Role of Runx2 in transdifferentiation from hypertrophic chondrocytes to osteoblasts

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K17087
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Morphological basic dentistry
• Research Institution: Nagasaki University
• Principal Investigator: SAKANE Chiharu 長崎大学, 先導生命科学研究支援センター, 助教 (40792578)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 軟骨細胞 / 骨芽細胞

Outline of Final Research Achievements

We generated Runx2 conditional knockout (cko) mice, in which Runx2 was specifically deleted in hypertrophic chondrocytes, by mating Runx2 flox mice with Col10a1 Cre transgenic mice. Vascular invasion into the cartilage was similarly observed in wild-type and Runx2 cko mice. We mated Col10a1 Cre transgenic mice with CAG-loxP-stop-loxP-LacZ reporter mice and confirmed that LacZ-positive hypertrophic chondrocytes transdifferentiate into osteoblasts. Although the deletion of Runx2 in hypertrophic chondrocytes interrupted the transdifferentiation of hypertrophic chondrocytes to osteoblasts, we did not observe the differences in the bone volume of trabecular and cortical bone between wild-type and Runx2 cko mice by micro-CT analysis.

Free Research Field

生物系、医歯薬学、歯学

Academic Significance and Societal Importance of the Research Achievements

軟骨内骨化では、軟骨細胞の成熟後、軟骨への血管侵入が必須である。Runx2 koマウスの軟骨への血管侵入は全く認めず、VEGFの発現が低下しており、Runx2 はVEGFを誘導し、軟骨への血管進入を制御すると考えられてきた。しかし、Runx2 ckoマウスでも、正常に軟骨への血管侵入は認められ、Runx2 の肥大軟骨細胞での発現は、軟骨への血管侵入に必須ではないことが明らかとなった。また、Runx2 の肥大軟骨細胞での欠損は、肥大軟骨細胞の骨芽細胞への分化転換を阻害したが、骨量に影響を及ぼさないことも明らかとなった。これらの発見は、軟骨内骨化の分子メカニズムの解明に貢献する。