| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Prg4 is a secreted factor which is expressed in surface layer of articular cartilage. Although Prg4 has been reported to enhance the joint lubrication and inhibit the progression of cartilage degradation, regulatory mechanisms of its transcription are largely unknown. In this study, we showed that transcription factor Irx3 upregulates Prg4 expression by forming the transcriptional complex with TGF-beta-mediated Smad3 and Nfatc2 which is reported to repress osteoarthritis. We also reported the relationship between Irx3 and Wnt/beta-catenin signaling which is a major regulator of Prg4 expression. Irx3 increased not only the expression of Wnt4 and Wnt co-receptor Lgr6 but the transcriptional activity of Wnt signaling. These results indicate that Irx3 upregulates Prg4 expression by the interaction with TGF-beta or Wnt/beta-catenin signaling. Thus, Irx3 might be one of the clinical target for the treatment of cartilage degradation.
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