Identification of candidate compounds for the maintenance of SFZ in the articular cartilage through Prg4 induction
Project/Area Number |
15K15536
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Orthopaedic surgery
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Research Institution | The University of Tokyo |
Principal Investigator |
Yano Fumiko 東京大学, 医学部附属病院, 特任講師 (80529040)
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Co-Investigator(Kenkyū-buntansha) |
小林 寛 東京大学, 医学部附属病院, その他 (20407951)
森崎 裕 東京大学, 医学部附属病院, 助教 (30508099)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
Keywords | 変形性膝関節症 / 関節軟骨最表層 / ルブリシン / 低分子化合物 |
Outline of Final Research Achievements |
The superficial zone (SFZ) of articular cartilage plays a cartilage-protective role by secretion of lubricin (Prg4). We separately isolated the SFZ cells and then treated with various agonists which are related to chondrogenic differentiation. When we analyzed treated SFZ cells by RT-PCR, Hif2a and Wnt signaling are candidate for upregulation of Prg4 expression and were performed by cDNA microarray. Since Hif2a significantly showed Prg4-promoter activity, to further know the mechanism of Prg4 regulation by Hif2a, we performed ChIP sequencing analysis using activated Hif2a in SFZ cells. In vivo analysis, we analyzed OA development of 4 types; Prg4-CreERT2; Hif2a flox (loss-of-function) or Hif2a Tg mice (activated Hif2a in Prg4 expressing cells), Prg4-CreERt2; βcatenin flox mice (loss-of-function) or Prg4-CreERt2; βcateninEx3 flox (activated βcatenin in Prg4 expressing cells).
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Regulation of Chondrocyte Survival in Mouse Articular Cartilage by p63.2017
Author(s)
Taniguchi Y, Kawata M, Chang SH, Mori D, Okada K, Kobayashi H, Sugita S, Hosaka Y, Inui H, Taketomi S, Yano F, Ikeda T, Akiyama H, Mills AA, Chung UI, Tanaka S, Kawaguchi H, and Saito T*
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Journal Title
Arthritis Rheumatol.
Volume: 69
Issue: 3
Pages: 598-609
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Impact of geriatric factors on surgical and prognostic outcomes in elderly patients with soft-tissue sarcoma.2017
Author(s)
Tsuda Y, Ogura K, Kobayashi E, Hiruma T, Iwata S, Asano N, Kawai A, Chuman H, Ishii T, Morioka H, Kobayashi H, Kawano H.
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Journal Title
Jpn J Clin Oncol
Volume: 2017/2/15
Issue: 5
Pages: 1-8
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes.2016
Author(s)
Kobayashi H, Chang S, Mori D, Itoh S, Hirata M, Hosaka Y, Taniguchi Y, Okada K, Mori Y, Yano F, Chung U, Akiyama H, Kawaguchi H, Tanaka S, Saito T.
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Journal Title
Nat Commun
Volume: 7
Issue: 1
Pages: 13336-13336
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability2016
Author(s)
Chang SH, Yasui T, Taketomi S, Matsumoto T, Kim-Kaneyama JR, Omiya T, Hosaka Y, Inui H, Omata Y, Yamagami R, Mori D, Yano F, Chung U, Tanaka S, Saito T.
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Journal Title
Osteoarthritis Cartilage
Volume: 24
Issue: 4
Pages: 688-697
DOI
Related Report
Peer Reviewed
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[Journal Article] Prevalence of hand osteoarthritis and its relationship to hand pain and grip strength in Japan: The third survey of the ROAD study.2016
Author(s)
Kodama R, Muraki S, Oka H, Iidaka T, Teraguchi M, Kagotani R, Asai Y, Yoshida M, Morizaki Y, Tanaka S, Kawaguchi H, Nakamura K, Akune T, Yoshimura N
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Journal Title
Mod Rheumatol.
Volume: 16
Pages: 1-7
Related Report
Peer Reviewed
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[Journal Article] <b>Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem </b><b>cells </b>2015
Author(s)
Saito T, Yano F, Mori D, Kawata M, Hoshi K, Takato T, Masaki H, Otsu M, Eto K, Nakauchi H, Chung UI, Tanaka S
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Journal Title
Biomedical Research
Volume: 36
Issue: 3
Pages: 179-186
DOI
NAID
ISSN
0388-6107, 1880-313X
Related Report
Peer Reviewed / Open Access
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