Background: Knee osteoarthritis (OA) is the most common form of arthritis in older adults. Knee OA is associated with limitations in physical function. Functional limitations are also associated with another geriatric condition, frailty. Frailty is characterized by reduced strength, endurance and physiological function. Purpose: The primary purpose of this study is to determine if there is a difference in radiographic or symptomatic knee OA severity between non-frail and pre-frail women with knee OA. Secondary objectives include: a) the relationship between radiographic and symptomatic OA severity with serum inflammatory cytokines, and b) if there is a difference in inflammatory cytokines between non-frail and pre-frail women with knee OA. Methods: We included 21 community-dwelling women with knee OA. Frailty was assessed using the Fried Frailty Phenotype. Knee OA severity was characterized by the Kellgren and Lawrence (KL) score and the Knee Injury and Osteoarthritis Outcome Questionnaire (KOOS). Inflammatory cytokines included serum interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis alpha (TNF α) and C reactive protein (CRP). Results: Data from 20 participants (66.1 [9.6] years, BMI 29.7 [4.9] kg/m2, non-frail=55%; pre-frail=45%) were analyzed. Radiographic severity was not different between frailty groups (p= 0.11). There was no difference in symptomatic knee OA severity, measured using the KOOS subscales, between frailty groups (p>0.17). Radiographic OA severity and inflammatory markers were not associated (p>0.30). There was a negative relationship between TNF α and self-reported pain (r=0.26), no relationships between inflammatory cytokines with any other KOOS sub-scales. Lastly, there was no difference in any inflammatory cytokines between non-frail and pre-frail groups. Conclusion: Despite the relatively young age, nearly 50% of our participants were pre-frail. Pre-frailty was unrelated to the severity of the knee OA, or inflammatory cytokines. TNF α may be involved in the experience of pain in these women. While it appears women with knee OA frequently demonstrate pre-frail status, more work is necessary to examine the link between these diseases. / Thesis / Master of Science (MSc) / Arthritis is a chronic disease that has a debilitating effect on the lives of more than 4.6 million Canadians. In 2015, the cumulative economic burden of osteoarthritis was 195.2 billion dollars and is expected to increase significantly in the next two years. Knee osteoarthritis is the most common form of arthritis in older adults. Knee osteoarthritis is associated with increased pain, decreased physical function and decreased quality of life (QOL). In vulnerable older adults increased exhaustion, decreased physical function and muscle loss can increase the risk of developing frailty. Frail older adults are at higher risk of adverse health outcomes such as falls, hospitalization and death. Previous research has shown that older adults with knee OA are at higher risk of developing frailty however, it is not understood what underlying mechanisms increase this risk. This thesis provides fundamental information aimed at understanding potential mechanisms associated with knee osteoarthritis and frailty in women. Our study found that despite their relatively young age, nearly half of the women with knee OA are pre-frail. This data shows that inflammatory cytokines in particular, tumor necrosis factor alpha is related to symptomatic knee osteoarthritis severity in particular, self-reported pain. Overall, early detection of frailty is important when managing this condition. These data suggest that chronic knee pain associated with OA may be a useful trigger for early assessments of frailty in women.

L'interleukine-17A (IL-17A) et le facteur de nécrose tumorale alpha (TNF-α) sont des cytokines pro-inflammatoires impliquées dans la pathogénèse de plusieurs maladies articulaires. Au cours de la polyarthrite rhumatoïde (PR), une augmentation de la destruction osseuse ainsi qu'un defaut de réparation sont responsables des dommages articulaires. Cependant au cours de la spondylarthrite ankylosante (AS), une importante ossification ectopique est observée, conduisant à la formation de syndesmophytes, associé à une perte de la masse osseuse systémique. Récemment, l'étude de ces cytokines a conduit à la publication de résultats contradictoires. Notre objectif a donc été d'étudier l'effet de ces deux cytokines sur la différenciation ostéogénique de cellules souches mésenchymateuses humaines isolées (hMSCs) et de fibroblastes de la membrane synoviale (FLS). Tous les modèles de cellules utilisés, ont démontré que l'IL-17A et le TNF-α augmentent de manière synergique l'ostéogénèse. Ceci semble se rapprocher du modèle de l'AS où une formation d'os ectopique est observée dans laquelle l'IL-17A et le TNF-α jouent un rôle majeur. En parallèle, ces deux cytokines stimulent localement les ostéoclastes, entraînant une perte de masse osseuse observée à la fois dans la PR et dans l'ostéoporose. Cibler simultanément l'IL-17A et le TNF-α pourrait conduire à une diminution de l'infiltration de cellules et de la destruction articulaire observée dans la PR et pourrait ainsi réduire les effets des FLS PR sur l'activation de l'ostéoclastogénèse / Interleukin-17A (IL-17A) and tumor necrosis factor alpha (TNF-α) are pro-inflammatory cytokines involved in the pathogenesis of several arthritic diseases. In rheumatoid arthritis (RA), joint damage is a result of an increase in bone destruction and a decrease in bone repair. In contrast, in ankylosing spondylitis (AS), a bone mass loss accompanied by a significant ectopic ossification is observed leading to the formation of syndesmophytes. Recent studies led to contradictory findings regarding the role of IL-17A and TNF-α in arthritic disease. Therefore, our objective was to study the effect of these two cytokines on the osteogenic differentiation of isolated human mesenchymal stem cells (hMSCs) and fibroblasts of the synovial membrane (FLS). In all the cell models used, we demonstrated that Il-17A and TNF α synergistically increase osteogenesis. This seems to approach the model of AS where ectopic bone formation is observed and in which IL-17A and TNF-α both are involved. These cytokines stimulate osteoclasts locally resulting in loss of bone mass observed in both RA and osteoporosis. Thus, targeting IL-17A and TNF-α could lead to a decrease in cell infiltration and joint destruction which is observed in RA and may reduce the effects of RA FLS on the activation of osteoclastogenesis