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      Danshensu inhibits the IL-1β-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway

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          Abstract

          Purpose

          Osteoarthritis (OA) is the most common inflammatory disease associated with pain and cartilage destruction. Interleukin (IL)-1β is widely used to induce inflammatory response in OA models. This study aimed to explore the role of Danshensu (DSS) in IL-1β-induced inflammatory responses in OA.

          Methods

          IL-1β was used to induce chondrocyte inflammation. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. IL-6, COX-2, TNF-α, and iNOS mRNA levels were detected by qRT-PCR. MMP3, MMP13, ADAMTS4, ADAMTS5, Aggrecan, Collagen, p-IκBα, and p-p65 protein levels were detected by Western blot. An OA mouse model was established by surgical destabilization of the medial meniscus (DMM), and the Osteoarthritis Research Society International (OARSI) score was evaluated by H&E staining.

          Results

          DSS did not affect the levels of inflammatory indicators including IL-6, COX-2, TNF-α, iNOS, PEG2, and NO but suppressed COX-2 and iNOS protein expression in IL-1β treated chondrocytes. In addition, DSS downregulated IL-1β-enhanced expression of MMP3, MMP13, ADAMTS4, and ADAMTS5 and upregulated aggrecan and collagen expression. Moreover, DSS significantly inhibited IL-1β-induced phosphorylation of p-IκBα and p-p65 in a dose-dependent manner in chondrocytes, suggesting it plays a role in the NF-κB signaling pathway. Furthermore, DSS significantly reduced DMM-induced cartilage OARSI score in mice, further demonstrating its protective role in OA progression in vivo.

          Conclusions

          Our study revealed the protective role of DSS in OA, suggesting that DSS might act as a potential treatment for OA.

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          Most cited references40

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          Analyzing real-time PCR data by the comparative C(T) method.

          Two different methods of presenting quantitative gene expression exist: absolute and relative quantification. Absolute quantification calculates the copy number of the gene usually by relating the PCR signal to a standard curve. Relative gene expression presents the data of the gene of interest relative to some calibrator or internal control gene. A widely used method to present relative gene expression is the comparative C(T) method also referred to as the 2 (-DeltaDeltaC(T)) method. This protocol provides an overview of the comparative C(T) method for quantitative gene expression studies. Also presented here are various examples to present quantitative gene expression data using this method.
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            Osteoarthritis cartilage histopathology: grading and staging.

            Current osteoarthritis (OA) histopathology assessment methods have difficulties in their utility for early disease, as well as their reproducibility and validity. Our objective was to devise a more useful method to assess OA histopathology that would have wide application for clinical and experimental OA assessment and would become recognized as the standard method. An OARSI Working Group deliberated on principles, standards and features for an OA cartilage pathology assessment system. Using current knowledge of the pathophysiology of OA morphologic features, a proposed system was presented at OARSI 2000. Subsequently, this was widely circulated for comments amongst experts in OA pathology. An OA cartilage pathology assessment system based on six grades, which reflect depth of the lesion and four stages reflecting extent of OA over the joint surface was developed. The OARSI cartilage OA histopathology grading system appears consistent and simple to apply. Further studies are required to confirm the system's utility.
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              Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk.

              In diarthrodial joints, the articular cartilage, calcified cartilage, and subchondral cortical and trabecular bone form a biocomposite - referred to as the osteochondral unit - that is uniquely adapted to the transfer of load. During the evolution of the osteoarthritic process the compositions, functional properties, and structures of these tissues undergo marked alterations. Although pathological processes might selectively target a single joint tissue, ultimately all of the components of the osteochondral unit will be affected because of their intimate association, and thus the biological and physical crosstalk among them is of great importance. The development of targeted therapies against the osteoarthritic processes in cartilage or bone will, therefore, require an understanding of the state of these joint tissues at the time of the intervention. Importantly, these interventions will not be successful unless they are applied at the early stages of disease before considerable structural and functional alterations occur in the osteochondral unit. This Review describes the changes that occur in bone and cartilage during the osteoarthritic process, and highlights strategies for how this knowledge could be applied to develop new therapeutic interventions for osteoarthritis.
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                Author and article information

                Contributors
                FengChenmedicine@163.com
                uj1889@163.com
                Journal
                Mol Med
                Mol Med
                Molecular Medicine
                BioMed Central (London )
                1076-1551
                1528-3658
                20 July 2021
                20 July 2021
                2021
                : 27
                : 80
                Affiliations
                [1 ]GRID grid.256112.3, ISNI 0000 0004 1797 9307, Shengli Clinical Medical College of Fujian Medical University, ; Fuzhou, 350004 Fujian Province People’s Republic of China
                [2 ]GRID grid.415108.9, ISNI 0000 0004 1757 9178, Department of Emergency Surgery, , Fujian Provincial Hospital, ; No.134 East Street, Gulou District, Fuzhou, 350001 Fujian Province People’s Republic of China
                [3 ]GRID grid.415108.9, ISNI 0000 0004 1757 9178, Fujian Provincial Key Laboratory of Emergency Medicine, , Fujian Provincial Hospital, ; Fuzhou, 350001 Fujian People’s Republic of China
                Author information
                http://orcid.org/0000-0002-0313-5176
                Article
                329
                10.1186/s10020-021-00329-9
                8290616
                34284715
                da5fe997-a664-434e-a96d-ac375a40f678
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 December 2020
                : 15 June 2021
                Funding
                Funded by: The Youth Scientific Research Project of Fujian Provincial Health Commission
                Award ID: 2012-2-5
                Funded by: Excellent Youth Project of Fujian Provincial Hospital
                Award ID: 2014068
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                osteoarthritis,danshensu,il-1β,inflammatory response,nf-κb

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