume: 422 Issue: 3 Pages: 508-514
  • DOI: 10.1016/j.bbrc.2012.05.036
  • 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)
• [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)
• [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
• [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
• [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
• [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)
• [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)
• [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）
• [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）
• [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）
• [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: 日本軟骨代謝学会
  • Place of Presentation: 千里ライフサイエンスホール（豊中市）
• [Presentation] MicroRNA-23b suppress MMP-13 expression via post-transcriptional silencing of both hypoxia inducible factor-2α and rund-related transcription factor 2 expression in osteoarthritic chondrocytes (2013)
  • Author(s): Ishizuka,S; Sakai, T; Hiraiwa, H; Hamada, T; Nakashima, M; Oda T; Takamatsu A; Yamashita S; Ishiguro, N
  • Organizer: 2012 Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: San Antonio（アメリカ）
• [Presentation] Drug screening for inhibition of Wnt/b-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: 2012 Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: San Antonio（アメリカ）
• [Presentation] Successful Phenotype Rescue of Monolayer-expanded Osteoarthritic Human Chondrocytes using Pellet Culture (2013)
  • Author(s): Yohei Ono,Tadahiro Sakai, Hedeki Hiraiwa, Takashi Hamada, Motoshige Nakashima, Shinya Ishizuka, Warren Knudson, Cheryl B. Knudson, Naoki Ishiguro
  • Organizer: 2013 Annual meeting of AAOS
  • Place of Presentation: シカゴ（アメリカ）
• [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)
• [Presentation] MicroRNA-125b Regulates the Expression of Aggrecanase-1 (ADAMTS4) in Human Osteoarthritic Chondrocytes (2012)
  • Author(s): Tetsuya Matsukawa, Tadahiro Sakai, Hideki Hiraiwa, Takashi Hamada, Takaaki Omachi, Motoshige Nakashima, Shinya Ishizuka, Tomoyuki Oda, Akira Takamatsu, Satoshi Yamashita, Naoki Ishiguro
  • Organizer: 10th World Congress of the International Cartilage Repair Society 2012
  • Place of Presentation: モントリオール（カナダ）
• [Presentation] S100A12タンパクによる変形性関節症の進行における影響 (2012)
  • Author(s): 中島基成、酒井忠博、平岩秀樹、濱田恭、石塚真哉、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（名古屋市熱田区）
• [Presentation] OA半月板におけるHypoxia-inducible factor-2α の高発現 (2012)
  • Author(s): 石塚真哉、酒井忠博、平岩秀樹、濱田恭、中島基成、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（名古屋市熱田区）
• [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、中島基成、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（名古屋市熱田区）
• [Presentation] Increased expression of Hypoxia-inducible factor-2α in osteoarthritic meniscus cells (2012)
  • Author(s): Ishizuka,S; Sakai, T; Hiraiwa, H; Hamada, T; Nakashima, M; Oda T; Takamatsu A; Yamashita S; Ishiguro, N
  • Organizer: 第40回日本関節病学会
  • Place of Presentation: 鹿児島市民文化ホール、鹿児島サンロイヤルホテル（鹿児島市）