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Acupuncture Delays Cartilage Degeneration through Upregulating SIRT1 Expression in Rats with Osteoarthritis |
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Silent mating type information regulation 2 homolog 1 (SIRT1) has been reported to inhibit osteoarthritic gene expression in chondrocytes. |
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Here, efforts in this study were made to unveil the specific role of SIRT1 in the therapy of acupuncture on cartilage degeneration in osteoarthritis (OA). |
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Injection with shSIRT1 sequence-inserted lentiviruses was conducted to investigate the role of SIRT1 in acupuncture-mediated OA. |
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The expressions of SIRT1, cartilage matrix degradation-related proteins (matrix metalloproteinase (MMP)-9 and ADAMTS5), NF-kappaB signaling-related markers (p-p65/p65 and p-IkappaBalpha/IkappaBalpha), and cartilage matrix synthesis-related proteins (collagen II and aggrecan) in the OA cartilage were analyzed by western blot. |
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As a result, acupuncture counteracted OA-associated upregulation of TNF-alpha, IL-2, cartilage matrix degradation-related proteins, and NF-kappaB signaling-related markers, morphological damage, apoptosis, SIRT1 downregulation, and loss of cartilage matrix synthesis-related proteins in rat articular cartilages. |
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SIRT1 silencing reversed acupuncture-induced counteractive effects on the aforementioned OA-associated phenomena (except apoptosis, the experiment regarding which under SIRT1 silencing was not performed). |
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Collectively, acupuncture inhibited chondrocyte apoptosis, inflammation, NF-kappaB signaling activation, and cartilage matrix degradation by upregulating SIRT1 expression to delay OA-associated cartilage degeneration. |
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Acupuncture Reversed OA-Associated Regulation of the Expressions of SIRT1, MMP-9, ADAMTS-5, and the NF-kappaB Signaling Pathway in Rat Articular Cartilages |
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A previous study has documented that overexpression of SIRT1 reversed IL-1beta-induced upregulation of osteoarthritic genes including MMP-9 and ADAMTS5 in human chondrocytes. |
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By western blot, we found that SIRT1 expression level in rat articular cartilages was lower in the Model group than that in the Sham group (P < 0.001), while MMP-9 and ADAMTS5 expression levels of rat articular cartilages in the Model group exceeded those in the Sham group (P < 0.01, P < 0.001; Figure 2(a) and 2(b)). |
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Treatment with acupuncture reversed those OA-associated downregulation of SIRT1 and upregulations of MMP-9 and ADAMTS-5 (P < 0.01, P < 0.001; Figures 2(a) and 2(b)). |
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Acupuncture Inhibited OA-Associated Inflammation, the NF-kappaB Signaling Pathway, and ECM Degradation through Upregulating SIRT1 Expression in Rat Articular Cartilages |
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To investigate SIRT1-associated influences in OA-related gene expressions, we injected lentivirus vectors inserted with shSIRT1 into the affected articular cavity of OA rats. |
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Also, western blot proved that MMP-9 and ADAMTS5 levels were augmented, and SIRT1 level was dwindled in the Model + shSIRT1 group (P < 0.001; Figures 3(c)-3(d)). |