Exploring the anchoring molecules and cleaving enzymes of Chondromodulin-I, a cartilage-derived angiogenesis inhibitor

• Project/Area Number: 15K01800
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Kyoto University
• Principal Investigator: Hiraki Yuji 京都大学, ウイルス・再生医科学研究所, 教授 (40144498)
• Co-Investigator(Kenkyū-buntansha): 三浦 重徳 京都大学, ウイルス・再生医科学研究所, 助教 (70511244)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: コンドロモジュリン-I / 血管新生抑制因子 / 軟骨 / 細胞外マトリックス / アンカー分子 / 切断酵素 / Chondromoduin-I / 軟骨マトリックス / コンドロモジュリン / エンドプロテアーゼ

Outline of Final Research Achievements

In the present study, we isolated the ChM-I-associating extracellular matrix (ECM) protein complexes by immunoprecipitation of ChM-I from the rib cartilage extracts prepared under the mild dissociating condition. By the mass spectrometric analyses, we obtained several kinds of candidate molecules interacting with ChM-I and found one of them showed direct protein interaction with ChM-I in immunoprecipitation analyses. As for ChM-I-cleaving enzyme, we demonstrated that the cleavage activity is localized to the cell surface or cartilage ECM irrespective of differentiation states of cartilage cells. These results help us to understand the molecular mechanism underlying establishment and removal of anti-angiogenic barrier during the cartilage development.