Distribution of Cathepsin K in Late Stage of Tooth Germ Development and Its Function in Degrading Enamel Matrix Proteins in Mouse

Abstract

Cathepsin K (CTSK) is a member of cysteine proteinase family, and is predominantly expressed in osteoclastsfor degradationof bone matrix proteins. Given the similarity in physical properties of bone and dental mineralized tissues, including enamel, dentin and cementum, CTSK is likely to take part in mineralization process during odontogenesis. On the other hand, patients with pycnodysostosis caused by mutations of the CTSK gene displayedmultipledental abnormalities, such as hypoplasia of the enamel, obliterated pulp chambers, hypercementosis and periodontal disease. Thereforeitis necessary to study the metabolic role of CTSK in tooth matrix proteins. In this study, BALB/c mice at embryonic day 18 (E18), post-natal day 1 (P1), P5, P10 and P20 were used (5 mice at each time point)for systematic analyses of CTSK expression in the late stage of tooth germ development. We found that CTSK was abundantly expressed in the ameloblasts during secretory and maturation stages (P5 and P10) by immunohistochemistry stainings.During dentinogenesis, the staining was also intense in the mineralization stage (P5 and P10),but not detectable in the early stage of dentin formation (P1) and after tooth eruption (P20).Furthermore, through zymography and digestion test in vitro, CTSK was proved to be capable of hydrolyzing Emdogain and also cleaving Amelogenininto multiple products. Our resultsshed lights on revealing new functions of CTSK and pathogenesis of pycnodysostosis in oral tissues.

Methylation of Cdkn1c may be involved in the regulation of tooth development through cell cycle inhibition

“…In the Balb/c model, first molars at P1 and P3 were at the late bell stage, and at P5 and P7 were at the secretory stage (Fig. 2 a–d), similar to a previous report (Lv et al 2011 ; Jiang et al 2017 ). The bell stage is a crucial stage where epithelial-mesenchymal interactions culminate in dramatic morphological and functional changes (Liu et al 2017 ).…”

Pycnodysostosis: Natural history and management guidelines from 27 French cases and a literature review

“…In our study, orthodontic appliances were needed in 30% of cases. Enamel quality has also to be taken into account when dealing with pycnodysostosis teeth, since CTSK has been proven to degrade the enamel matrix proteins in mice …”

“…Enamel quality has also to be taken into account when dealing with pycnodysostosis teeth, since CTSK has been proven to degrade the enamel matrix proteins in mice. 21 Hearing loss has been reported in some cases of pycnodysostosis [22][23][24][25][26] and was found in 36% of the subjects. All of them were mild and most of them did not need any treatment, except for two patients (10%) who were prescribed hearing aid.…”

Genetic and Molecular Evaluation: Reporting Three Novel Mutations and Creating Awareness of Pycnodysostosis Disease

“…It was reported that mutations of the CTSK gene displayed multiple dental abnormalities, such as hypoplasia of the enamel, obliterated pulp chambers, and periodontal disease, none of which were found among our studied patients [28]. The observed dental findings included a high caries index of 75%, which could be attributed to the crowding and malposition of teeth.…”