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Updated: Sep 20, 2026
The Establishment of a Murine Mandibular Molar Extraction Socket Healing Model
Published on: January 13, 2023
Temporospatial gene expression and protein localization of matrix metalloproteinases and their inhibitors during
Nagako Yoshiba1, Kunihiko Yoshiba, Corinne Stoetzel
1Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Abstract:
The gene expression and protein distribution of matrix metalloproteinase (MMP) -2, -9, membrane type-1 MMP (MT1-MMP), as well as of TIMP-1, -2, and -3 were analyzed during mouse molar development. Immunohistochemical data demonstrated that all the MMPs investigated were expressed in the dental epithelium and mesenchyme. In contrast, gene and protein expression analysis for TIMPs showed that they were differentially expressed. TIMP-1 was expressed in the dental epithelium and mesenchyme between E13 and E16 and was transiently up-regulated at E14, the cap stage. TIMP-1 expression was also detected in differentiating odontoblasts. TIMP-2 RNA transcripts were found in the peridental and dental mesenchyme, odontoblasts, and ameloblasts. Protein analysis revealed high expression on the lingual side of the dental epithelium and underlying mesenchyme together with transient expression in the enamel knot at E14 and expression in the gingival tissue and enamel matrix postnatally. TIMP-3 RNA transcripts were found in discrete regions of the dental epithelium, including at high levels in the cervical loop at E16. Expression was also detected in preodontoblasts at E16 and transiently during ameloblast differentiation. Analysis of the protein distribution revealed a lower level of TIMP-3 on the lingual side of the dental epithelium at E14. MT1-MMP was expressed in the dental mesenchyme between E13 and E16, at relatively high levels in the cervical loop at E14, and in the odontoblasts and ameloblasts. The distinct temporospatial distribution patterns of the TIMPs suggest that these inhibitors play several intrinsic roles during tooth development.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are crucial for mouse molar development. Their distinct gene and protein expressions highlight key roles in dental tissue formation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Oral Biology
Background:
- Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), are critical regulators of extracellular matrix remodeling.
- Understanding their roles during tooth development is essential for insights into craniofacial morphogenesis.
Purpose of the Study:
- To investigate the gene expression and protein distribution of MMPs (-2, -9, MT1-MMP) and TIMPs (-1, -2, -3) during mouse molar development.
- To elucidate the specific spatiotemporal patterns of these molecules in dental tissues.
Main Methods:
- Immunohistochemistry was used to analyze protein distribution.
- Gene expression analysis (RNA transcripts) was performed for TIMPs.
- Analysis covered key developmental stages from embryonic day 13 (E13) to postnatal stages.
Main Results:
- All investigated MMPs were expressed in dental epithelium and mesenchyme.
- TIMPs showed differential expression patterns: TIMP-1 in epithelium/mesenchyme and odontoblasts; TIMP-2 in mesenchyme, odontoblasts, ameloblasts, and enamel matrix; TIMP-3 in epithelium, cervical loop, preodontoblasts, and ameloblasts.
- MT1-MMP was found in mesenchyme, cervical loop, odontoblasts, and ameloblasts.
Conclusions:
- The distinct temporospatial expression patterns of TIMPs suggest multifaceted intrinsic roles during tooth development.
- These findings contribute to understanding the molecular mechanisms governing dental morphogenesis.
