Functional analysis of a novel soluble FGF receptor from bone and cartilage and application to osteochondral regeneration

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11804
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Hiroshima University
• Principal Investigator: Kagawa Kazuko 広島大学, 病院(歯), 歯科診療医 (60432671)
• Co-Investigator(Kenkyū-buntansha): 津賀 一弘 広島大学, 医系科学研究科(歯), 教授 (60217289) ; 吉子 裕二 広島大学, 医系科学研究科(歯), 教授 (20263709)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 骨・軟骨再生 / 線維芽細胞増殖因子

Outline of Final Research Achievements

We studied a novel soluble FGF receptor (soluble FGFR2-IIIb) to obtain fundamental knowledge that can be applied to bone and cartilage regeneration.
The soluble FGFR2-IIIb that lacks the transmembrane and tyrosine kinase domains was expressed in calvaria, condylar cartilage, and cartilage of limb long bones in mice. The chondroprogenitor cell line ATDC5 and the preosteoblast cell line MC3T3-E1 did not express conventional FGFR2-IIIb, but only soluble FGFR2-IIIb.
The ATDC5 cells overexpressing soluble FGFR2-IIIb showed higher proliferative ability than control cells, and the addition of FGF10 further promoted proliferation. Furthermore, overexpression of soluble FGFR2-IIIb enhanced the activation of the MAPK/ERK signaling pathway by the addition of FGF10.

Free Research Field

歯学

Academic Significance and Societal Importance of the Research Achievements

骨・軟骨疾患は，歯科関連疾患の大きな割合を占める．骨再生療法や骨移植が歯科でも行われているが，適応の制限，不十分な予知性等の問題があり，より安全で侵襲の少ない再生療法の開発が希求される．
線維芽細胞増殖因子（FGF）やFGF 受容体（FGFR）は細胞の増殖分化や生存，移動に関与することが知られている．FGF2を用いた歯周組織再生材が実用化されており，これはFGF-FGFRシグナルが骨軟骨再生に密接に関連していることを示す．
本研究で得られた，新規可溶型FGFR2-IIIbの骨・軟骨細胞への影響やそのシグナル伝達に関する基礎的知見は，今後，より有効な骨・軟骨再生療法の開発へ繋がる可能性をもつ．