a new disease-modifying osteoarthritis drug (DMOAD) candidate using a cell based screening system

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659665
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: YANO Fumiko 東京大学, 医学部附属病院, 助教 (80529040)
• Co-Investigator(Kenkyū-buntansha): MORIZAKI Yutaka 東京大学, 医学部附属病院, 助教 (30508099)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 変形性膝関節症 / 軟骨再生

Outline of Final Research Achievements

To identify a new disease-modifying osteoarthritis drug (DMOAD) candidate, we screened 2500 synthetic small compounds for chondrogenic agents via four steps using the Col2GFP-ATDC5 system and identified a small thienoindazole derivative compound, TD-198946, as a　novel DMOAD candidate. We tested its efficacy as a DMOAD via intra-articular injections directly into the joint space in a mouse model of OA both at the onset (prevention model) and 4 weeks after (repair model). We further investigated the mechanism of the drug action and its molecular target using in vitro (DNA microarray analysis and Proteomic analysis) and in vivo assays. TD-198946 strongly induced chondrogenic differentiation without promoting hypertrophy and successfully prevented and repaired degeneration of the mouse articular cartilage. TD-198946 exerted its effect through the regulation of Runx1 expression.

Free Research Field

軟骨代謝学