The coordination between odontoblastic differentiation and directed cell migration of mesenchymal progenitors is necessary for regular dentin formation. The synthesis and degradation of hyaluronan (HA) in the extracellular matrix create a permissive niche that directly regulates cell behaviors. However, the role and mechanisms of HA degradation in dentin formation remain unknown. In this work, we present that HA digestion promotes odontoblastic differentiation and cell migration of mouse dental papilla cells (mDPCs). Hyaluronidase 2 (HYAL2) is responsible for promoting odontoblastic differentiation through degrading HA, while hyaluronidase 1 (HYAL1) exhibits negligible effect. Silencing generates an extracellular environment rich in HA, which attenuates F-actin and filopodium formation and in turn inhibits cell migration of mDPCs. In addition, activating PI3K/Akt signaling significantly rescues the effects of HA accumulation on cytodifferentiation. Taken together, the results confirm the contribution of HYAL2 to HA degradation in dentinogenesis and uncover the mechanism of the HYAL2-mediated HA degradation in regulating the odontoblastic differentiation and migration of mDPCs.

中文翻译：

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HYAL2 降解透明质酸对于小鼠牙乳头细胞的成牙本质细胞分化和迁移至关重要

成牙本质细胞分化和间充质祖细胞定向细胞迁移之间的协调对于正常的牙本质形成是必要的。细胞外基质中透明质酸 (HA) 的合成和降解创造了一个直接调节细胞行为的许可生态位。然而，HA 降解在牙本质形成中的作用和机制仍不清楚。在这项工作中，我们提出HA消化促进小鼠牙乳头细胞（mDPC）的成牙本质细胞分化和细胞迁移。透明质酸酶 2 (HYAL2) 负责通过降解 HA 促进成牙本质细胞分化，而透明质酸酶 1 (HYAL1) 的作用可以忽略不计。沉默会产生富含 HA 的细胞外环境，从而减弱 F-肌动蛋白和丝状伪足的形成，进而抑制 mDPC 的细胞迁移。此外，激活 PI3K/Akt 信号传导可显着挽救 HA 积累对细胞分化的影响。综上所述，结果证实了 HYAL2 对牙本质发生中 HA 降解的贡献，并揭示了 HYAL2 介导的 HA 降解调节 mDPC 成牙本质细胞分化和迁移的机制。