3′-Sialyllactose Protects SW1353 Chondrocytic Cells From Interleukin-1β-Induced Oxidative Stress and Inflammation

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.

Efficient Production of a Functional Human Milk Oligosaccharide 3′-Sialyllactose in Genetically Engineered Escherichia coli

“…Sialylated HMOs account for approximately 13% of total HMOs, in which 3′-sialyllactose (3′-SL), a representative and simplest one, is present at approximately 2%. , 3′-SL, structurally represented as Neu5Acα2,3Galβ1,4Glc, consists of N -acetylneuraminic acid (Neu5Ac) and lactose units. It has been widely confirmed to display promising prebiotic effects, antiadhesive antimicrobials, antiviral activity, preventing necrotizing enterocolitis (NEC), immunomodulatory, modulating intestinal epithelial cell response, and promoting brain development and improving cognition . The safety evaluation of 3′-SL has been widely studied in piglets, rats, and healthy humans.…”

Sialyllactose Prevents Cartilage Damages via M0 Macrophage Maintenance in Yucatan Mini-Pig Osteoarthritis Model

“…Moreover, there was a greater decrease in the expression of M1 and M2 specific markers in the 3' SL treatment group compared to the control group. Together, IL-1β induce osteoarthritic pathogenesis by oxidative stress and inflammation but 3'-Sialyllactose can suppress of oxidative stress and inflammation [27]. Thus, we demonstrated that 3' SL maintains the state of resting macrophages and protects from LPS-induced inflammation.…”

Current Advances in Structure–Function Relationships and Dose-Dependent Effects of Human Milk Oligosaccharides

“…HMOs also play important roles in regulating neonatal intestinal immunity, resisting viral , and bacterial infections, reducing anti-inflammatory responses, and promoting brain development . These functions are related to their structures to a certain extent, but to date, a comprehensive summary of the structure–function relationships of different types of HMOs has not been published.…”

“…For example, Baek et al. found that 3′-SL inhibited MAPK and PI3K/AKT/NF-κB signaling and downregulated oxidative stress and inflammation to alleviate IL-1β-induced osteoarthritis (OA) pathogenesis in a dose-dependent manner . Holscher et al constructed an intestinal epithelial cell model using HT-29 cells and Caco-2Bbe cells and explored the effect of three HMOs (2′-FL, 6′-SL, and LNnT) on intestinal cell maturation.…”