Effects of Exercise Therapy on Synovial Fluid Inflammation and Joint Tissue Health in Osteoarthritis Öffentlichkeit

Abstract

Introduction: Osteoarthritis (OA) is a debilitating joint disease that leads to cartilage degradation, osteophyte formation and subchondral bone sclerosis. OA is characterized as an inflammatory condition due to cytokine signaling pathways that propagate joint tissue degradation. Exercise is the primary treatment for OA because of its ability to reduce pain and resolve systemic inflammation. However, there are two main caveats that lead to the misunderstanding of exercise’s effectiveness against OA: (1) differential exercise parameters used in pre-clinical and clinical testing leads to varying results in exercise’s therapeutic outcomes and (2) patient non-compliance prevents the realization of the long-term effectiveness of exercise. This thesis sought to standardize an exercise therapy regimen for a preclinical model to demonstrate the positive effects of exercise on joint tissue health. This exercise therapy was then applied to observe how various synovial cytokine levels may be altered with therapeutic exercise to identify potential pharmaceutical targets that could provide the benefits of exercise while overcoming the barrier of patient non-compliance. We hypothesized that a low-moderate exercise therapy would slow joint degradation and resolve intra-articular inflammation in a preclinical OA model.

Materials and Methods: A literature search of twenty-five (n=25) articles was conducted to determine the parameters of our preclinical exercise regimen. Medial meniscal transection (MMT) surgeries were performed on male Lewis rats to induce OA. Exercise groups performed mild treadmill walking for 30 min/day, 5 days/week at 10 m/min for 3 weeks, starting 3 weeks after surgery. Cartilage, osteophyte, and subchondral bone morphology of the medial tibia were analyzed with EPIC-micro CT. Spatiotemporal symmetry of gait was collected using EDGAR. Nineteen (n=19) inflammatory cytokines within the synovial fluid were measured and standardized using a multiplex ELISA array.

Results: MMT resulted in the development of OA, yet our established exercise protocol was able to improve both individual tissue morphological characteristics and overall tissue health in the MMT models. Exercise also maintained spatiotemporal symmetry. MMT altered synovial cytokine fluid levels, in which our exercise regimen was able to restore. Lead cytokines for morphological variation between exercised and non-exercised OA groups were IP-10 and IL-10, such that they accounted for 44% of the variability. Higher IP-10 levels were correlated with an anti-sclerotic response of the subchondral bone. IL-10 levels were positively associated with greater areas of exposed bone and osteophyte formation.

Discussion: Based on a literature search, we established an exercise regimen using mild treadmill walking to maintain joint tissue health, spatiotemporal symmetry, and intra-articular inflammation in a pre-clinical OA model. IP-10 and IL-10 were identified as lead cytokines in regulating cartilage breakdown, osteophyte formation and subchondral bone remodeling with respect to exercise. These findings demonstrate how therapeutic exercise can reduce intra-articular inflammation overall and how specific cytokine levels may dictate joint morphological changes.

Clinical Relevance: Exercise can slow disease progression of OA by shifting intra-articular cytokine levels back to a normal state. IP-10 and IL-10 level regulation could lead to a better understanding of exercise’s ability to reduce tissue degradation in OA.

Table of Contents

Introduction 8

Knee Joint Anatomy and Physiology 8

Osteoarthritis 10

Exercise Therapy Effectiveness Against OA 14

Exercise, Inflammation, and Joint Tissue Health 15

Caveats of Studying and Applying Exercise Therapy 15

Objectives and Significance 16

Materials and Methods 17

Aim 1: Develop a Preclinical Exercise Therapy Model for Post-Traumatic OA 17

Preclinical Exercise Model Literature Review 17

Exercise Regimen Determination 18

Preclinical OA Model Development 19

Exercise Therapy 20

Gait Analysis 21

Micro-CT and Histological Analysis 21

Statistical Analysis of Aim 1 22

Aim 2: Determination of Exercise Effects on OA Associated Inflammation 23

Synovial Fluid Collection 23

Statistical Analysis of Cytokines 24

Results 24

Aim 1: Develop a Preclinical Exercise Therapy Model for Post-Traumatic OA 24

Literature Review for Exercise Parameter Establishment 24

Exercise Compliance 25

Joint Functional Analysis 26

Exercise Effects on Tissue Morphology 27

Aim 2: Developed Exercise Regimen Effects on OA Associated Inflammation 29

Tissue Morphological Changes in Aim 2 29

Lead Cytokine Identification 30

Discussion 33

Supplementary Information 45

References 50

About this Honors Thesis

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School	Emory College
Department	Chemistry
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Health Sciences, Rehabilitation and Therapy Chemistry, Biochemistry
Stichwort	Inflammation Orthopaedics Joint Health Cytokines Knee Osteoarthritis Exercise Therapy
Committee Chair / Thesis Advisor	Jarred Kaiser, Emory University
Committee Members	Manuela Manetta, Emory University David Lynn, Emory University

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