Mummy Prevents IL-1β-Induced Inflammatory Responses and Cartilage Matrix Degradation via Inhibition of NF-қB Subunits Gene Expression in Pellet Culture System

Morrovati, F; N, Karimian Fathi; J, Soleimani Rad; Montaseri, Azadeh

doi:10.15171/apb.2018.033

Cited by 7 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-1β is member of Interlukin family, it can cause various pathogenic changes in chondrocytes as it is found to play important role in progression if osteoarthritis. 21 , 22 In the present work it was found that expression of miR-152 was suppressed in IL-1β exposed normal chondrocytes. Also it was found that; upregulation of miR-152 expression caused a significant inhibition of IL-1β mediated apoptosis in chondrocytes.…”

Section: Discussionsupporting

confidence: 58%

miR-152 Attenuates Apoptosis in Chondrocytes and Degeneration of Cartilages in Osteoarthritis Rats via TCF-4 Pathway

Wan

et al. 2020

Dose-Response

View full text Add to dashboard Cite

Introduction: Osteoarthritis (OA) is associated with deregulation of various miRNAs (miRs). The present study reported protective effect of miR-152 in osteoarthritis. Methods: Tissue cartilage tissues of OA and normal subjects were used, rat model of anterior cruciate ligament transection (ACLT) was developed. Cartilage study was done by Safranin O-fast green, histological and immunostaining. The chondrocytes were isolated from tissues and were treated with IL-1β and infected with miR-152 or TCF-4 cloned lentiviral vectors. MTT assay was done for cell viability, apoptosis by Annexin-V-FITC staining. Expressions of proteins by western blot assay. Collagen-II assay was done by immunofluroscent assay. Luciferase activity by dual luciferase reporter assay. Results: Upregulation of miR-152 improved viability of chondrocytes, decreased apoptosis and balanced the catabolic and anabolic factors of extracellular matrix in vitro. Injecting miR-152 lentivirus in rats improved articular cartilage in osteoarthritis ACLT rats. Bioinformatics analysis suggested TCF-4 as favorable target gene of miR-152, having binding site on the 3’UTR region of TCF-4 mRNA and inhibited the expression of TCF-4. Osteoarthritis tissue cartilage both from humans and rats showed expression of miR-152 inversely linked with expression of TCF-4. Conclusion: Present study concludes miR-152 diminished the progression of osteoarthritis partially by inhibiting the expression of TCF-4.

show abstract

Section: Discussionsupporting

confidence: 58%

miR-152 Attenuates Apoptosis in Chondrocytes and Degeneration of Cartilages in Osteoarthritis Rats via TCF-4 Pathway

Wan

et al. 2020

Dose-Response

View full text Add to dashboard Cite

show abstract

“…REL, also termed C-Rel, is a subunit of NF-κB, and it is well established that NF-κB serves a key role in OA (59). Morrovati et al (60) demonstrated that treatment of chondrocytes with IL-1β resulted in a significant increase in the expression level of C-Rel. However, there is still uncertainty as to whether C-Rel may serve as a therapeutic target for OA.…”

Section: Discussionmentioning

confidence: 99%

Identification of key gene modules and transcription factors for human osteoarthritis by weighted gene co‑expression network analysis

Gao

Sun

2019

Exp Ther Med

View full text Add to dashboard Cite

Osteoarthritis (OA) is one of the most prevalent causes of joint disease. However, the pathological mechanisms of OA have remained to be completely elucidated, and further investigation into the underlying mechanisms of OA development and the identification of novel therapeutic targets are urgently required. In the present study, the dataset GSE114007 was downloaded from the Gene Expression Omnibus database. Based on weighted gene co-expression network analysis (WGCNA) and the identification of differentially expressed genes (DEGs), the microarray data were further analyzed to identify hub genes, key transcription factors (TFs) and pivotal signaling pathways involved in the pathogenesis of OA. A total of 1,898 genes were identified to be differentially expressed between OA samples and normal samples. Based on WGCNA, the present study identified 5 hub modules closely associated with OA, and the potential key TFs for hub modules were further explored based on CisTargetX. The results demonstrated that B-Cell Lymphoma 6, Myelin Gene Expression Factor 2, Activating Transcription Factor 3, CCAAT Enhancer Binding Protein γ, Nuclear Factor Interleukin-3-Regulated, FOS Like Antigen-2, FOS-Like Antigen-1, Fos Proto-Oncogene, JunD Proto-Oncogene, Transcription Factor CP2 Like 1, RELA proto-oncogene NF-kB subunit, SRY-box transcription factor 3, V-Ets Avian Erythroblastosis Virus E26 Oncogene Homolog 2, Interferon Regulatory Factor 4 and REL proto-oncogene, NF-kB subunit were the potential key TFs. In addition, osteoclast differentiation, FoxO, MAPK and PI3K/Akt signaling pathways were revealed to be imperative for the pathogenesis of OA, as these 4 pivotal signaling pathways were observed to be tightly linked through 4 key TFs Fos Proto-Oncogene, JUN, JunD Proto-Oncogene and MYC, and 4 DEGs Vascular Endothelial Growth Factor A, Growth Arrest and DNA Damage Inducible α, Growth Arrest and DNA Damage Inducible β and Cyclin D1. The present study identified a set of potential key genes and signaling pathways, and provided an important opportunity to advance the current understanding of OA.

show abstract

“…Therefore, we explored the effects of IL-1β on the expression of aggrecan, collagen type II, aggrecanases, ADAMTS-4, and ADAMTS-5. Based on previous studies, the expression of MMP-13 was selected as the biomarker, which has recently been proven to be strongly upregulated in IL-1β-induced cartilage matrix degradation 18. As expected, IL-1β treatment significantly increased the MMP13 protein levels and decreased the collagen type II and aggrecan levels (Figure 1A).…”

Section: Resultsmentioning

confidence: 71%

<p>Desumoylation of aggrecan and collagen II facilitates degradation via aggrecanases in IL-1β-mediated osteoarthritis</p>

Zhu

Cui

Zhang

et al. 2019

JPR

View full text Add to dashboard Cite

Background: Aggrecan plays a crucial role in the ability of tissues to withstand compressive loads during the pathological progression of osteoarthritis (OA). Progressive loss of aggrecan from cartilage may result in exposure of the collagen matrix and can lead to its disintegration by metalloproteases. Although aggrecanases are expressed constitutively in human chondrocytes, the degradation of aggrecan is induced by proinflammatory cytokines; however, little is known about the underlying mechanisms. Methods: Human primary chondrocytes from OA patients or healthy donors and human chondrogenic SW1353 cells were cultured and stimulated with IL-1β in vitro, the mRNA expressions and protein levels of MMP-13, ADAMTS-4, ADAMTS-5, SENP1, and SENP2 were determined using real time PCR and Western blot, respectively. The localizations of aggrecan and Col-II, as well as the SUMOylation modification of these proteins were analyzed using immunofluorescence and immunoprecipitation assays, respectively. Results: Our results showed that a proinflammatory cytokine interleukin-1β induced the OA model and desumoylation of aggrecan and collagen type II because the small ubiquitin-like modifier 2/3 (SUMO2/3) was co-localized with aggrecan and collagen type II proteins and interacted physically with them. Mechanistic studies have shown that knockdown of SUMO2/3 expression can significantly enhance the rate of degradation of aggrecan and collagen type II at both the mRNA and protein levels in the OA model. In addition, SUMO-specific protease 2 (SENP2) plays important roles in the desumoylation of aggrecan, while knockdown of SENP2 can protect aggrecan and collagen type II. Clinical assays have shown that OA patients have higher SENP2 levels than healthy controls, and the SENP2 level correlates negatively with both aggrecan and collagen type II levels. Conclusion: SENP2 desumoylates aggrecan and collagen type II proteins in the inflammation induced OA, and SENP2 expression correlates with OA progression.

show abstract

Mummy Prevents IL-1β-Induced Inflammatory Responses and Cartilage Matrix Degradation via Inhibition of NF-қB Subunits Gene Expression in Pellet Culture System

Cited by 7 publications

References 21 publications

miR-152 Attenuates Apoptosis in Chondrocytes and Degeneration of Cartilages in Osteoarthritis Rats via TCF-4 Pathway

miR-152 Attenuates Apoptosis in Chondrocytes and Degeneration of Cartilages in Osteoarthritis Rats via TCF-4 Pathway

Identification of key gene modules and transcription factors for human osteoarthritis by weighted gene co‑expression network analysis

<p>Desumoylation of aggrecan and collagen II facilitates degradation via aggrecanases in IL-1β-mediated osteoarthritis</p>

Contact Info

Product

Resources

About