NF-ĸβ upregulates ADAMTS5 expression by direct binding after TNF-α treatment in OUMS-27 chondrosarcoma cell line

Bilgic, Dilek Gun; Hatipoğlu, Ömer Faruk; Cigdem, Sadik; Bilgic, Abdulkadir; Cora, Tulin

doi:10.1007/s11033-020-05514-3

Cited by 5 publications

(5 citation statements)

References 36 publications

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“…They are produced by activated synoviocytes, mononuclear cells, or chondrocytes (22), which have been reported to induce apoptosis in chondrocytes and extracellular matrix (ECM) degradation (23). Moreover, previous studies have confirmed that IL-1β and TNF-α increase the content of ADAMTS-5 to induce KOA, thus, they can be seen as the upstream targets of ADAMTS-5 (5)(6)(7). In our study, we found that CXTB can down regulate IL-1β and TNF-α in a dose-dependent manner, and the trend is consistent with ADAMTS-5.…”

Section: Discussionsupporting

confidence: 87%

“…Previous studies have discovered that a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) can promote the hydrolysis of polysaccharides. Conversely, a recent study showed that interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) are closely related with the destruction of cartilage, and they are involved in the upregulation of ADAMTS-5 (5)(6)(7). Therefore, inhibitors of IL-1β and TNF-α could be promising targets for treating KOA.…”

Section: Introductionmentioning

confidence: 99%

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Cangxitongbi capsule protects articular cartilage of the knee in rats by regulating ADAMTS-5

et al. 2020

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Background: Knee osteoarthritis (KOA) is a disease with a high incidence in elderly patients and traditional Chinese medicine has a significant effect on the treatment of KOA. Cangxitongbi capsule (CXTB) is a traditional Chinese medicine for KOA treatment and has a remarkable curative effect. The purpose of this article is to investigate the mechanism of CXTB in protecting joint cartilage on KOA rats.Methods: A total of 30 male Sprague-Dawley rats were randomly assigned into five groups: control group; model group; low-, mid-, and high-dose CXTB groups (17.5, 35, and 70 mg/mL). KOA models were made by modified Hulth method except the control group. After pharmacological administration for 4 weeks, knee articular cartilages were observed by hematoxylin and eosin (HE) staining and evaluated by Mankin score. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the concentration of ADAMTS-5. The peripheral blood of the rats was collected to detect content of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) by enzyme-linked immunosorbent assay (ELISA). Results:The morphological structure of cartilage in the 3 CXTB groups was significantly improved compared with the model group, and the improvement positively correlated with the drug dosage (P<0.05).Compared with the model group, the expression levels of ADAMTS-5 of the 3 CXTB groups was obviously decreased (P<0.05). Furthermore, the upstream targets of ADAMTS-5, including IL-1β and TNF-α were down-regulated in the 3 CXTB groups (P<0.05).Conclusions: Knee joint cartilage on KOA model rats is protected by CXTB via down-regulation of ADAMTS-5. The upstream targets of ADAMTS-5, IL-1β and TNF-α, were also down-regulated by CXTB.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Cangxitongbi capsule protects articular cartilage of the knee in rats by regulating ADAMTS-5

et al. 2020

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“…IL-1β and TNF-α, which can suppress ECM synthesis and promote apoptosis, are considered to be representative pro-inflammatory factors and catabolic markers of OA [ 24 ]. Previous studies have confirmed that IL-1β and TNF-α can be used as upstream targets of MMP13 and ADAMTS5 to induce OA [ 25 , 26 ]. Therefore, the inhibitory effect of osthole on IL-1β and TNF-α was examined in this study, which further revealed the anti-KOA function of osthole.…”

Section: Discussionmentioning

confidence: 94%

Osthole Suppresses Knee Osteoarthritis Development by Enhancing Autophagy Activated via the AMPK/ULK1 Pathway

Wang

et al. 2022

Molecules

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Knee osteoarthritis (KOA) is an increasingly prevalent heterogeneous disease characterized by cartilage erosion and inflammation. As the main chemical constituent of Angelicae Pubescentis Radix (APR), an anti-inflammatory herbal medicine, the potential biological effects and underlying mechanism of osthole on chondrocytes and KOA progression remain elusive. In this study, the potential effect and mechanism of osthole on KOA were investigated in vitro and in vivo. We found that osthole inhibited IL-1β-induced apoptosis and cartilage matrix degeneration by activating autophagy in rat chondrocytes. In addition, osthole could activate autophagy through phosphorylation of AMPK/ULK1, and AMPK serves as a positive upstream regulator of ULK1. Furthermore, KOA rats treated with osthole showed phosphorylation of the AMPK/ULK1 pathway and autophagy activation, as well as cartilage protection. Collectively, the AMPK/ULK1 signaling pathway can be activated by osthole to enhance autophagy, thereby suppressing KOA development. Osthole may be a novel and effective therapeutic agent for the clinical treatment of KOA.

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“…Go and KEGG analyzes suggested that DEGs were involved in regulating NF-κB signaling pathway. NF-κB signaling pathway is related to the progression of OA and can induce chondrocyte apoptosis and inflammation [ 19 ]. Accordingly, we investigated the regulatory mechanism of OSTF1 on NF-κB signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, these inflammatory factors can combine with receptors on the articular cartilage surface to activate the NF-κB pathway in chondrocytes [ 18 ]. NF-κB signaling pathway plays a crucial role in inflammatory response, which may contribute to chondrocyte cell death and cartilage destruction [ 19 ]. However, whether OSTF1 affects OA process by regulating the NF-κB signaling pathway needs further verification.…”

Section: Introductionmentioning

confidence: 99%

OSTF1 knockdown mitigates IL-1β-induced chondrocyte injury via inhibiting the NF-κB signaling pathway

Hu,

2024

Heliyon

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NF-ĸβ upregulates ADAMTS5 expression by direct binding after TNF-α treatment in OUMS-27 chondrosarcoma cell line

Cited by 5 publications

References 36 publications

Cangxitongbi capsule protects articular cartilage of the knee in rats by regulating ADAMTS-5

Cangxitongbi capsule protects articular cartilage of the knee in rats by regulating ADAMTS-5

Osthole Suppresses Knee Osteoarthritis Development by Enhancing Autophagy Activated via the AMPK/ULK1 Pathway

OSTF1 knockdown mitigates IL-1β-induced chondrocyte injury via inhibiting the NF-κB signaling pathway

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