Investigation of molecular and mechanosensitive mechanisms on lubricin-targeted gene expression specific to the surface of joint

• Project/Area Number: 24390352
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto University
• Principal Investigator: YAMAMOTO KOJI 京都大学, 健康長寿社会の総合医療開発ユニット, 特定准教授 (70536565)
• Co-Investigator(Kenkyū-buntansha): AKIYAMA Haruhiko 岐阜大学, 医学部, 教授 (60402830) ; TSUMAKI Noriyuki 京都大学, iPS細胞研究所, 教授 (50303938)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2012: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: ルブリシン / Prg4 / 変形性関節症 / メカノセンシング / 関節表層遺伝子 / 遺伝子改変マウス / PRG4 / メカニカルストレス / 関節表層 / マイクロアレイ / 潤滑機能 / 関節軟骨

Outline of Final Research Achievements

In vivo observation of Prg4, which encodes lubricin, using Prg4-RFP-Tg mice with the experimental osteoarthritis model showed that the expression of RFP on the cartilage surface was attenuated immediately after surgical operation. In addition, by using articular chondrocytes derived from Prg4-RFP-Tg;Sox9-EGFP mice, joint surface-specific gene expression profile was constructed through FACS and DNA microarray analyses. On the basis of these results, conditional gene deletion using Prg4-Cre mouse revealed an abnormal joint development. Furthermore, we identified a candidate region in the Prg4 promoter sequence associated with Prg4 expression and investigated molecular and mechanosensitive mechanisms on lubricin-targeted gene expression.