Hyaluronan degradation by HYAL2 is essential for odontoblastic differentiation and migration of mouse dental papilla cells

IF 4.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Haiyan Huang , Xiaoyu Hu , Jiayan Wu , Chenyu Song , Zhixin Tian , Beizhan Jiang
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Abstract

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 Hyal2 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.

HYAL2降解透明质酸对小鼠牙乳头细胞的牙骨质分化和迁移至关重要。
间充质祖细胞的牙本质分化和定向细胞迁移之间的协调对于牙本质的正常形成十分必要。细胞外基质中透明质酸(HA)的合成和降解创造了一个可直接调节细胞行为的有利环境。然而,HA 降解在牙本质形成过程中的作用和机制仍然未知。在这项研究中,我们发现 HA 消化促进了小鼠牙乳头细胞(mDPCs)的牙本质分化和细胞迁移。透明质酸酶 2(HYAL2)通过降解 HA 促进牙本质分化,而透明质酸酶 1(HYAL1)的作用微乎其微。沉默 Hyal2 会产生富含 HA 的细胞外环境,从而减少 F-肌动蛋白和丝状基质的形成,进而抑制 mDPCs 的细胞迁移。此外,激活 PI3K/Akt 信号可显著缓解 HA 积累对细胞分化的影响。综上所述,研究结果证实了HYAL2在牙本质形成过程中对HA降解的贡献,并揭示了HYAL2介导的HA降解调节mDPCs牙本质分化和迁移的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Matrix Biology
Matrix Biology 生物-生化与分子生物学
CiteScore
11.40
自引率
4.30%
发文量
77
审稿时长
45 days
期刊介绍: Matrix Biology (established in 1980 as Collagen and Related Research) is a cutting-edge journal that is devoted to publishing the latest results in matrix biology research. We welcome articles that reside at the nexus of understanding the cellular and molecular pathophysiology of the extracellular matrix. Matrix Biology focusses on solving elusive questions, opening new avenues of thought and discovery, and challenging longstanding biological paradigms.
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