Abstract
Osteoarthritis (OA) is a common joint degenerative disease induced by oxidative stress in chondrocytes. Although induced-heme oxygenase-1 (HO-1) has been found to protect cells against oxygen radical damage, little information is available regarding the use of bioactive compounds from natural sources for regulating the HO-1 pathway to treat OA. In this study, we explored the inhibitory effects of cudratricusxanthone O (CTO) isolated from the Maclura tricuspidata Bureau (Moraceae) on H2O2-induced damage of SW1353 chondrocytes via regulation of the HO-1 pathway. CTO promoted HO-1 expression by enhancing the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus without inducing toxicity. Pretreatment with CTO-regulated reactive oxygen species (ROS) production by inducing expression of antioxidant enzymes in H2O2-treated cells and maintained the functions of H2O2-damaged chondrocytes. Furthermore, CTO prevented H2O2-induced apoptosis by regulating the expression of anti-apoptotic proteins. Treatment with the HO-1 inhibitor tin-protoporphyrin IX revealed that these protective effects were exerted due to an increase in HO-1 expression induced by CTO. In conclusion, CTO protects chondrocytes from H2O2-induced damages—including ROS accumulation, dysfunction, and apoptosis through activation of the Nrf2/HO-1 signaling pathway in chondrocytes and, therefore, is a potential therapeutic agent for OA treatment.
Highlights
Osteoarthritis (OA) is a chronic joint degenerative disease that affects normal movements due to loss of articular cartilage, in older adults [1,2]
SnPP-treated group (Figure 6B) and mRNA (Figure 6C). These results suggested that heme oxygenase-1 (HO-1) induced by cudratricusxanthone O (CTO) pretreatment in H2 O2 -stimulated SW1353 cells is involved in the regulation of Reactive oxygen species (ROS) production and recovery of antioxidant enzymes
The ROS inhibitory and anti-apoptotic effects of CTO as shown above, and the expression of antioxidant enzymes, were reversed. These results suggest that the protective effect on chondrocytes appears through Heme oxygenases (HOs)-1 expression by the activity of nuclear factor erythroid 2-related factor 2 (Nrf2) by CTO rather than by Nrf2 activity by H2 O2. These results suggest that, through activation of Nrf2 and HO-1, CTO could suppress ROS production and apoptosis as well as regulate antioxidant enzyme expression stimulated by H2 O2 in SW1353 cells
Summary
Osteoarthritis (OA) is a chronic joint degenerative disease that affects normal movements due to loss of articular cartilage, in older adults [1,2]. OA is accompanied by decomposition and destruction of the mesochondrium and cartilage, as well as synovial inflammation, but the main pathological reasons include oxidative stress, aging, and expression of inflammation-related genes [3]. Chondrocytes play an important role in maintaining the function of the joints and can generate tissue ECM—including collagen II and proteoglycan—to maintain tissue homeostasis and joint movement [5]. From a pathological point of view, the overproduction of ROS is associated with inflammation, atherosclerosis, Antioxidants 2020, 9, 788; doi:10.3390/antiox9090788 www.mdpi.com/journal/antioxidants
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