Date of Award

2019

Embargo Period

8-1-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Oral Health Sciences

College

College of Graduate Studies

First Advisor

Amy D. Bradshaw

Second Advisor

Robin Muise-Helmericks

Third Advisor

James Cray

Fourth Advisor

Amanda C. LaRue

Fifth Advisor

Christine B. Kern

Abstract

The collagen fibers that span the periodontal ligament (PDL) connect teeth to the bone socket by weaving through the cementum of each tooth as well as into the alveolar bone. Collagen type I is the main structural component of the PDL. High rates of extracellular matrix (ECM) turnover are characteristic of PDL tissue. Periodontal disease (PD) afflicts approximately 50% of the population in the United States. PD is marked by chronic inflammation of the periodontium leading to PDL degradation, alveolar bone loss, and eventual tooth loss. There are currently no accepted methodologies to regenerate this collagenous PDL tissue. Thus PDL provides an excellent tissue milieu for investigating mechanisms of collagen processing and assembly during inflammatory states that are clinically relevant. SPARC, a collagen-binding protein, has been identified as a key factor in collagen ECM deposition. We reported that SPARC-null mice have significantly less total collagen, thinner collagen fibers, and reduced mechanical strength in PDL compared to wild type (WT) PDL. A key factor in incorporation and stabilization of insoluble collagen within the ECM is mediated through collagen cross-linking. Transglutaminases (TGs) are a family of extracellular proteins known to participate in collagen cross-linking activity in vitro and in vivo. Previous data implicate SPARC as a critical regulator of TG activity on collagen I in homeostatic PDL. Inhibition of TG activity in vivo was shown to reverse SPARC-dependent decreases in collagen volume fraction and mechanical strength of homeostatic PDL. Our data predicts SPARC regulates TG activity by mediating substrate specificity in the ECM.

Rights

All rights reserved. Copyright is held by the author.

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