| Project/Area Number |
15KK0296
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Yano Fumiko 東京大学, 医学部附属病院, 特任准教授 (80529040)
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| Research Collaborator |
Warman Matthew L. Investigator, Howard Hughes Medical Institute Director, Orthopaedic Research Laboratories, Boston Children's Hospital Harriet M. Peabody Professor of Orthopaedic Surgery and Genetics, Harvard Medical School, Orthopaedic Research Laboratories, Professor
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| Project Period (FY) |
2016 – 2018
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
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| Keywords | ルブリシン / Runx1 / Prg4 / 変形性膝関節症 / 軟骨再生 |
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| Outline of Final Research Achievements |
To reveal the roles of Prg4 expressed cells as progenitor in developmental process, we observed how it cause defect in joint formation when Prg4+ cells are prevented from having progeny by DTA (Prg4-EGFP-CreERT2/+ ;R26DTA/+). To determine whether Prg4 expressing cells are required for articular cartilage formation during embryonic and/or early postnatal stage, these Prg4-EGFP-CreERT2/+ ;R26DTA/+ mice were injected by both of pre-and post-natal TM 6 times injection. When we analyzed The Prg4GFPCreERt2/+R26DTA /+mice at 2months or 6 months of the age that received tamoxifen (i.e., DTA ablated) showed fewer superficial chondrocytes, thinner cartilage and less subchondral bone compared to controls. Prg4-expressing cells located at the joint surface in the embryo serve as a progenitor population for all deeper layers of the mature articular cartilage.
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| Academic Significance and Societal Importance of the Research Achievements |
変形性関節症は軟骨の変性を主体とした退行性疾患であり、痛みや関節機能の低下を来して生活の質を著しく低下させる。Prg4は関節軟骨最表層や滑膜で高発現し、関節に潤滑性を与えるが、近年Prg4発現細胞には軟骨細胞のプロジェニターが含まれることが分かってきた。国際共同研究強化の支援を受けて共同研究先のハーバード大学医学部・ボストン子供病院、整形外科のProf. Warman研究室に所属し、胎生期から成体期における関節軟骨に発現するPrg4の研究を行った。組織学的解析だけでなく関節軟骨表層を3D共焦点顕微鏡で可視化して定量的に解析することで、関節軟骨におけるPrg4発現細胞の役割を明らかにした。
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