4.7 Article

The Critical Role of MMP13 in Regulating Tooth Development and Reactionary Dentinogenesis Repair Through the Wnt Signaling Pathway

期刊

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.883266

关键词

collagenase; dentinogenesis; histone deacetylase; matrix metalloproteinase; odontoblast; Wnt signaling

资金

  1. National Institutes of Dental and Craniofacial Research (NIDCR) [R01-DE025885]
  2. NIH [S10 OD010751]
  3. European Molecular Biology Organization (EMBO) [ASTF 167-2016]

向作者/读者索取更多资源

Matrix-metalloproteinase-13 (MMP13) plays an important role in tooth development and mineralization processes. Knockout of MMP13 in mice resulted in altered dentin phenotype, reduced dentin volume, and decreased calcium deposition. The study also revealed an interaction between MMP13 and the Wnt-signaling pathway. These findings highlight the critical role of MMP13 in tooth development and mineralization.
Matrix-metalloproteinase-13 (MMP13) is important for bone formation and remodeling; however, its role in tooth development remains unknown. To investigate this, MMP13-knockout (Mmp13(-/-)) mice were used to analyze phenotypic changes in the dentin-pulp complex, mineralization-associated marker-expression, and mechanistic interactions. Immunohistochemistry demonstrated high MMP13-expression in pulp-tissue, ameloblasts, odontoblasts, and dentin in developing WT-molars, which reduced in adults, with human-DPC cultures demonstrating a >2000-fold increase in Mmp13-expression during mineralization. Morphologically, Mmp13(-/-) molars displayed critical alterations in the dentin-phenotype, affecting dentin-tubule regularity, the odontoblast-palisade and predentin-definition with significantly reduced dentin volume (similar to 30% incisor; 13% molar), and enamel and dentin mineral-density. Reactionary-tertiary-dentin in response to injury was reduced at Mmp13(-/-) molar cusp-tips but with significantly more dystrophic pulpal mineralization in MMP13-null samples. Odontoblast differentiation-markers, nestin and DSP, reduced in expression after MMP13-loss in vivo, with reduced calcium deposition in MMP13-null DPC cultures. RNA-sequencing analysis of WT and Mmp13(-/-) pulp highlighted 5,020 transcripts to have significantly >2.0-fold change, with pathway-analysis indicating downregulation of the Wnt-signaling pathway, supported by reduced in vivo expression of the Wnt-responsive gene Axin2. Mmp13 interaction with Axin2 could be partly responsible for the loss of odontoblastic activity and alteration to the tooth phenotype and volume which is evident in this study. Overall, our novel findings indicate MMP13 as critical for tooth development and mineralization processes, highlighting mechanistic interaction with the Wnt-signaling pathway.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据