3′-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1β-Induced Oxidative Stress and Inflammation
Osteoarthritis (OA) is a major degenerative joint disease. Oxidative stress and inflammation play key roles in the pathogenesis of OA. 3′-Sialyllactose (3′-SL) is derived from human milk and is known to regulate a variety of biological functions related to immune homeostasis. This study aimed to inv...
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Frontiers Media S.A.
2021-04-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.609817/full |
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author | Ahreum Baek Ahreum Baek So Hee Jung Soonil Pyo Soonil Pyo Soo Yeon Kim Seongmoon Jo Seongmoon Jo Lila Kim Eun Young Lee Sung Hoon Kim Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho |
author_facet | Ahreum Baek Ahreum Baek So Hee Jung Soonil Pyo Soonil Pyo Soo Yeon Kim Seongmoon Jo Seongmoon Jo Lila Kim Eun Young Lee Sung Hoon Kim Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho |
author_sort | Ahreum Baek |
collection | DOAJ |
description | Osteoarthritis (OA) is a major degenerative joint disease. Oxidative stress and inflammation play key roles in the pathogenesis of OA. 3′-Sialyllactose (3′-SL) is derived from human milk and is known to regulate a variety of biological functions related to immune homeostasis. This study aimed to investigate the therapeutic mechanisms of 3′-SL in interleukin-1β (IL-1β)-treated SW1353 chondrocytic cells. 3′-SL potently suppressed IL-1β-induced oxidative stress by increasing the levels of enzymatic antioxidants. 3′-SL significantly reversed the IL-1β mediated expression levels of reactive oxygen species in IL-1β-stimulated chondrocytic cells. In addition, 3′-SL could reverse the increased levels of inflammatory markers such as nitrite, prostaglandin E2, inducible nitric oxide synthase, cyclooxygenase-2, IL-1β, and IL-6 in IL-1β-stimulated chondrocytic cells. Moreover, 3′-SL significantly inhibited the apoptotic process, as indicated by the downregulation of the pro-apoptotic protein Bax, upregulation of the anti-apoptotic protein Bcl-2 expression, and significant reduction in the number of TUNEL-positive cells in the IL-1β-treated chondrocytic cells. Furthermore, 3′-SL reversed cartilage destruction by decreasing the release of matrix metalloproteinases (MMP), such as MMP1, MMP3, and MMP13. In contrast, 3′-SL significantly increased the expression levels of matrix synthesis proteins, such as collagen II and aggrecan, in IL-1β-treated chondrocytic cells. 3′-SL dramatically suppressed the activation of mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways, which are related to the pathogenesis of OA. Taken together, our data suggest that 3′-SL alleviates IL-1β-induced OA pathogenesis via inhibition of activated MAPK and PI3K/AKT/NF-κB signaling cascades with the downregulation of oxidative stress and inflammation. Therefore, 3′-SL has the potential to be used as a natural compound for OA therapy owing to its ability to activate the antioxidant defense system and suppress inflammatory responses. |
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spelling | doaj.art-a9e1700dd1ee4d43ab63bcdae52c42e72022-12-21T21:25:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.6098176098173′-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1β-Induced Oxidative Stress and InflammationAhreum Baek0Ahreum Baek1So Hee Jung2Soonil Pyo3Soonil Pyo4Soo Yeon Kim5Seongmoon Jo6Seongmoon Jo7Lila Kim8Eun Young Lee9Sung Hoon Kim10Sung-Rae Cho11Sung-Rae Cho12Sung-Rae Cho13Sung-Rae Cho14Department of Rehabilitation Medicine, Yonsei University Wonju College of Medicine, Wonju, KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, KoreaDepartment of Rehabilitation Medicine, The Graduate School Yonsei University Wonju College of Medicine, Wonju, KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, KoreaDepartment of Medicine, Yonsei University Wonju College of Medicine, Wonju, South KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, KoreaGeneChem Inc., Daejeon, KoreaDepartment of Rehabilitation Medicine, The Graduate School Yonsei University Wonju College of Medicine, Wonju, KoreaDepartment of Rehabilitation Medicine, Yonsei University Wonju College of Medicine, Wonju, KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, KoreaGraduate Program of Nano Science and Technology, Yonsei University College of Medicine, Seoul, KoreaRehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, KoreaOsteoarthritis (OA) is a major degenerative joint disease. Oxidative stress and inflammation play key roles in the pathogenesis of OA. 3′-Sialyllactose (3′-SL) is derived from human milk and is known to regulate a variety of biological functions related to immune homeostasis. This study aimed to investigate the therapeutic mechanisms of 3′-SL in interleukin-1β (IL-1β)-treated SW1353 chondrocytic cells. 3′-SL potently suppressed IL-1β-induced oxidative stress by increasing the levels of enzymatic antioxidants. 3′-SL significantly reversed the IL-1β mediated expression levels of reactive oxygen species in IL-1β-stimulated chondrocytic cells. In addition, 3′-SL could reverse the increased levels of inflammatory markers such as nitrite, prostaglandin E2, inducible nitric oxide synthase, cyclooxygenase-2, IL-1β, and IL-6 in IL-1β-stimulated chondrocytic cells. Moreover, 3′-SL significantly inhibited the apoptotic process, as indicated by the downregulation of the pro-apoptotic protein Bax, upregulation of the anti-apoptotic protein Bcl-2 expression, and significant reduction in the number of TUNEL-positive cells in the IL-1β-treated chondrocytic cells. Furthermore, 3′-SL reversed cartilage destruction by decreasing the release of matrix metalloproteinases (MMP), such as MMP1, MMP3, and MMP13. In contrast, 3′-SL significantly increased the expression levels of matrix synthesis proteins, such as collagen II and aggrecan, in IL-1β-treated chondrocytic cells. 3′-SL dramatically suppressed the activation of mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways, which are related to the pathogenesis of OA. Taken together, our data suggest that 3′-SL alleviates IL-1β-induced OA pathogenesis via inhibition of activated MAPK and PI3K/AKT/NF-κB signaling cascades with the downregulation of oxidative stress and inflammation. Therefore, 3′-SL has the potential to be used as a natural compound for OA therapy owing to its ability to activate the antioxidant defense system and suppress inflammatory responses.https://www.frontiersin.org/articles/10.3389/fphar.2021.609817/fullosteoarthritis3′-sialyllactoseoxidative stressinflammationapoptosismatrix metalloproteinases |
spellingShingle | Ahreum Baek Ahreum Baek So Hee Jung Soonil Pyo Soonil Pyo Soo Yeon Kim Seongmoon Jo Seongmoon Jo Lila Kim Eun Young Lee Sung Hoon Kim Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho 3′-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1β-Induced Oxidative Stress and Inflammation Frontiers in Pharmacology osteoarthritis 3′-sialyllactose oxidative stress inflammation apoptosis matrix metalloproteinases |
title | 3′-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1β-Induced Oxidative Stress and Inflammation |
title_full | 3′-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1β-Induced Oxidative Stress and Inflammation |
title_fullStr | 3′-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1β-Induced Oxidative Stress and Inflammation |
title_full_unstemmed | 3′-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1β-Induced Oxidative Stress and Inflammation |
title_short | 3′-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1β-Induced Oxidative Stress and Inflammation |
title_sort | 3 sialyllactose protects sw1353 chondrocytic cells from interleukin 1β induced oxidative stress and inflammation |
topic | osteoarthritis 3′-sialyllactose oxidative stress inflammation apoptosis matrix metalloproteinases |
url | https://www.frontiersin.org/articles/10.3389/fphar.2021.609817/full |
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