Sarkytbayev, Kuanysh2024-06-112024-06-112024-04-26Sarkytbayev, K. (2024). Investigating the role of periostin in rheumatoid arthritis. Nazarbayev University School of Medicinehttp://nur.nu.edu.kz/handle/123456789/7828Rheumatoid Arthritis (RA) is a chronic inflammatory disease, in which the immune system of the organism attacks its own tissue on different body parts (Finckh et al. 2022). Mostly, RA affects the joints of hands, feet, knees, shoulders, etc. According to the World Health Organization, in 2019, about 18 million people worldwide had RA and 70% were women (“Rheumatoid Arthritis,” n.d.). The specific causes of the disease are unknown, but several disease-associated risk factors have been identified, like, smoking, obesity, genetics, gender, and age (Weyand and Goronzy 2021). There are a few publications suggesting some possible roles of periostin in RA disease progression (Brown et al. 2018). Periostin is an extracellular matrix protein that has varying roles in inflammation and tissue remodeling (Sonnenberg-Riethmacher, Miehe, and Riethmacher 2021). It was revealed that periostin is upregulated in synovial cells and fluid of RA patients, which suggests that it may worsen inflammatory conditions in the RA affected body parts (Chijimatsu et al. 2015; Kasperkovitz et al. 2005). However, there are some studies that provide contradictory evidence, which demonstrate after artificial induction of RA in mice, disease progression is more severe in periostin-deficient mice compared to wild-type mice. So, the precise function of periostin in RA pathogenesis remains enigmatic. The aim of this master thesis project was to elucidate the unknown role of the periostin in the RA progression and examine its potential anti-inflammatory properties. Firstly, it was planned to establish a mouse model of rheumatoid arthritis to investigate the comprehensive role of periostin in the disease progression (Caplazi et al. 2015). For this purpose, RA was induced in wild-type and periostin-deficient mice using a collagen-induced arthritis method (Brand, Latham, and Rosloniec 2007; Inglis et al. 2008). After the RA induction, mice were monitored for the disease progression based on the 3 assessment methods: measurement of paw thickness, observation of walking and behavior, and palpation. Then, mice were euthanized and inflamed joints were used for the comparative analysis. Expression of periostin and IL-17 receptor A were analyzed with fluorescent immunohistochemistry. For the histopathological analysis, hematoxylin and eosin staining was implemented to identify structural differences in the inflamed tissue joints. This master thesis project contributes to advancing the knowledge of the periostin role in RA pathogenesis.enAttribution-NonCommercial-NoDerivs 3.0 United StatesType of access: Embargoperiostinrheumatoid arthritisinflammationsynoviumfibroblastMaster's thesis