Establishment of treatment strategy against osteoarthritis targeting transcription factor Nkx3.2

2015 Fiscal Year Final Research Report

• Project/Area Number: 26861189
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Osaka University
• Principal Investigator: Ebina Kosuke 大阪大学, 医学(系)研究科(研究院), 助教 (70612076)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 軟骨再生 / 滑膜細胞 / 変形性関節症 / 関節リウマチ / 同種移植 / 細胞バンク

Outline of Final Research Achievements

We confirmed that gene expression of Nkx3.2 is down-regulated in degenerated cartilage compared to intact cartilage of osteoarthritis patients. We developed scaffold-free tissue engineering construct (TEC) from synovial mesenchymal stem cells (SMSCs) which repairs cartilage defect. We also developed Nkx3.2 gene inserted plasmid, and transfected into synovial MSCs, which showed 90-30000 folds overexpression of Nkx3.2 gene and 2-7 folds of Sox9 gene. Finally, we induced chondrogenic differentiation to this Nkx3.2 gene overexpressed synovial MSCs, while failed to confirm significant increase in size and extra-cellular matrix production. Then, we tried to establish allogenic SMSCs bank to overcome the disadvantage of autogenic transplantation. We investigated that SMSCs from osteoarthritis and rheumatoid arthritis patients exhibit good potential to repair the osteochondral defects of nude rat, indicating the possibility of promising cell sources for cartilage repair.

Free Research Field

骨・軟骨代謝／関節リウマチ