Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 45-56). Also available on the Internet.

Thesis (Ph. D.)--Rijksuniversiteit te Groningen. / eContent provider-neutral record in process. Description based on print version record.

Thesis (Ph. D.)--Rijksuniversiteit te Groningen. / eContent provider-neutral record in process. Description based on print version record.

Hand osteoarthritis (OA) is a degenerative joint disease that causes pain, functional limitation and negatively affects the patients' quality of life. The most severe subtype of this disease is erosive OA. Erosive hand OA is characterized by an abrupt onset, inflammation and is linked to worse outcomes than non-erosive hand OA. Current methods do not allow early diagnosis or to distinguish between patients with different forms at disease onset. This could be changed by the utilization of biomarkers in clinical practice. Biomarkers are molecules released into circulation that reflect biological processes. The main goal of this study was to analyze the levels of circulating biomarkers with the aim to differentiate patients from healthy subjects and patients with erosive OA from patients with non-erosive disease. Serum concentrations of seven biomarkers and the expression of plasma microRNAs were determined. Patients with hand OA showed altered cartilage metabolism, increased levels of adiponectin, decreased levels of clusterin and a dysregulated expression of several microRNAs in comparison to the healthy population. Patients with erosive OA had lower levels of clusterin and decreased expression of miR-151-3p than those with the non-erosive form of the disease. These findings suggest the potential...

<p>  </p> <p>Osteoarthritis (OA) is prevalent in equine and can be career-ending for performance horses due to lameness limitations and decreased quality of life. OA is a progressive, multifactorial disease that compromises the synovial joints' normal function, resulting in subchondral bone and articular cartilage deterioration over time. OA is a complex disease that impacts the entire joint, wherein activation of the innate immune system has an essential role in the disease progression and the development of pain. The synovial membrane, or the synovium, is a crucial contributor to the inflammation of diseased joints, regardless of the intra-articular tissue type initially affected. Synoviocytes are a predominant cell type of the synovium and contribute to inflammation by releasing key mediators and degradative enzymes, such as interleukin (IL)-6, IL-1β, a disintegrin, and metalloproteinase (ADAM) domains, and matrix metalloproteinases (MMPs). The production of pro-inflammatory molecules sequentially influences the expression of degradative enzymes and cartilage destruction. Therefore, the pathophysiological processes within synovial joints afflicted by OA can be further understood by studying the characteristics of synoviocytes.</p> <p>We aimed to investigate the inflammatory component of OA in an <em>in vitro</em> model using a primary cell line of equine fibroblast-like synoviocytes (eqFLS) stimulated with tumor necrosis factor-alpha (TNF-α) to represent an initial inflammatory stimulus. Our studies have shown that stimulating eqFLS with TNF-α for 24 hours significantly increased the gene expression of pro-inflammatory biomarkers. Among several pro-inflammatory candidate genes assayed, only pro-inflammatory cytokine IL-6 gene expression could be detected reproducibly following stimulation with the TNF-α gene in eqFLS. We characterized the pro-inflammatory response of eqFLS and utilized this system to examine the impact of novel therapeutic compounds designed <em>in-silico</em> with the goal of reducing the inflammatory response of eqFLS. A piperazine-based compound (C3) and its derivative (02-09) were primarily designed to mimic the interactions of the growth factor pigment epithelium-derived factor (PEDF) with its receptor, the non-integrin laminin receptor 1 (LAMR1). Based on previous <em>in vitro</em> studies in the laboratory, C3 and 02-09 had been proposed to have a strong potential for inhibiting inflammation while reducing angiogenesis and chondrocyte hypertrophy. The efficacy of these two novel compounds on eqFLS was examined in the present work by assessing the gene expression levels of inflammatory biomarkers, including IL-6, IL-1β, IL-8, ADAMs, and MMPs relative to a control housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in various study designs. An <em>in-vitro</em> screen with the IL-1β promoter driving a reporter green fluorescent protein (GFP) was also designed to detect and track the inflammatory response of eqFLS by imaging following stimulation with or without (+/-) TNF-α relative to controls. This screen will be utilized in future studies to potentially identify more effective compounds in the LAMR1-interacting series. The current findings suggest that the novel compounds, especially 02-09, might exhibit an anti-inflammatory effect on eqFLS; therefore, it is a potential therapeutic agent in modulating inflammation during OA development. </p> <p><br></p>

<p>Osteoarthritis (OA) is one of the most prevalent diseases in the United States and also in the world. Cartilage plays a vital role in articular joints and its structural integrity and mechanical properties are diminished by OA. Post traumatic osteoarthritis (PTOA) is a prevalent type of OA and occurs after a significant joint injury. Currently, no treatments are available to prevent or delay the progression of any form of OA.</p><p>Collagen crosslinking improves the material properties of cartilage and has been proposed as a potential treatment for OA. The wear resistance of cartilage that had been crosslinked with CASPc, a light activated crosslinking agent, was tested. Results suggested that photo-initiated crosslinking improves the wear characteristics of cartilage.</p><p>Another treatment for PTOA is through biological intervention. Preliminary data from our lab showed that metformin rescues the chondrocyte response to injurious impact overloading in the initial 24 hours following impact. However, whether this treatment maintained cartilage integrity for an extended duration had not been investigated. Material properties of cartilage were analyzed with an indentation test at different time points post-impact to determine the functional effect of cartilage injury and metformin treatment. Changes in the composition of the cartilage were investigated through biochemical techniques.</p><p>Having an in vivo model for PTOA is key for testing any new therapeutic intervention. In this study a model was developed to deliver a consistent impact load to the posterior aspect of medial condyle of a rabbit knee. A drop tower was designed for impacting the rabbit knee, and load and acceleration were measured during the impact. A k-wire was passed through the condyles in the medial-lateral direction under the impact site to secure the condyle during the impact. Whether the impact parameters were affected by the location of the k-wire was evaluated. The location of the k-wire was varied in the anterior/posterior and proximal/distal directions in a knee joint of cadaveric rabbits and impact parameters were recorded. Multiple linear regression showed a correlation between the location of the k-wire and peak stress, loading rate, impact duration and work. Moreover a correlation was found between the damage induced to the cartilage and loading rate, impact duration and peak stress. This study indicated that k-wire location is critical to prevent fracture of the subchondral bone.</p><p>A pilot study was designed to investigate the in-vivo effect of the metformin treatment on PTOA. Impacted knee joints in rabbits were treated with intraarticular metformin or were untreated controls. At 12 weeks post-injury, the progression of OA in the rabbit knees was quantified by histology, and OA severity was assessed using OA Research Society International (OARSI) scoring. Although the number of animals in the study were limited, intraarticular metformin appeared to prevent the development of PTOA in the impacted rabbit knees.</p>

[Truncated abstract] Knee osteoarthritis (OA) patients have high levels of pain, functional and strength deficits of the quadriceps, decreased proprioceptive acuity, and increased co-contraction and knee joint loading in gait, compared to age matched controls. The increased knee joint loading in this population occurs most commonly in the medial tibio-femoral compartment, due to increased external adduction moments, and with increasing disease severity there is a concomitant increase in the knee adduction moments. A key finding within the knee OA literature is that dynamic loading in gait, due to increased external adduction moments, strongly predicts pain and radiographic disease progression. Current research has shown that exercise interventions reduce pain and time to complete functional activities; however, the effect of these interventions on knee joint loading and muscular activation in gait is still unclear. In addition, the need for specific knee joint strengthening to cause these alterations has not been investigated and it remains unknown if improvements occur due to specific muscle strengthening or due to some general effect of exercise. Therefore, the primary aim of this research study was to examine the effects of general (upper body) and specific (lower body) resistance training interventions on self-perceived outcomes, neuromuscular function and kinematic, kinetic and muscle activation during gait of OA patients compared with asymptomatic controls. ... The examination of gait data following exercise (Study 4) showed trends for changes in the muscle co-contraction ratios. Specifically, the medial/lateral co-contraction ratio (MLCCR) displayed a trend in early stance where the upper body exercise group increased their lateral muscle activity and the lower body group reduced their lateral muscle activity, and the medial/lateral hamstring co-contraction ratio (HAMCCR) displayed this same trend during loading. The trend toward reduced lateral muscle activation, following lower body resistance training, suggests that specific muscle strengthening may have the ability to alter the load distribution. The kinematic and kinetic variables of gait were unchanged by the exercise interventions, highlighting the sensitivity of muscle activation pattern changes due to muscle strengthening. This thesis provides new insights into the co-contraction strategies utilised by knee OA patients. The directed co-contraction strategy employed by knee OA patients and its relationship to the external adduction moment in gait suggest an attempt to redistribute the loading within the knee joint, most likely in response to pain. Further, we have separated the effects of exercise and found differences in self-perceived outcomes based on exercise specificity. This first examination into muscle co-contraction following resistance training of knee OA patients has highlighted the possibility of alterations to the co-contraction patterns following lower body exercise. However, the implications of altering this muscle activation strategy and the consequent effect on distribution of load within the knee joint requires further consideration.

Master of Science / Department of Clinical Sciences / James K. Roush / The objective of this study was to evaluate the effects of intraarticular dextrose prolotherapy on osteoarthritis of the elbow or stifle in dogs. This was a randomized, double-blind, placebo controlled prospective trial of intraarticular dextrose prolotherapy given at 0 and 6 weeks for relief of osteoarthritis. Dogs with unilateral lameness were evaluated by orthopedic exam, visual lameness score, Canine Brief Pain Inventory (CBPI), goniometry, and by kinetic gait analysis at 0, 6 and 12 weeks. Joint radiographs were scored at 0 and 12 weeks. Ten client-owned dogs with naturally occurring osteoarthritis of the elbow or stifle were enrolled. Initial visual lameness, age, body weight, duration of lameness, and CBPI scores did not differ between groups. Change in CBPI PS score in the prolotherapy group from week 6-12 was significantly less improved than placebo with no other significant differences in CBPI Pain Severity (PS) or Pain Interference (PI) scores between groups. There were no significant differences for range of motion or radiographic scores between groups at any time. Kinetic forces improved in prolotherapy dogs, but were not significantly different between treatment groups at any time. There were no significant benefits of intraarticular dextrose prolotherapy for treatment of osteoarthritis of the elbow and stifle in dogs in this study. Larger enrollments and more stringent inclusion criteria should be considered in future evaluations of prolotherapy.

No description available.

This thesis investigated the cost-effectiveness of a 12-month supervised aerobic walking program with or without a behavioural intervention and an educational pamphlet, compared to an unsupervised/self-directed educational pamphlet intervention, among individuals with moderate osteoarthritis (OA) of the knee. Analyses included an economic evaluation to assess the cost effectiveness of the two walking interventions from both the societal and Canadian provincial/territorial health care payer perspectives. A value of information analysis exploring the potential value of future research was also performed. Results revealed that the unsupervised/self-directed intervention was the most cost-effective approach given that it cost the least to implement and participants had higher quality-adjusted life years (QALYs). Walking, either supervised in a community setting, or unsupervised in a setting such as the home, may be a favourable non-pharmacological option for the management of OA of the knee. The thesis concludes with a policy discussion relating to the funding of non-pharmacological therapies.