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BACKGROUND: Angiogenesis is involved in the progression of early-stage knee osteoarthritis. Synovium, cartilage and subchondral bone all have pathological manifestations of angiogenesis. To explore the inhibitory ability and related pathways of ligustrazine and overexpression of miR-20b-5p on pathological angiogenesis in these tissues will help to develop new drugs for the treatment of early-stage knee osteoarthritis. OBJECTIVE: To investigate the effects of ligustrazine and overexpression of miR-20b-5p on synovial, cartilage and subchondral bone angiogenesis in rats with early-stage knee osteoarthritis. METHODS: Twenty-five Sprague-Dawley rats were randomly divided into five groups (n=5 per group): model group, agomir NC group, agomir group, ligustrazine+agomir NC group, and ligustrazine+agomir group. The rats in the agomir group and ligustrazine+agomir group were intraarticularly injected with miR-20b-5p agomir solution, while the rats in the agomir NC group and ligustrazine+agomir NC group were intraarticularly injected with the same dose of miR-20b-5p agomir NC solution. The model group was injected with the same amount of normal saline intraarticularly and intragastrically. The rats in the ligustrazine+agomir group and ligustrazine+agomir NC group were also given intragastric administration of ligustrazine. Intraarticular administration was done only once and intragastric administration was performed once a day for 4 weeks. Four weeks later, the rats in each group were killed and the left knee joint was fixed and made into paraffin sections for hematoxylin-eosin staining, Safranin O-fast green staining, and immunohistochemical staining. RESULTS AND CONCLUSION: In synovial tissue, the vascular density, inflammatory cell infiltration, vascular endothelial growth factor protein and Notch1 protein in the agomir group, ligustrazine+agomir NC group and ligustrazine+agomir group were significantly lower than those in the model group and agomir NC group (P < 0.05). The vascular density, inflammatory cell infiltration, vascular endothelial growth factor protein and Notch1 protein in the ligustrazine+agomir group were significantly lower than those in the agomir group and ligustrazine+agomir NC group (P < 0.05). In cartilage and subchondral bone tissues, the loss of cartilage matrix and vascular invasion in the agomir group, ligustrazine+agomir NC group and ligustrazine+agomir group were slighter than those in the model group and agomir NC group. In cartilage and subchondral bone tissues, Osteoarthritis Research Society International score, vascular endothelial growth factor protein and Notch1 protein in the agomir group, ligustrazine+agomir NC group and ligustrazine+agomir group were significantly lower than those in the model group and agomir NC group (P < 0.05). Osteoarthritis Research Society International score, vascular endothelial growth factor protein and Notch1 protein expression in the ligustrazine+agomir group were significantly lower than those in the agomir group and ligustrazine+agomir NC group (P < 0.05). To conclude, ligustrazine and overexpression of miR-20b-5p in synovium, cartilage and subchondral bone may inhibit vascular endothelial growth factor/Notch1 mediated angiogenesis, improve various histological manifestations to some extent, and alleviate disease progression in rats with earlystage knee osteoarthritis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bushen Jianpi Huoxue Recipe is an empirical prescription commonly used in the treatment of osteoporosis. However, its potential molecular mechanism needs to be further explored. OBJECTIVE: To explore the potential molecular mechanism of Bushen Jianpi Huoxue Recipe in the treatment of osteoporosis based on network pharmacology, and to verify the possibility of its effect through histone methylation modification. METHODS: Based on the network pharmacology, the active drug components and action targets of Bushen Jianpi Huoxue Recipe were screened from relevant database using relevant software, and the targets of osteoporosis-related diseases were obtained. The intersected targets were obtained and identified as the potential targets of Bushen Jianpi Huoxue Recipe in the treatment of osteoporosis. The drug component-target network was constructed by String and Cytoscape software, and the core targets were screened out. The functions and genes related to histone modification were extracted based on the results of GO biological analysis, and the target genes related to histone modification were screened from the core targets. Literature analysis was performed to indicate the possible biological role of target genes in osteoporosis and histone modification. In vitro cell experiments were conducted to verify the effect of Bushen Jianpi Huoxue Recipe on osteogenic differentiation in the treatment of osteoporosis via the regulation of histone demethylase JMJD2B that is closely related to the target. RESULTS AND CONCLUSION: A total of 118 active drug components related to osteoporosis were identified, with 165 corresponding targets. The core targets were IL6, TP53, FOS, JUN, STAT3, RELA, CCND1, MYC, MAPK1, MAPK8, MAPK14, VEGFA, AKT1, ESR1, TNF, NR3C1 and so on. GO biological function analysis showed that the biological functions such as drug response, nutrition level response, oxidative stress response, steroid hormone response, transcriptional regulation, transcription factor binding, phosphatase binding, protease binding, and steroid hormone receptor activity were closely related to the common targets. The core targets such as MAPK8, VEGFA and TP53 were related to histone modification; luteolin, quercetin, and kaempferol might be the main drug components affecting histone modification in the treatment of osteoporosis. Results from the in vitro cell experiment revealed that the expression of osteogenesis-related alkaline phosphatase, JMJD2B and RUNX2 protein increased significantly in rat bone marrow mesenchymal stem cells treated with Bushen Jianpi Huoxue Recipe. Histone demethylase JMJD2B, which is closely related to the pharmacological target of Bushen Jianpi Huoxue Recipe, might promote osteogenic differentiation in the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: Studies have reported that the combined use of ginger extract to reduce the levels of serum pro-inflammatory cytokines, including interleukin- 1β, interleukin-6, tumor necrosis factor-α, is related to the reduction of cartilage injury in knee osteoarthritis. OBJECTIVE: To observe the protective effect of red ginger extract on articular cartilage and the expression of serum interleukin-1β, interleukin-6, tumor necrosis factor-α and cartilage tissue type II collagen α1 mRNA in rats with early knee osteoarthritis, and to explore the protective effect of red ginger extract on articular cartilage of rats with early knee osteoarthritis and its possible mechanism. METHODS: Fifty SPF Sprague-Dawley rats were randomly divided into blank group, model group, low-dose red ginger, high-dose red ginger and positive control group (n=10 per group). Except for the blank group, the rats in the other four groups were used to prepare knee osteoarthritis models by intraarticular injection of 4% papain 0.2 mL+0.03 mol/L L-cysteine mixed solution. The rats in the blank and model groups were fed routinely, and the lowdose red ginger, high-dose red ginger and positive control groups were given 50 mg/kg red ginger extract aqueous solution, 100 mg/kg red ginger extract aqueous solution and 18 mg/kg celecoxib capsule aqueous solution respectively. All the interventions were conducted once a day, for 4 continuous weeks. Four weeks after treatment, the rats in each group were killed and the knee joints were stained with safranin O-fast green. The articular cartilage was scored by Mankin scoring. The expression levels of interleukin-1β, interleukin-6, tumor necrosis factor-α in serum and type II collagen α1 mRNA in cartilage were detected. The study protocol was approved by the Animal Ethics Committee of Guangzhou University of Chinese Medicine, with an approval No. 20190917002. RESULTS AND CONCLUSION: The pathological section of knee cartilage showed that there was cartilage matrix loss in the model and each treatment group, and the Mankin score of each treatment group was significantly higher than that of the blank group (P < 0.05) and lower than that of the model group (P < 0.05). There was no significant difference between the high-dose group and the positive control group (P > 0.05), but the scores of the two groups were lower than that of the low-dose group. The levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were upregulated in the positive control group, high-dose red ginger group and low-dose red ginger group compared with the blank group and down-regulated compared with the model group (P < 0.05). Moreover, and the levels of these cytokines were ranked as follows: positive control group < high-dose red ginger group < low-dose red ginger group (P < 0.05). The level of type II collagen α1 mRNA in cartilage showed no significant difference between the blank group and the high-dose red ginger group and the positive control group (P > 0.05), whereas the expression of type II collagen α1 mRNA was significantly increased in the model group and low-dose red ginger group compared with the other three groups (P < 0.05). To conclude, red ginger extract may protect the articular cartilage of knee osteoarthritis by inhibiting interleukin-1β, interleukin-6, and tumor necrosis factor-α, thereby delaying the development of knee osteoarthritis. Compared with the low-dose group, high-dose red ginger extract has better anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

Copyright of Natural Gas Industry is the property of Natural Gas Industry Journal Agency and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)