Objective The present study was designed to investigate the whole transcriptome of periodontal tissues of both young and aged mice to identify the characteristic up‐regulation of protease genes with aging and to localize their translated protein products in the periodontal tissues. Background The metzincin protease superfamily is composed of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs. Up‐regulation of these extracellular matrix‐degrading proteases has been implicated in senescence of tissues and organs, including the skin. However, few studies have investigated the expression profiles of these proteases and potential involvement in aging of periodontal tissues. Methods Periodontal tissues with the surrounding mandibular bones were collected from 50‐ and 10‐week‐old mice. Total RNA was extracted from the periodontal tissue and analyzed by cap analysis of gene expression (CAGE) to identify differentially expressed genes encoding the metzincin proteases. Furthermore, quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to validate the CAGE results, and the phenotypic expression of proteases involved in aging was localized via immunohistochemical analysis. Results The CAGE results showed that the expression levels of MMP‐3, ‐10, and ‐12 were up‐regulated at 50 weeks. Subsequent qRT‐PCR analysis showed that the gene expression levels of MMP‐3 and ‐10 were significantly increased with age. MMP‐10 immunoreactivity was localized exclusively in the cementum and alveolar bone adjacent to the periodontal ligament and was stronger and broader in aged mice than young mice. MMP‐3 immunoreactivity was localized in the periodontal ligaments at both 10 and 50 weeks. Conclusion In the present study, we demonstrated that the expression of MMP‐3 and ‐10 increased with aging and identified their characteristic localizations in aged periodontal tissues.

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