Identification of candidate compounds for the maintenance of SFZ in the articular cartilage through Prg4 induction

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K15536
• 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, 特任講師 (80529040)
• Co-Investigator(Kenkyū-buntansha): 小林 寛 東京大学, 医学部附属病院, その他 (20407951) ; 森崎 裕 東京大学, 医学部附属病院, 助教 (30508099)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 変形性膝関節症 / 関節軟骨最表層

Outline of Final Research Achievements

The superficial zone (SFZ) of articular cartilage plays a cartilage-protective role by secretion of lubricin (Prg4). We separately isolated the SFZ cells and then treated with various agonists which are related to chondrogenic differentiation. When we analyzed treated SFZ cells by RT-PCR, Hif2a and Wnt signaling are candidate for upregulation of Prg4 expression and were performed by cDNA microarray. Since Hif2a significantly showed Prg4-promoter activity, to further know the mechanism of Prg4 regulation by Hif2a, we performed ChIP sequencing analysis using activated Hif2a in SFZ cells. In vivo analysis, we analyzed OA development of 4 types; Prg4-CreERT2; Hif2a flox (loss-of-function) or Hif2a Tg mice (activated Hif2a in Prg4 expressing cells), Prg4-CreERt2; βcatenin flox mice (loss-of-function) or Prg4-CreERt2; βcateninEx3 flox (activated βcatenin in Prg4 expressing cells).

Free Research Field

軟骨代謝