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Role of Keratin-75 in enamel

Deshmukh, Rutuja (2021) Role of Keratin-75 in enamel. Master's Thesis, University of Pittsburgh. (Unpublished)

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Enamel is one of the primary tissues of the tooth and is the hardest tissue in the human body. Even though the enamel organic matrix accounts only for 1% of the mature enamel by weight, numerous studies have demonstrated that the components of the organic material are vital for the structural and mechanical properties of the enamel. Dental caries is an irreversible microbial disease affecting the majority of the population. Even though it is described as a multifactorial disease, there are strong pieces of evidence suggesting the impact of genetic factors on the susceptibility of the tooth to dental caries. Epithelial hair keratin KRT75 has been recently discovered in the enamel organic matrix. It was observed that carriers of A161T in KRT75 leading to Pseudofollicullitis barbae also have altered enamel microstructure and mechanical properties along with higher susceptibility to caries. The proposed aims were designed to address the question regarding the effects of KRT75 on structural and mechanical properties of the enamel and to assess the susceptibility of the enamel to acid attack by using a mouse model of Pachynonychia congenita - Krt75tm1Der knock-in with deletion of Asparagine at 159 which is only 2 amino acids away from KRT75A161T in humans.
The total mineral density in one-month and 10-month age group was significantly different in KI vs WT. It was significantly lower in ten-month-old in KI, and there was no significant age related decrease in the WT, suggesting that the enamel in KI is more soluble than in WT.
In both genotypes the enamel volume was significantly lower in ten-month-old animals. This observation demonstrates that in mice, enamel undergoes significant wear in the first year of their life. The Vickers microhardness was lower in KI vs WT indicating that KI enamel is softer. The results of the in vitro acid attack experiment were inconclusive, potentially due to long exposure times but they provide some clues that KI enamel is more susceptible to dissolution, however more experiments need to be done. Overall our studies demonstrate that the mutation in Krt75 gene negatively affects the chemical and mechanical properties of murine enamel.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Deshmukh, Rutujarcd36@pitt.edurcd36
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBeniash, Eliaebeniash@pitt.eduebeniash
Committee MemberMargolis, Henryhmargolis@pitt.eduhmargolis
Committee MemberAlejandro, Alamarzaaja19@pitt.eduaja19
Date: 3 September 2021
Date Type: Publication
Defense Date: 27 July 2021
Approval Date: 3 September 2021
Submission Date: 24 July 2021
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 71
Institution: University of Pittsburgh
Schools and Programs: School of Dental Medicine > Dental Science
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Enamel, KRT75, Dental caries, keratins
Date Deposited: 03 Sep 2021 17:43
Last Modified: 03 Sep 2023 05:15

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