PTH/PTHrP receptor signaling in chondrocyte

2015 Fiscal Year Final Research Report

• Project/Area Number: 24790291
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Aichi Gakuin University
• Principal Investigator: Hirai Takao 愛知学院大学, 歯学部, 講師 (80389072)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: PTH/PTHrP受容体 / circadian clock

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.

Free Research Field

生体分子