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Secreted Frizzled-Related Protein 1は歯髄細胞の象牙芽細胞様分化および修復象牙質形成を促進する

一法師, 啓太 IPPOSHI, Keita イッポウシ, ケイタ 九州大学

2022.03.23

概要

直接覆髄処置は、象牙芽細胞様細胞による修復象牙質の形成を介して、う蝕除去や歯の破折に伴う露髄から歯髄を保存するための治療法である。修復象牙質形成は、いくつかのシグナル伝達分子によって制御されるとされている。我々は、新生マウス臼歯歯胚の象牙芽細胞において強く発現することが報告されているSecreted frizzled-related protein(SFRP)1の、歯髄細胞の象牙芽細胞様分化と修復象牙質形成に及ぼす影響を検討した。

 ラット下顎切歯の組織切片において、Sfrp1の免疫組織化学染色を行った結果、歯髄、サービカルループ、内エナメル上皮細胞、エナメル芽細胞および前象牙芽細胞は、Sfrp1を弱く発現した。一方で、切端に近い象牙芽細胞層における成熟象牙芽細胞は、Sfrp1を強く発現した。同様にラット上顎臼歯の組織切片においても、象牙芽細胞がSfrp1を強く発現していた。ヒト歯髄細胞(hDPCs)は、歯根膜細胞および歯肉線維芽細胞と比較して、SFRP1を強く発現した。hDPCsを石灰化誘導培地で培養すると、象牙芽細胞関連遺伝子であるDSPP,DMP1,およびNESTINの発現が上昇し、さらにSFRP1の発現も増加した。SFRP1発現抑制を行ったhDPCsでは、発現抑制を行っていない細胞と比較し、石灰化物形成および象牙芽細胞関連遺伝子発現が有意に抑制され、骨関連遺伝子であるBMP-2の発現が有意に減少した。また、SFRP1タンパクを添加した石灰化誘導培地にて培養を行ったhDPCsでは、石灰化誘導培地にて培養を行ったものと比較し、石灰化物形成および象牙芽細胞関連遺伝子発現が有意に亢進し、BMP-2発現が有意に上昇した。ラット露髄モデルにSFRP1タンパクを応用すると、原生象牙質と同様の細管構造を持つ修復象牙質による、露髄面のほぼ完全な封鎖が認められた。

 以上の結果から、SFRP1はラット象牙芽細胞の成熟に関与しており、ヒト歯髄細胞の象牙芽細胞様分化およびラット修復象牙質形成を促進することが示唆された。

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