Effects of Exercise Therapy on Synovial Fluid Inflammation and Joint Tissue Health in Osteoarthritis Open Access
Eng, Tracy (Spring 2022)
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
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