Evaluating transglutaminase crosslinked collagen gel systems for hard and soft tissue repair

  • Nai Yeh

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Tissue Transglutaminase (TG2) and FXIIIa, members of the transglutaminase (TG) family,
catalyses a transamidating reaction and form covalent bond between or within proteins. In bone development, both enzymes expressions correlate with the initial of the mineralisation process by osteoblasts and chondrocytes. Exogenous TG2 also promotes
maturation of chondrocytes and mineralisation in pre-osteoblasts.
To understand the role of endogenous TG2 in osteoblast mineralisation, the TG2
expression was examined during the human osteoblast (HOB) mineralisation. The expression of the endogenous TG2 increased during the mineralisation, yet, its expression was not essential for mineral deposition due to the compensation effect by other
members in the TG family. The extracellular transamidating activity of HOBs was found increased during mineralisation and a shift from FXIIIa dominant- to TG2-dominant crosslinking activity was suggested after differentiation. However, the transamidating
activity of both TG2 and FXIIIa were not critical for cell mineralisation.
On the other hand, Exogenous TG2 was found to enhance wild type HOB and TG2 knockdown HOB mineral deposition. The transamidating activity of TG2 was not required but most likely a close conformation was essential for this enhancement. Results also
demonstrated that exogenous TG2 may activate the ß-catenin pathway through LRP5 receptor thus contribute in cell mineralisation. This enhancement could be abolished by addition of ß-catenin inhibitors. Finally, using of TG2 crosslinked collagen gel for bone and cornea repair was evaluated.
Crosslinked collagen gel showed promising results in improving HOB mineralisation, human corneal fibroblast (hCF) proliferation and migration. These effects might be
resulted from the trapped TG2 within the collagen matrix and the alteration of matrix topography by TG2.
Date of Award26 Sep 2013
Original languageEnglish
SupervisorRussell Collighan (Supervisor) & Martin Griffin (Supervisor)

Keywords

  • FXIIIa
  • close conformation
  • LRP5
  • β-catenin
  • human corneal fibroblast

Cite this

Evaluating transglutaminase crosslinked collagen gel systems for hard and soft tissue repair
Yeh, N. (Author). 26 Sep 2013

Student thesis: Doctoral ThesisDoctor of Philosophy