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The Role of Ligaments in Murine Osteoarthritic Models: Markers and Mechanics.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Role of Ligaments in Murine Osteoarthritic Models: Markers and Mechanics./
作者:	Ramos Mucci, Lorenzo.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	255 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-02, Section: B.
Contained By:	Dissertations Abstracts International83-02B.
標題:	Tomography. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28605637
ISBN:	9798522949518

The Role of Ligaments in Murine Osteoarthritic Models: Markers and Mechanics.
Ramos Mucci, Lorenzo.

The Role of Ligaments in Murine Osteoarthritic Models: Markers and Mechanics. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 255 p.

Source: Dissertations Abstracts International, Volume: 83-02, Section: B.

Thesis (Ph.D.)--The University of Liverpool (United Kingdom), 2021.

This item must not be sold to any third party vendors.

Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability among elderly. It is a multicomponent chronic disease and yet little is known about the role of ligaments in OA. Ligaments are the main mechanical stabilizers of the knee joint, and trauma of the ligament has been closely linked to OA making it a potential target for therapeutics. Cellular, matrix and mechanical pathology of the ligament have not been fully characterised in OA. Furthermore, ligament cellular complexity remains poorly understood, including identification of ligament cell populations and markers in healthy, non-diseased tissue. Understanding the healthy ligament is essential to understand the pathology of diseased OA ligaments.The goal of this thesis was to characterise and identify markers and mechanical properties in the ligaments in healthy and diseased spontaneous and post-traumatic OA murine models. Histology demonstrated changes in anterior cruciate ligament (ACL) and the medial collateral ligament (MCL) organization and cell morphology between healthy and OA ligaments. In the extracellular matrix (ECM) of diseased ligaments, pathology included proteoglycan and collagen type II (COL2) deposition. ECM pathology coincided with rounded-cell morphology and SOX9 and RUNX2 expression, markers of chondrogenesis, and potentially endochondral ossification. Changes occurred in the early stages of OA, suggesting an important role of ligaments in OA.Functional changes to the mechanical properties of the ligaments were explored in healthy and diseased OA models. Viscoelastic behaviour demonstrated a decrease in normalised strain rate sensitivity in both the spontaneous and post-traumatic OA ACLs. Furthermore, there was a decrease in stiffness and stress-relaxation in the post-traumatic OA ACL. These findings confirm that ligament ECM composition and viscoelastic properties are closely interrelated. Understanding the underlying pathways driving viscoelastic properties is imperative for OA. Single-cell RNA-sequencing (scRNA-seq) identified ligament cell populations and gene markers from healthy adult mice knee ligaments. Analysis revealed 20 distinct clusters and nine cell types, from which there were five fibroblast clusters. Most importantly, the smallest fibroblast cluster, included Aggrecan (Acan) as well as Sox9 and Col2a1 gene markers previously seen in diseased OA ligaments. ACAN-expressing fibroblasts were confirmed in the mid-ligament section of murine cruciate ligaments. The role of this novel fibroblast subpopulation in OA is unknown.This research introduces a deeper understanding of healthy and OA ligament, including cellular and fibroblast markers, ECM composition and viscoelastic properties, all which indicate that ligaments play a bigger role in OA than previously thought.

ISBN: 9798522949518Subjects--Topical Terms:

836553
Tomography.

The Role of Ligaments in Murine Osteoarthritic Models: Markers and Mechanics.
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520 $a Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability among elderly. It is a multicomponent chronic disease and yet little is known about the role of ligaments in OA. Ligaments are the main mechanical stabilizers of the knee joint, and trauma of the ligament has been closely linked to OA making it a potential target for therapeutics. Cellular, matrix and mechanical pathology of the ligament have not been fully characterised in OA. Furthermore, ligament cellular complexity remains poorly understood, including identification of ligament cell populations and markers in healthy, non-diseased tissue. Understanding the healthy ligament is essential to understand the pathology of diseased OA ligaments.The goal of this thesis was to characterise and identify markers and mechanical properties in the ligaments in healthy and diseased spontaneous and post-traumatic OA murine models. Histology demonstrated changes in anterior cruciate ligament (ACL) and the medial collateral ligament (MCL) organization and cell morphology between healthy and OA ligaments. In the extracellular matrix (ECM) of diseased ligaments, pathology included proteoglycan and collagen type II (COL2) deposition. ECM pathology coincided with rounded-cell morphology and SOX9 and RUNX2 expression, markers of chondrogenesis, and potentially endochondral ossification. Changes occurred in the early stages of OA, suggesting an important role of ligaments in OA.Functional changes to the mechanical properties of the ligaments were explored in healthy and diseased OA models. Viscoelastic behaviour demonstrated a decrease in normalised strain rate sensitivity in both the spontaneous and post-traumatic OA ACLs. Furthermore, there was a decrease in stiffness and stress-relaxation in the post-traumatic OA ACL. These findings confirm that ligament ECM composition and viscoelastic properties are closely interrelated. Understanding the underlying pathways driving viscoelastic properties is imperative for OA. Single-cell RNA-sequencing (scRNA-seq) identified ligament cell populations and gene markers from healthy adult mice knee ligaments. Analysis revealed 20 distinct clusters and nine cell types, from which there were five fibroblast clusters. Most importantly, the smallest fibroblast cluster, included Aggrecan (Acan) as well as Sox9 and Col2a1 gene markers previously seen in diseased OA ligaments. ACAN-expressing fibroblasts were confirmed in the mid-ligament section of murine cruciate ligaments. The role of this novel fibroblast subpopulation in OA is unknown.This research introduces a deeper understanding of healthy and OA ligament, including cellular and fibroblast markers, ECM composition and viscoelastic properties, all which indicate that ligaments play a bigger role in OA than previously thought.
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