&lt;p&gt;Icariin Alleviates IL-1β-Induced Matrix Degradation By Activating The Nrf2/ARE Pathway In Human Chondrocytes&lt;/p&gt;

Zuo, Shi; Zou, Wei; Wu, Rong-Min; Yang, Jing; Fan, Jiannan; Zhao, Xueke; Li, Haiyang

doi:10.2147/dddt.s203094

Cited by 41 publications

(29 citation statements)

References 52 publications

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“…Paeoniflorin suppresses osteoclast differentiation by controlling the receptor activator of nuclear factor-κ B ligand (RANKL)/osteoprotegerin (OPG) ratio [ 12 ]. Furthermore, icariin and paeoniflorin were also proven to regulate the activity of chondrocytes and inhibit articular cartilage degradation [ 13 , 14 ]. These studies hinted that WB was a promising candidate drug for joint protection in RA patients.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomics‐based analysis of the mechanism by which Wang-Bi capsule alleviates joint destruction in rats with collagen‐induced arthritis

et al. 2021

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Background Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied with joint destruction that often leads to disability. Wang-Bi capsule (WB), a traditional Chinese medicine-based herbs formula, has exhibited inhibition effect on joint destruction of collagen-induced arthritis (CIA) animal model in our previous study. But its molecular mechanisms are still obscure. Methods CIA rats were treated intragastrical with WB for eight weeks, and the effect of joints protection were evaluated by hematoxylin and eosin (H&E) staining, safranin O fast green staining, tartrate-resistant acid phosphatase (TRAP) staining and micro‑CT scanning analysis. The transcriptomic of tarsal joints were used to investigate how WB alleviated joint destruction. Results The histological examination of ankle joints showed WB alleviated both cartilage damage and bone destruction of CIA rats. This protective effect on joints were further evidenced by micro-CT analysis. The transcriptomic analysis showed that WB prominently changed 12 KEGG signaling pathways (“calcium signaling pathway”, “cAMP signaling pathway”, “cell adhesion molecules”, “chemokine signaling pathway”, “complement and coagulation cascades”, “MAPK signaling pathway”, “NF-kappa B signaling pathway”, “osteoclast differentiation”, “PI3K-Akt signaling pathway”, “focal adhesion”, “Gap junction” and “Rap1 signaling pathway”) associated with bone or cartilage. Several genes (including Il6, Tnfsf11, Ffar2, Plg, Tnfrsf11b, Fgf4, Fpr1, Siglec1, Vegfd, Cldn1, Cxcl13, Chad, Arrb2, Fgf9, Egfr) regulating bone resorption, bone formation and cartilage development were identified by further analysis. Meanwhile, these differentially expressed genes were validated by real-time quantitative PCR. Conclusions Overall, the protective effect of WB treatment on joint were confirmed in CIA rats, and its basic molecular mechanisms may be associated with regulating some genes (including Il6, Tnfsf11, Ffar2 and Plg etc.) involved in bone resorption, bone formation and cartilage development.

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Section: Introductionmentioning

confidence: 99%

Transcriptomics‐based analysis of the mechanism by which Wang-Bi capsule alleviates joint destruction in rats with collagen‐induced arthritis

et al. 2021

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“…The role of IL‐1 as a key mediator of cartilage destruction especially in osteoarthritis was described by the early 1990s 9,10,44 . Recent studies have focused on IL‐1 and the IL‐1 receptor as targets for inhibiting and preventing IL‐1 related damage to cartilage and tissues 45–47 . Future study is warranted into whether similar approaches using targeted immunomodulation may be taken to improve fracture healing in infected conditions.…”

Section: Discussionmentioning

confidence: 99%

Locally delivered adjuvant biofilm‐penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection

Cahill

Kwon

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et al. 2021

Journal Orthopaedic Research

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Infection is a devastating complication following an open fracture. We investigated whether local rifampin-loaded hydrogel can combat infection and improve healing in a murine model of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. A transverse fracture was made at the tibia midshaft of C57BL/6J mice aged 10-12 weeks and stabilized with an intramedullary pin. A total of 1 × 10 6 colony-forming units (CFU) of MRSA was inoculated. A collagen-based hydrogel containing low-dose (60 μg) and high-dose (300 μg) rifampin was applied before closure. Postoperative treatment response was assessed through bacterial CFU counts from tissue and hardware, tibial radiographs and microcomputed tomography (μCT), immunohistochemistry, and histological analyses. All untreated MRSA-infected fractures progressed to nonunion by 28 days with profuse MRSA colonization. Infected fractures demonstrated decreased soft callus formation on safranin O stain compared to controls. Areas of dense interleukin-1β stain were associated with poor callus formation. High-dose rifampin hydrogels reduced the average MRSA load in tissue (p < 0.0001) and implants (p = 0.041). Low-dose rifampin hydrogels reduced tissue bacterial load by 50% (p = 0.021). Among sterile models, 88% achieved union compared to 0% of those infected. Mean radiographic union scale in tibia scores improved from 6 to 8.7 with highdose rifampin hydrogel (p = 0.024) and to 10 with combination local/systemic rifampin therapy (p < 0.0001). μCT demonstrated reactive bone formation in MRSA infection. Histology demonstrated restored fracture healing with bacterial elimination. Rifampinloaded hydrogels suppressed osteomyelitis, prevented implant colonization, and improved healing. Systemic rifampin was more effective at eliminating infection and improving fracture healing. Further investigation into rifampin-loaded hydrogels is required to correlate these findings with clinical efficacy.

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“…Icariin has been shown to increase chondrocyte viability by promoting hypoxia-inducible factor-1α expression and anaerobic glycolysis 16,17 and inhibits chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway 18 . Zuo et al demonstrated that icariin alleviated IL-1β-induced matrix degradation and eliminated reactive oxygen species by activating the Nrf2/ARE pathway in human chondrocytes in vitro 19 .…”

Section: Discussionmentioning

confidence: 99%

Icariin interferes with TDP43-induced inflammatory factor secretion and inhibits the JNK and p38 MAPK signaling pathway in vitro

Huang

Zhang

et al. 2021

Arch Med Sci

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IntroductionTo investigate the molecular mechanism of icariin (ICA) intervention in TDP-43 mediated chondrocyte lesions of osteoarthritis.Material and methodsHC-α chondrocytes were transfected with TDP-43 lentiviruses to generate TDP-43-overexpressing chondrocytes and treated with 5 μg/mL icariin. The level of TDP-43, JNK, p38 MAPK and relative factors were detected by Western blotting assays. TNF-α and IL-1β in the supernatant were determined by ELISA.ResultsCompared with the HC-α group, TDP-43 expression was significantly increased in the TDP-43-HC-α group and was not significantly different that of the HC-α+ICA group. However, TDP-43 expression in the TDP-43-HC-α+ICA group was significantly lower than that in the TDP-43-HC-α group. ELISA showed that the secretion of TNF-α and IL-1β in the supernatant of the TDP-43-HC-α group was significantly increased (P<0.01) compared with the HC-α group, but was significantly lower in the supernatant of the TDP-43-HC-α+ICA group than that of the TDP-43-HC-α group (P<0.01). ICA treatment reduced the expression of TDP-43 in chondrocytes and inhibited the elevation of inflammatory cytokines caused by TDP-43. ICA processing can also inhibit the activation of JNK/p38 MAPK related signaling pathways caused by TDP-43. Overexpression of TDP-43 reduced the formation of stress granules (SGs)in chondrocytes, and increased receptor for activated protein kinase C1 (RACK1) level. ICA could reverse these changes.ConclusionsIcariin could interfere with TDP-43-induced secretion of inflammatory factors, inhibit JNK/p38 MAPK signaling. Our findings provided a new theoretical basis for the treatment of osteoarthritis.

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<p>Icariin Alleviates IL-1β-Induced Matrix Degradation By Activating The Nrf2/ARE Pathway In Human Chondrocytes</p>

Cited by 41 publications

References 52 publications

Transcriptomics‐based analysis of the mechanism by which Wang-Bi capsule alleviates joint destruction in rats with collagen‐induced arthritis

Transcriptomics‐based analysis of the mechanism by which Wang-Bi capsule alleviates joint destruction in rats with collagen‐induced arthritis

Locally delivered adjuvant biofilm‐penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection

Icariin interferes with TDP43-induced inflammatory factor secretion and inhibits the JNK and p38 MAPK signaling pathway in vitro

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