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The Role of Mitochondrial Reactive Oxygen Species in Chondrocyte Mechanotransduction

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posted on 2023-12-18, 16:00 authored by Aisha Momin
Articular cartilage is subjected to various loads which are required for healthy cartilage tissue maintenance. In vitro, mechanical stimulation has been used to apply loading to engineered constructs as a means of developing functional tissue. Chondrocytes, being mechano-sensitive cells, are able to sense external mechanical stimuli and respond in various ways through intracellular cascades by the process of mechanotransduction. Previous cartilage studies have demonstrated that mechanical stimulation causes mitochondrial deformation which leads to the production of mitochondrial reactive oxygen species (ROS). The work conducted in this thesis focused on elucidating the role of mitochondrial ROS as anabolic signalling molecules in chondrocyte mechanotransduction. The overall findings identified superoxide anion as the primary ROS produced from the ETC. Further inhibition studies demonstrated that chondrocyte matrix synthesis is dependent on ROS production, which can otherwise be supressed by ETC complex inhibitors. The link between ROS production and matrix biosynthesis was established through ROS-dependant activation of the p38 and JNK MAPK pathways. This anabolic synthetic response suggests that under short-term mechanical stimulation, ROS serve as important signalling molecules that are required for eliciting a positive biosynthetic response, primarily through MAPK pathways. iii

History

Language

eng

Degree

  • Master of Applied Science

Program

  • Biomedical Engineering

Granting Institution

Ryerson University

LAC Thesis Type

  • Thesis

Thesis Advisor

Stephen Waldman

Year

2021

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    Biomedical Engineering (Theses)

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