Elucidation of growth and differentiation control mechanism of chondrocytes by activation of Src family molecule Hck

Research Project

Project/Area Number	18K17017
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 57010:Oral biological science-related
Research Institution	Nagasaki University
Principal Investigator	MATSUURA Keiko 長崎大学, 医歯薬学総合研究科(歯学系), 特任研究員 (20770423)
Project Period (FY)	2018-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords	Hck / Runx2 / 軟骨増植 / Wnt / hedgehog / 間葉系細胞 / 軟骨細胞の増殖・分化 / 軟骨細胞
Outline of Final Research Achievements	Runx2 is required for chondrocyte proliferation and maturation. In our laboratory, we introduced Runx2 into early cultured chondrocytes derived from Runx2 knockout (ko) mice, searched for the target gene of Runx2, and identified hematopoietic cell kinase Hck as one of the induced genes. On the other hand, although it is known that there is a partial functional overlap between the Src kinase family, Hck is specifically expressed in the cartilaginous limb skeleton. To understand this selective gene expression and its physiological significance, it is necessary to clarify the molecular background of the correlation between chondrocyte proliferation and differentiation. In this study, we analyzed the involvement of Hck in the proliferation and differentiation of chondrocytes using the Hck knockdown system.
Academic Significance and Societal Importance of the Research Achievements	軟骨肉腫の病因および変形性関節症の骨棘形成におけるRunx2の標的遺伝子の関与を解明する必要である。本研究の成果により、Hckは軟骨性骨格、特に胎児の四肢骨格で高度に発現し、その発現はRunx2によって制御されていることを強く示唆している。未熟な軟骨細胞におけるSpp1の発現は、Hckを介した炎症性シグナル伝達の活性化によって引き起こされた可能性が高い。Runx2は変形性関節症の病因に関与しており、機械的損傷によって誘発される炎症プロセスは心的外傷後変形性関節症の発症につながるため、Hckは変形性関節症の発症、特に骨棘形成にも関与している可能性を示唆した。