Project/Area Number |
24659672
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
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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 *help |
¥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.
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