Protective Effects of Garlic-Derived S-Allylmercaptocysteine on IL-1β-Stimulated Chondrocytes by Regulation of MMPs/TIMP-1 Ratio and Type II Collagen Expression via Suppression of NF-κB Pathway

Yang, Guang; Li, Siying; Li, Bin; Cheng, Lin; Peng, Jiang; Tian, Zhoubin

doi:10.1155/2017/8686207

Cited by 16 publications

(11 citation statements)

References 42 publications

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“…Studies have shown that IL-1β plays an important role in the progression of OA by promoting the degeneration and apoptosis of chondrocytes, and it has been widely used to establish OA cell models 15, 16. This is consistent with our results showing that IL-1β stimulated miR-10a-5p expression in both human and murine primary chondrocytes.…”

Section: Discussionsupporting

confidence: 92%

miR-10a-5p Promotes Chondrocyte Apoptosis in Osteoarthritis by Targeting HOXA1

Chen

et al. 2019

Molecular Therapy - Nucleic Acids

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Osteoarthritis (OA) is a common joint disease characterized by degradation of the articular cartilage and joint inflammation. Studies have revealed the importance of microRNAs in the regulation of chondrocyte apoptosis. MicroRNA deep sequencing of control and osteoarthritic cartilage has revealed that miR-10a-5p is significantly upregulated in osteoarthritic tissues. However, its role in these tissues remains unknown. The present study was conducted to investigate the effect of miR-10a-5p in promoting OA. miR-10a-5p expression was increased in chondrocytes after interleukin-1β treatment in vitro. Transfection with a miR-10a-5p inhibitor abrogated interleukin-1β-induced apoptosis. A luciferase activity assay showed that miR-10a-5p targeted the 3′ UTR of the homeobox gene HOXA1, inhibiting its expression. Treatment with HOXA1 siRNA reversed the rescuing effect of the miR-10a-5p inhibitor on chondrocyte apoptosis. Additionally, an OA model was established in mice by anterior cruciate ligament transection. AntagomiR-10a-5p improved the cartilage surfaces of osteoarthritic mice, whereas agomiR-10a-5p worsened them. A terminal deoxynucleotidyl transferase dUTP nick-end labeling assay indicated reduced apoptosis and increased HOXA1 expression in osteoarthritic mice after miR-10a-5p knockdown. These findings reveal a novel mechanism regulating OA progression and demonstrate the potential of miR-10a-5p and homeobox protein HOXA1 as therapeutic targets.

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Section: Discussionsupporting

confidence: 92%

miR-10a-5p Promotes Chondrocyte Apoptosis in Osteoarthritis by Targeting HOXA1

Chen

et al. 2019

Molecular Therapy - Nucleic Acids

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“…Immunohistochemistry examination was carried out as previously described. 6 Briefly, sections were deparaffinized, rehydrated, and blocked with 10% normal goat serum. Then the primary antibody (anti-rat Col II antibody, anti-p65 antibody, Abcam) were incubated overnight, following biotin-labeled secondary antibodies for 1 hour at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…Chondrocytes isolation was conducted as previously described with modification. 6 Primary rat chondrocytes were seeded in 6-well plates. Nrf2 loss-of-function approaches were achieved by infecting the cells with adenovirus of miNrf2 (Ad-miNrf2) and miScramble (Ad-Scramble) 11 in serum free DMEM for 8 hours and then changed to DMEM supplemented with 10% FBS.…”

Section: Methodsmentioning

confidence: 99%

S-Allylmercaptocysteine Targets Nrf2 in Osteoarthritis Treatment Through NOX4/NF-κB Pathway

Yang¹,

Wang²,

Li³

et al. 2020

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Purpose This study aimed to explore the potential role and mechanism of garlic-derived S-allylmercaptocysteine (SAMC), the major water-soluble fraction of garlic, in osteoarthritis (OA) both in vivo and in vitro. Methods The effect of SAMC in a surgical-induced OA model was examined by X-ray, staining, ELISA, and immunoblotting. Then the key role of Nrf2 by SAMC treatment in IL-1β stimulated chondrocytes in vitro was determined by gene-knockdown technique. Results SAMC could stabilize the extracellular matrix (ECM) by decreasing metalloproteinase (MMPs) expression to suppress type II collagen degradation in OA rats. The inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, were elevated in OA, which could be down-regulated by SAMC treatment. This effect was parallel with NF-κB signaling inhibition by SAMC. As oxidative stress has been shown to participate in the inflammatory pathways in OA conditions, the key regulator Nrf2 in redox-homeostasis was evaluated in SAMC-treated OA rats. Nrf2 and its down-stream gene NQO-1 were activated in the SAMC-treated group, accompanied by NAD(P)H oxidases 4 (NOX4) expression down-regulated. As a result, the toxic lipid peroxidation byproduct 4-hydroxynonenal (4HNE) was reduced in articular cartilage. In IL-1β-stimulated primary rat chondrocytes, which could mimic OA in vitro, SAMC could ameliorate collagen destruction, inhibit inflammation, and maintain redox-homeostasis. Interestingly, after Nrf2 gene knockdown by adenovirus, the protective effect of SAMC in IL-1β-stimulated chondrocytes disappeared. Conclusion Overall, our study demonstrated that SAMC targeted Nrf2 to protect OA both in vivo and in vitro, which would be a new pharmaceutical way for OA therapy.

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“…TNF-α and IL-1β can promote chondrocytes to release more inflammatory factors, such as nitric oxide (NO), MMPs and ADAMTS. IL-1β can also promote the secretion of TNF-α, which itself exerts effects on IL-1β, promotes the synthesis of MMPs, inhibits the synthesis of proteoglycans and causes cartilage loss [ 61 , 62 ].…”

Section: Cartilage Homeostasismentioning

confidence: 99%