Scutellarin suppresses cartilage destruction in osteoarthritis mouse model by inhibiting the NF-κB and PI3K/AKT signaling pathways

Wang, Wenhan; Li, Jiayi; Li, Feng; Peng, Jiangfan; Xu, Mingyang; Shangguan, Yangtao; Li, Yuanming; Zhao, Yunpeng; Qiu, Cheng; Qu, Ruize; Li, Weiwei; Zhang, Cuijuan; Zhang, Tingguo

doi:10.1016/j.intimp.2019.105928

Cited by 22 publications

(16 citation statements)

References 31 publications

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“…In this study, we identified 20 genes that were differentially expressed between OA and normal samples and common to all five selected GEO mRNA expression datasets. Through GO and KEGG enrichment analyses, we determined that the processes affected by these genes were consistent with the findings of previous studies in which these pathways were identified as contributors to the pathological process of OA [28][29][30]. We also constructed PPI networks containing these DEGs.…”

Section: Discussionsupporting

confidence: 81%

Identification of a potential gene target for osteoarthritis based on bioinformatics analyses

Duan

et al. 2020

J Orthop Surg Res

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Background: Osteoarthritis (OA) is the most common chronic joint disease worldwide. It is characterized by pain and limited mobility in the affected joints and may even cause disability. Effective clinical options for its prevention and treatment are still unavailable. This study aimed to identify differences in gene signatures between tissue samples from OA and normal knee joints and to explore potential gene targets for OA. Methods: Five gene datasets, namely GSE55457, GSE55235, GSE12021, GSE10575, and GSE1919, were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the R programming software. The functions of these DEGs were analyzed, and a protein-protein interaction (PPI) network was constructed. Subsequently, the most relevant biomarker genes were screened using a receiver operating characteristic (ROC) curve analysis. Finally, the expression of the protein encoded by the core gene PTHLH was evaluated in clinical samples. Results: Eleven upregulated and 9 downregulated DEGs were shared between the five gene expression datasets. Based on the PPI network and the ROC curves of upregulated genes, PTHLH was identified as the most relevant gene for OA and was selected for further validation. Immunohistochemistry confirmed significantly higher PTHLH expression in OA tissues than in normal tissues. Moreover, similar PTHLH levels were detected in the plasma and knee synovial fluid of OA patients. Conclusion: The bioinformatics analysis and preliminary experimental verification performed in this study identified PTHLH as a potential target for the treatment of OA.

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Section: Discussionsupporting

confidence: 81%

Identification of a potential gene target for osteoarthritis based on bioinformatics analyses

Duan

et al. 2020

J Orthop Surg Res

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“…As we know, NF-kB signaling pathway was the key link of Hypoxia-inducible factor-1, NOD-like receptors and TNF-α induced OA progression [34,36,37]. NF-kB signaling pathway was also the key target of the several anti-osteoarthritis compounds, including Scutellarin [11,38,39]. However, the action mode of Scutellarin on NF-kB signaling pathway was still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Scutellarin (SCU) (4′,5,6-trihydroxy avonoid-7-glucuronide), a avonoid glycoside isolated from Erigeron breviscapus, exhibits anti-in ammatory, anti-oxidative, and anti-apoptotic activity in various pathological processes, including cerebrovascular disease, dermatitis, atherosclerosis, and myocardial infarction [8][9][10]. Recently, several studies have showed Scutellarin exerted inhibitive effects on the OA [11][12][13]. The underlying anti-OA mechanisms played by Scutellarin are closely related with several biological signal pathways, including Nrf2 pathway, Wnt/β-catenin pathway, MAPK pathway, NF-κB pathway and PI3K/AKT pathway [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, several studies have showed Scutellarin exerted inhibitive effects on the OA [11][12][13]. The underlying anti-OA mechanisms played by Scutellarin are closely related with several biological signal pathways, including Nrf2 pathway, Wnt/β-catenin pathway, MAPK pathway, NF-κB pathway and PI3K/AKT pathway [11][12][13]. However, the detailed mechanisms of scutellarin against OA remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Systematic elucidation of the molecular mechanism of scutellarin against osteoarthritis based on network pharmacology

Guo

Zhang

Sun

2020

Preprint

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Background Scutellarin was reported to exerted inhibitive effects on osteoarthritis, However, the detailed mechanisms remain unclear. In this study, we investigated underlying multi-target mechanisms of scutellarin against osteoarthritis by using network pharmacology analysis and molecular docking. Results Scutellarin exerted inhibitive effects on osteoarthritis by regulating the function of several new signaling pathways, such as TNF signaling pathway, NOD-like receptor signaling pathway and HIF-1 signaling pathway. Molecular docking analysis showed there was better interaction between scutellarin and several NF-kB signaling proteins, including NFKBIA, RELA and NFKB1. In addition, the results showed Pi-cation, Pi-donor-hydrogen and Pi-alkyl were the main forms of interaction between scutellarin and NFKB1 and NFKBIA, Pi-Pi T-shaped, Pi-alkyl and hydrogen bonding were the main forms of interaction between scutellarin and RELA. Conclusion Taken together, TNF signaling pathway, NOD-like receptor signaling pathway and HIF-1 signaling pathway were possible signaling pathways, NFKBIA, RELA and NFKB1were possible targets associated with the activities of scutellarin against osteoarthritis. However, it is imperative that these targets should be thoroughly verified by in vitro and in vivo experiments.

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“…A large number of studies have confirmed that the development of OA is regulated by multiple signaling pathways such as Wnt/ β -catenin [ 14 ], PI3K/AKT [ 15 ], and Nuclear factor-kappa B (NF- κ B) signaling pathways [ 16 ]. Several studies have shown that the abnormal and continuous activation of NF- κ B signaling pathway is related to osteoarthritis.…”

Section: Introductionmentioning

confidence: 99%

Platelet-Rich Plasma Combined with Alendronate Reduces Pain and Inflammation in Induced Osteoarthritis in Rats by Inhibiting the Nuclear Factor-Kappa B Signaling Pathway

Xin

Wang

Yuan

et al. 2020

BioMed Research International

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Purpose. Osteoarthritis (OA) is one of the common degenerative diseases of the joint in the world. This study was designed to explore the effect of platelet-rich plasma (PRP) combined with alendronate (ALN) on OA. Methods. We induced OA model by anterior cruciate ligament transection (ACLT) method in rats and treating chondrocytes by IL-1β in vitro. PRP and/or ALN were used to treat induced rats and chondrocytes. Hematoxylin and eosin (H&E) and Safranin O staining were used to observe the structures of cartilage. The mRNA expression of Collagen II, MMP-13, and inflammatory factors (IL-18, IL-1β, and TNF-α) in the cartilage and chondrocytes of rats was determined by qRT-PCR. The expression of NF-κB pathway-related proteins (p-p65, p65, IκBα, and p-IκBα) in the cartilage and chondrocytes of rats was determined by Western blot. The proliferation of chondrocytes was detected by MTT assay. Results. Treatment with PRP, ALN, or PRP combined with ALN decreased the degree of cartilage destruction, the mRNA expression of MMP-13 and inflammatory factors (IL-18, IL-1β, and TNF-α), and the protein expression of p-IκBα/IκBα and p-p65/p65, increased Collagen II expression, and the threshold of tender and thermal pain in OA rats. Meanwhile, ALN, PRP, or ALN combined with PRP reversed the inhibiting effect of phorbol myristate acetate (PMA, an NF-κB agonist) on cell proliferation and cartilage matrix metabolism. Among them, the effects of ALN combined with PRP were most obvious. Conclusion. PRP combined with ALN delayed OA progression by inhibiting the NF-κB signaling pathway.

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Scutellarin suppresses cartilage destruction in osteoarthritis mouse model by inhibiting the NF-κB and PI3K/AKT signaling pathways

Cited by 22 publications

References 31 publications

Identification of a potential gene target for osteoarthritis based on bioinformatics analyses

Identification of a potential gene target for osteoarthritis based on bioinformatics analyses

Systematic elucidation of the molecular mechanism of scutellarin against osteoarthritis based on network pharmacology

Platelet-Rich Plasma Combined with Alendronate Reduces Pain and Inflammation in Induced Osteoarthritis in Rats by Inhibiting the Nuclear Factor-Kappa B Signaling Pathway

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