Abstract
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.
Highlights
Osteoarthritis (OA) is a complex progressive degenerative joint disorder that accompanies cartilage degradation and physical disability (Sanchez et al, 2005; Sanchez et al, 2008; Jeon et al, 2017)
These findings demonstrate the suppressive effects of 3′-SL on the activated mitogen-activated protein kinases (MAPK) and phosphoinositol 3 kinase (PI3K)/AKT/NF-κB signaling in IL-1β-treated chondrocytic cells, which was presumably attributed to the suppression of oxidative stress and inflammation
Our data revealed that 3′-SL efficiently protects the cells from oxidative stress, inflammation, apoptosis, and cartilage matrix degradation by suppressing the activated MAPK and PI3K/AKT/NF-κB signaling pathways (Figure 7)
Summary
Osteoarthritis (OA) is a complex progressive degenerative joint disorder that accompanies cartilage degradation and physical disability (Sanchez et al, 2005; Sanchez et al, 2008; Jeon et al, 2017). The development and progression of OA are related to oxidative stress-induced cartilage damage and an imbalance between catabolic and anabolic factors in joints (Loeser, 2009; Appleton, 2018). The occurrence and development of OA have been studied extensively, there is currently no efficient therapy to prevent OA progression. Several studies have indicated that elevated oxidative stress and excessive generation of ROS are observed in OA patients (Altindag et al, 2007; Erturk et al, 2012; Altay et al, 2015)
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