Inflammation and epigenetic regulation in osteoarthritis

Shen, Jie; Abu‐Amer, Yousef; O’Keefe, Regis J.; McAlinden, Audrey

doi:10.1080/03008207.2016.1208655

Cited by 194 publications

(149 citation statements)

References 169 publications

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“…In physiological situations, there is a dynamic balance between ECM synthesis and degradation [11]. The roles of matrix metalloproteinases 13 (MMP13) and an 'aggrecanase' known as a disintegrin and metalloproteinase with thrombospondin motifs − 5 (ADAMTS5), in OA through the degradation of ECM are well established [12][13][14]. It is also clear that type X collagen (COL10A1) is a marker of fibrochondrocyte hypertrophy in meniscus [9,15], and CEBPβ contributes to the pathophysiological process of OA [16,17].…”

Section: Introductionmentioning

confidence: 99%

Substantive molecular and histological changes within the meniscus with tears

Long

Xie

Zhang

et al. 2019

BMC Musculoskelet Disord

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Background: The meniscus plays a vital role in the normal biomechanics of the knee. However, it is not well studied at the molecular level. The purpose of this study was to determine whether molecular and pathological changes in the meniscal tissue vary depending on the presence or absence of meniscal and/or anterior cruciate ligament tear (ACL). Methods: Six normal menisci (group A), seven simple torn menisci (group B) and seven torn menisci with concomitant anterior cruciate ligament tears (group C) were collected. We observed the pathological changes in the menisci and used real-time polymerase chain reaction along with immunohistochemistry and in situ hybridisation to examine the levels of ACAN, ADAMTS5, COL10A1, CEBPβ, MMP13 and miR-381-3p, miR-455-3p, miR-193b-3p, miR-92a-3p, respectively. Patients were scored preoperatively and postoperatively using the Lysholm Knee Scoring Scale and International Knee Documentation Committee Subjective Knee Evaluation Form. Results: Compared with group A, the expression levels of ADAMTS5, COL10A1, CEBPβ, and MMP13 and all the miRNAs were increased while ACAN was down-regulated in groups B and C. Additionally, the gene expression and miRNA levels were higher in group C than that in group B, except for ACAN, which was lower. Several fibrochondrocytes strongly expressed ADAMTS5, CEBPβ, and MMP13 in groups B and C and had high levels of miR-381-3p and miR-455-3p than that in group A. Postoperative Lysholm and IKDC scores were higher in group B than in group C. Conclusions:Our findings suggest that the meniscus tended to degenerate after it was injured, especially when combined with a torn ACL. The miRNAs investigated in this study might also contribute to meniscus degeneration. Patients with a combined injury patterns might have relatively worse joint function.

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Section: Introductionmentioning

confidence: 99%

Substantive molecular and histological changes within the meniscus with tears

Long

Xie

Zhang

et al. 2019

BMC Musculoskelet Disord

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“…Thus, the expression of genes involved in the carbohydrate metabolism and extracellular matrix components were up-regulated. Moreover, chronic low-grade in ammation has also been found contributing to the development and progression of OA [47]. During OA progression, the entire synovial joints were involved in the in ammation process [48].…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Regulators Responsible for Dysregulated Networks in Osteoarthritis by Large-Scale Expression Analysis

Song

Wan

Zhou

et al. 2020

Preprint

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Background: Osteoarthritis (OA) is a worldwide musculoskeletal disorder. However, disease-modifying therapies for OA are not available. Here, we aimed to characterize the molecular signatures of OA and to identify novel therapeutic targets and strategies to improve the treatment of OA.Methods: We collected genome-wide transcriptome data performed on 161 OA and 88 normal human cartilage or synovium tissues from 9 independent datasets. Differential gene expression analysis and functional enrichment were performed to identify genes and pathways that were dysregulated in OA. The computational drug repurposing method was used to uncover drugs that could be repurposed to treat OA.Results: We identified several pathways associated with the development of OA, such as extracellular matrix adhesion, inflammation, carbohydrate metabolism, and collagen organization. By protein-protein interaction (PPI) network analysis, we prioritized several hub genes, such as JUN, IL-6, VAMP8, and SOCS3. Moreover, we repurposed several FDA-approved drugs, such as cardiac glycosides, that could be used in the treatment of OA. Conclusions: We proposed that the hub genes we identified will play a role in cartilage homeostasis and could be important diagnostic and therapeutic targets. Drugs such as protein kinase inhibitors and cardiac glycosides could improve the treatment of OA.

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“…Evidence has shown the important role of in ammation in the pathophysiology of OA [17] . Inhibition of chondrocyte in ammation was a potential therapeutic strategy in OA [18] . In this study, we rst reported that the effects of Sch C on the IL-1β-induced in ammation and cartilage damage by inhibiting MAPK and NF-B signal pathway in SW1353 cells.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of Schisandrin C on chondrocyte damage by inhibiting MAPK and NF-κB signal pathways

Li¹

2020

Preprint

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Background: Osteoarthritis (OA) is a common joint disorder that affects the elderly population. The pathogenesis of OA is related to cartilage degradation and inflammatory response. Schisandrin C (Sch C), a dibenzocyclooctadiene derivative of Schisandra chinensis, has been demonstrated to exert anti-inflammatory effect in various inflammation diseases. However, the effect of Sch C on OA remains unclear. Thus, we aimed to investigate its action on chondrocytes and explore the mechanism associated with the inflammatory response. Methods: In this study, we chose rabbits and SW1353 cells as in vivo/in vitro models. Matrix metalloproteinase (MMP3), Nitric oxide (NO), IL-1β and TNF-α were detected by ELISA kits. The expression of MAPK/NF-κB related signaling molecules were determined by western blot. Results: In vitro, Sch C suppressed the IL-1β-induced production of NO and PGE2. Additionally, Sch C significantly decreased IL-1β-induced p65 phosphorylation and mitogen-activated protein kinase (MAPK) activation, as evidenced by the reduced phosphorylation of p38, extracellular signal-regulated kinase (ERK), and c-Jun amino-terminal kinase (JNK). Moreover, Sch C prevented cartilage damage in rabbit OA model with lower Mankin’s score than the model group. Sch C also inhibited the level of inflammatory cytokines in the articular cavity flushing fluid in rabbit OA model. Conclusions: Our study suggested that Sch C inhibited the IL-1β-induced inflammation and cartilage degradation through suppressing the MAPK and NF-κB signal pathways, indicating a potential in OA treatment.

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Inflammation and epigenetic regulation in osteoarthritis

Cited by 194 publications

References 169 publications

Substantive molecular and histological changes within the meniscus with tears

Substantive molecular and histological changes within the meniscus with tears

Identification of Key Regulators Responsible for Dysregulated Networks in Osteoarthritis by Large-Scale Expression Analysis

Protective effects of Schisandrin C on chondrocyte damage by inhibiting MAPK and NF-κB signal pathways

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