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    Expression level of UCMA as a candidate molecular target in osteoarthritis
    (2021) Okuyan, H.M.; Arslan, Ahmet; Iğcı, Yusuf Ziya; Göğebakar, Bülent; Bilgiç, Nilüfer; Gündüz, Kübra; Sönmez, Dilara
    Aim: Osteoarthritis (OA) is a degenerative joint disorder that damages cartilage, synovium and subchondral bone, and there is yet no effective treatment for OA. The identification of novel therapeutic methods is crucially needed for better treatment of OA. Upper zone of growth plate and cartilage matrix associated (UCMA) was discovered as a chondrocyte specific protein in 2008, but its expression is solely not specific to cartilage tissue. Although UCMA is implicated in cartilage and bone metabolic processes, the molecular function of UCMA in OA is not elucidated yet. We aimed to examine the potential effect of UCMA in osteoblast metabolism associated with OA. Materials and Methods: We created an in vitro OA model by inducing osteoblast cell line with IL-1?. The expression levels of 12 related genes were determined using the qRT-PCR method. The MMP1 and OPG expression levels in the supernatants of cells were detected with ELISA. Results: We found that there was a dramatic increase in the levels of UCMA expression and other OA-related markers. We showed that IL-1? triggered the expression of main transcription factors playing a role during bone formation. MMP1 and OPG synthesis and secretions were increased in IL-1? induced-hFOB1.19 cell line significantly. Conclusion: Our study, as the first one using the human osteoblast cell line, provides good evidence about the potential value of UCMA in the pathophysiology of OA and shows that UCMA can be a promising molecular target to develop therapeutic approaches for OA.
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    In vivo protective effects of upper zone of growth plate and cartilage matrix associated protein against cartilage degeneration in a monosodium iodoacetate induced osteoarthritis model
    (Canadian Science Publishing, 2020) Okuyan, H.M.; Terzi, M.Y.; Karaboğa, İhsan; Doğan, S.; Kalacı, A.
    Osteoarthritis (OA) is a degenerative disease affecting the majority of over 65 year old people and characterized by cartilage degeneration, subchondral abnormal changes, and inflammation. Despite the enormous socioeconomic burden caused by OA, currently, there is no effective therapy against it. Upper zone of growth plate and cartilage matrix associated protein (UCMA) is a vitamin K dependent protein and has a critical role in pathophysiological conditions associated with bone and cartilage. However, there is no research on the protective role of intra-articular UCMA treatment in OA pathogenesis. Therefore, we aimed to investigate the potential therapeutic role of UCMA in an in vivo model of OA. We report for the first time that intra-articular UCMA injection ameliorated cartilage degeneration in a monosodium iodoacetate induced OA rat model. Furthermore, the OA-induced activation of nuclear factor kappa B and bone morphogenetic protein 2 signals was attenuated by UCMA. Our results indicated that UCMA decreased cartilage oligomeric matrix protein levels but did not affect interleukin 6, total antioxidant status, and total oxidant status levels in the serum. In conclusion, UCMA exhibited a therapeutic potential in the treatment of OA. This protective effect of UCMA is possibly achieved by reducing the aggrecanase activity and the production of inflammatory cytokines. © 2020, Canadian Science Publishing. All rights reserved.
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    Investigation of the protective effect of erdosteine against cyclosporine-induced injury in rat liver with histological and biochemical methods
    (Tubitak Scientific & Technical Research Council Turkey, 2015) Nacar, Ahmet; Karaboğa, İhsan; Okuyan, H.M.; Kaplan Sefil, Nebihat; Nacar, Emel; Motor, Sedat; Özkan, Orhan Veli
    Background/aim: In the present study, the protective effect of erdosteine against cyclosporine-induced injury in rat liver was investigated with histological and biochemical methods. Materials and methods: Thirty-two Wistar albino male rats were randomly divided into 4 groups: control (n = 8), cyclosporine (n = 8, 20 mg kg(-1) day(-1) i.p.), cyclosporine + erdosteine (n = 8, erdosteine 12 mg kg(-1) day(-1) orally), and erdosteine (n = 8). At the end of day 12, liver tissues were removed for histological and biochemical analysis. After liver tissues were fixed in 10% buffered neutral formalin, routine histological processes were applied and tissue sections were stained with hematoxylin and eosin, periodic acid-Schiff, and elastic fiber stain methods. One hundred lobules of liver were examined for each group and evaluated statistically. The levels of malondialdehyde and glutathione peroxidase, as well as the activities of superoxide dismutase, were determined. Results: The cyclosporine group showed significant histopathological changes compared to the control. In the cyclosporine + erdosteine group, histopathological changes of hepatic damage were markedly reduced. Histological findings were supported by biochemical results. Conclusion: Erdosteine could attenuate cyclosporine-induced liver injury.