Icariin inhibits MMP-1, MMP-3 and MMP-13 expression through MAPK pathways in IL-1β-stimulated SW1353 chondrosarcoma cells

Zeng, Li; Rong, Xiaofeng; Li, Rongheng; Wu, Xingye

doi:10.3892/mmr.2017.6312

Cited by 44 publications

(36 citation statements)

References 22 publications

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“…It has been reported that the IL-1β-induced increase in MMP-13 expression requires p38 activity, JNK activity, and NF-κB translocation but does not involve MEK, whereas the increase in MMP-1 expression requires p38 and MEK activity but does not involve JNK and NF-κB [79]. MMP-1 and MMP-3 expression in IL-1β-stimulated chondrosarcoma cells was suppressed by p38 and ERK inhibitors but not by JNK inhibitor, and MMP-13 expression was suppressed by p38 and JNK inhibitors but not ERK inhibitor [80]. These findings indicate that the signaling pathway for IL-1β-mediated regulation of MMP-13 is different from that for IL-1β-mediated regulation of MMP-1 and MMP-3 and may not involve MEK/ERK activities.…”

Section: Discussionmentioning

confidence: 90%

High-Frequency Near-Infrared Diode Laser Irradiation Attenuates IL-1β-Induced Expression of Inflammatory Cytokines and Matrix Metalloproteinases in Human Primary Chondrocytes

Sakata

Kunimatsu

Tsuka

et al. 2020

JCM

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High-frequency near-infrared diode laser provides a high-peak output, low-heat accumulation, and efficient biostimulation. Although these characteristics are considered suitable for osteoarthritis (OA) treatment, the effect of high-frequency near-infrared diode laser irradiation in in vitro or in vivo OA models has not yet been reported. Therefore, we aimed to assess the biological effects of high-frequency near-infrared diode laser irradiation on IL-1β-induced chondrocyte inflammation in an in vitro OA model. Normal Human Articular Chondrocyte-Knee (NHAC-Kn) cells were stimulated with human recombinant IL-1β and irradiated with a high-frequency near-infrared diode laser (910 nm, 4 or 8 J/cm2). The mRNA and protein expression of relevant inflammation- and cartilage destruction-related proteins was analyzed. Interleukin (IL) -1β treatment significantly increased the mRNA levels of IL-1β, IL-6, tumor necrosis factor (TNF) -α, matrix metalloproteinases (MMP) -1, MMP-3, and MMP-13. High-frequency near-infrared diode laser irradiation significantly reduced the IL-1β-induced expression of IL-1β, IL-6, TNF-α, MMP-1, and MMP-3. Similarly, high-frequency near-infrared diode laser irradiation decreased the IL-1β-induced increase in protein expression and secreted levels of MMP-1 and MMP-3. These results highlight the therapeutic potential of high-frequency near-infrared diode laser irradiation in OA.

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Section: Discussionmentioning

confidence: 90%

High-Frequency Near-Infrared Diode Laser Irradiation Attenuates IL-1β-Induced Expression of Inflammatory Cytokines and Matrix Metalloproteinases in Human Primary Chondrocytes

Sakata

Kunimatsu

Tsuka

et al. 2020

JCM

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“…ICA, the extract of Epimedium, is known to have anti-oxidative, anti-neuroinflammatory, and anti-apoptotic effects and considered to be effective for a range of disorders, such as neoplasm, Alzheimer's disease, cerebral ischemia, depression, diabetes, and Parkinson's disease (PD) [22][23][24][25]. For OA, ICA was identified as an anti-osteoporotic and anti-inflammatory compound through multi-target mechanisms, including the suppression of NF-κB signaling and inhibition of MMP1, MMP3, and MMP13 expression or OPG-RANKL-RANK system via MAPK pathways [13][14][15]. The present study demonstrated that ICA inhibited LPS-mediated chondrocytes injury and pyroptosis and alleviated rat osteoarthritis by inhibiting NLRP3 and caspase-1 signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Studies revealed that ICA prevented OA inflammation and chondrocytes apoptosis though activation of autophagy via inhibiting NF-κB signaling pathway [13]. Furthermore, ICA exerted a chondroprotective effect through the inhibition of MMP-1, MMP-3, and MMP-13 or the suppression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), and receptor activator of nuclear factor kappa-B (RANK) system via MAPK pathway in IL-1β-stimulated chondrosarcoma cells [14,15]. However, the molecular mechanisms of ICA alleviating OA and its relationship with NLRP3 inflammasome are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Icariin alleviates osteoarthritis by inhibiting NLRP3-mediated pyroptosis

Zu¹,

Mu²,

Li³

et al. 2019

J Orthop Surg Res

141

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Background Osteoarthritis (OA) is the common chronic degenerative joint bone disease that is mainly featured by joint stiffness and cartilage degradation. Icariin (ICA), an extract from Epimedium, has been preliminarily proven to show anti-osteoporotic and anti-inflammatory effects in OA. However, the underlying mechanisms of ICA on chondrocytes need to be elucidated. Methods LPS-treated chondrocytes and monosodium iodoacetate (MIA)-treated Wistar rats were used as models of OA in vitro and in vivo, respectively. LDH and MTT assays were performed to detect cytotoxicity and cell viability. The expression levels of NLRP3, IL-1β, IL-18, MMP-1, MMP-13, and collagen II were detected by qRT-PCR and Western blotting. The release levels of IL-1β and IL-18 were detected by ELISA assay. Caspase-1 activity was assessed by flow cytometry. Immunofluorescence and immunohistochemistry were used to examine the level of NLRP3 in chondrocytes and rat cartilage, respectively. The progression of OA was monitored with hematoxylin-eosin (H&E) staining and safranin O/fast green staining. Results ICA could suppress LPS-induced inflammation and reduction of collagen formation in chondrocytes. Furthermore, ICA could inhibit NLRP3 inflammasome-mediated caspase-1 signaling pathway to alleviate pyroptosis induced by LPS. Overexpression of NLRP3 reversed the above changes caused by ICA. It was further confirmed in the rat OA model that ICA alleviated OA by inhibiting NLRP3-mediated pyroptosis. Conclusion ICA inhibited OA via repressing NLRP3/caspase-1 signaling-mediated pyroptosis in models of OA in vitro and in vivo, suggesting that ICA might be a promising compound in the treatment of OA.

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“…Activation of the MAPK signaling pathway may lead to the secretion of several matrix-degrading proteinases, including the MMPs and the aggrecanases, leading to articular cartilage breakdown. IL-1β, the major proinflammatory cytokine involved the progression of OA, can easily activated the MAPK pathways ( 27 , 28 ). Thus, in our study, we investigated whether the anti-inflammatory effects of Kaempferol were through the attenuation of MAPK.…”

Section: Discussionmentioning

confidence: 99%

Kaempferol inhibits interleukin‑1β stimulated matrix metalloproteinases by suppressing the MAPK‑associated ERK and P38 signaling pathways

et al. 2018

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Osteoarthritis (OA) is a common degenerative joint disease in older adults. A number of previous studies have demonstrated that natural flavonoids can serve as promising therapeutic drugs for OA. Kaempferol, a phytochemical ingredient mainly present in various fruits, has exhibited its prominent anti-inflammatory and antioxidant effects in numerous diseases. However, whether Kaempferol ameliorates the deterioration of arthritis remains to be elucidated. The aim of the present study was to investigate the therapeutic role of Kaempferol on OA in rat chondrocytes. The results revealed that Kaempferol significantly inhibited the interleukin (IL)-1β-induced protein expression of inflammatory mediators such as inducible nitric oxide synthase and cyclo-oxygenase-2. In addition, the common matrix degrading enzymes [matrix metalloproteinase (MMP)-1, MMP-3, MMP-13 and a disintegrin and metalloproteinase with thrombospondin motif-5] induced by IL-1β were also suppressed by Kaempferol, and consequently abolished the degradation of collagen II. Furthermore, the anti-inflammatory effect of Kaempferol was mediated by the inhibition of the mitogen activated protein kinase-associated extracellular signal-regulated kinase and P38 signaling pathways. These results collectively indicated that Kaempferol can potentially prevent OA development and serve as a novel pharmacological target in the treatment of OA.

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Icariin inhibits MMP-1, MMP-3 and MMP-13 expression through MAPK pathways in IL-1β-stimulated SW1353 chondrosarcoma cells

Cited by 44 publications

References 22 publications

High-Frequency Near-Infrared Diode Laser Irradiation Attenuates IL-1β-Induced Expression of Inflammatory Cytokines and Matrix Metalloproteinases in Human Primary Chondrocytes

High-Frequency Near-Infrared Diode Laser Irradiation Attenuates IL-1β-Induced Expression of Inflammatory Cytokines and Matrix Metalloproteinases in Human Primary Chondrocytes

Icariin alleviates osteoarthritis by inhibiting NLRP3-mediated pyroptosis

Kaempferol inhibits interleukin‑1β stimulated matrix metalloproteinases by suppressing the MAPK‑associated ERK and P38 signaling pathways

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