| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Outline of Final Research Achievements |
Parathyroid hormone-related protein (PTHrP) and Indian hedgehog (Ihh) form a negative feedback loop that controls the differentiation of chondrocytes in the fetal growth plate. Actions of PTHrP are mediated through the parathyroid hormone (PTH)/PTHrP receptor (PPR). Recent studies indicated that Gsa is the major mediator of the anti-differentiation action of the PPR, while activation of both Gsa and Gq/11a is required for quiescence of stem-like chondrocytes in the resting zone of the growth plate. These studies showed that the stimulation of PTHrP increased the transcriptional factor Nfil3/E4BP4 in articular chondrocytes. On a molecular level, both loss-of-function and gain-of-function experiments demonstrated that Nfil3/E4BP4 negatively regulated Bmp4 and Ptgs2 expression. Our results indicated that PPR signaling in chondrocytes regulated clock gene Nfil3/E4BP4 and may contribute to circadian clock in articular cartilage.
|
