Development of a new drug for treating osteoarthritis caused by increased expression of Dkk1 molecule

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15661
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya University
• Principal Investigator: Ishiguro Naoki 名古屋大学, 医学系研究科, 教授 (20212871)
• Co-Investigator(Kenkyū-buntansha): 酒井 忠博 名古屋大学, 医学系研究科, 准教授 (60378198) ; 平岩 秀樹 名古屋大学, 医学部附属病院, 病院講師 (70566976) ; 高橋 伸典 名古屋大学, 医学部附属病院, 病院講師 (20570196)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: Dkk1 / Wnt signal / β - catenin

Outline of Final Research Achievements

We could not find a compound with an enhancing effect on Dkk1 expression. As a cause, we considered the possibility that β - catenin mutation induces the increasing of Wnt signal. Dkk1 is a target gene of Wnt signal, and Dkk1 production is enhanced in cells that are enhanced. Considering the possibility that the enhancing action of the drug is difficult to detect in such Dkk1 producing cells, two kinds of compounds were obtained by changing the cells. These drugs were able to confirm Dkk1 expression enhancing action even at the level of mRNA. However, in the luciferase assay by TOP flash, the Wnt signal activity increased and the opposite result was obtained. The goal of the research was changed to a new development of a drug having a Dkk1 expression lowering action. At present, one kind of drug is selected to confirm the reduction of Dkk1 expression at the mRNA level and the activity of decreasing the activity of Wnt signal. We are continuing the examination.

Free Research Field

整形外科学