Paeonol Ameliorates Inflammation and Cartilage of Chondrocytes in Osteoarthritis by Upregulating SIRT1

2020 ◽  
Author(s):  
Peng Shang ◽  
Ying Liu ◽  
Junqing Jia
Keyword(s):  
Extracellular Matrix ◽  
Caspase 3 ◽  
Type Ii Collagen ◽  
Blue Staining ◽  
Chondrocyte Apoptosis ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation ◽  
Tnf Α ◽  
And Cartilage

Abstract Objective: To explore the possible role of paeonol on chondrocyte inflammation and cartilage protection in osteoarthritis (OA).Methods: Primary chondrocytes were isolated from rat stifle joints, and were identified through toluidine blue staining and immunofluorescence staining of type II collagen. The chondrocytes were transfected with sh-SIRT1 or/and paeonol (0, 20, 50, 100, 200, 1000 mg/L) before OA modeling induced by IL-1β. ELISA determined the expressions of TNF-α, IL-17 and IL-6, and apoptotic rate was examined by flow cytometry. qRT-PCR and Western blot quantified the expressions of MMP-1, MMP-3, MMP-13, TIMP-1, cleaved-caspase-3, Bax, Bcl-2, and the proteins related to NF-κB pathway.Results: Increases in TNF-α, IL-17, IL-6, MMP-1, MMP-3 and MMP-13 and decrease in TIMP-1 were found in IL-1β stimulated chondrocytes. The apoptotic rate as well as the expressions of cleaved-caspase-3 and Bax was up-regulated, and Bcl-2 expression was suppressed in response to IL-1β treatment. NF-κB pathway was activated in IL-1β-stimulated chondrocytes. Paeonol enhanced SIRT1 expression to inactivate NF-κB pathway, thus ameliorating the secretion of inflammatory cytokines, extracellular matrix degradation and chondrocyte apoptosis.Conclusion: Paeonol inhibits IL-1β induced inflammation and extracellular matrix degradation in chondrocytes through up-regulating SIRT1 and suppressing NF-κB pathway.

scholarly journals A740003 Can Reverse Chondrocyte Apoptosis and Prevent Extracellular Matrix Degradation by NF-KB Pathway in Facet Joint Osteoarthritis

2021 ◽  
Author(s):  
pengfei xue ◽  
Guanyin Wu ◽  
huricha jin ◽  
jiawei jiang ◽  
Mo zhang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Facet Joint ◽  
Chondrocyte Apoptosis ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation ◽  
Facet Joint Osteoarthritis ◽  
Common Causes ◽  
Oa Chondrocytes ◽  
Apoptotic Effects

Abstract Facet joint osteoarthritis (FJOA) is one of the common causes of low back pain, but the molecular mechanism is still unclear. Previous studies have found that P2X7 receptor has been proved to play an important role in skeletal and joint diseases. The purpose of this study was to explore the role of A740003, selective P2X7R antagonist, in the development of FJOA. Our study found that A740003 can inhibit the expression of P2X7R in OA chondrocytes. It can lead to anti-inflammatory and anti-apoptotic effects in primary chondrocytes by IL-1β/BzATP. Our results imply that decreased P2X7R can reverse chondrocyte apoptosis and prevent extracellular matrix degradation by NF-KB pathway. Moreover, in our present work, we found that A740003 inhibit the abrrently activation of NF-KB pathway by preventing the activated P65 translocation to nucleus. Our results indicate that P2X7R is a therapeutic target for the treatment of FJOA, and that A740003 could be a therapeutic candidate for this clinical application.

scholarly journals The phosphatase Shp1 interacts with and dephosphorylates cortactin to inhibit invadopodia function

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Alessia Varone ◽  
Chiara Amoruso ◽  
Marcello Monti ◽  
Manpreet Patheja ◽  
Adelaide Greco ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tyrosine Phosphatase ◽  
Melanoma Cells ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation ◽  
Invadopodia Formation ◽  
Interference Rna

Abstract Background Invadopodia are actin-based cell-membrane protrusions associated with the extracellular matrix degradation accompanying cancer invasion. The elucidation of the molecular mechanisms leading to invadopodia formation and activity is central for the prevention of tumor spreading and growth. Protein tyrosine kinases such as Src are known to regulate invadopodia assembly, little is however known on the role of protein tyrosine phosphatases in this process. Among these enzymes, we have selected the tyrosine phosphatase Shp1 to investigate its potential role in invadopodia assembly, due to its involvement in cancer development. Methods Co-immunoprecipitation and immunofluorescence studies were employed to identify novel substrate/s of Shp1AQ controlling invadopodia activity. The phosphorylation level of cortactin, the Shp1 substrate identified in this study, was assessed by immunoprecipitation, in vitro phosphatase and western blot assays. Short interference RNA and a catalytically-dead mutant of Shp1 expressed in A375MM melanoma cells were used to evaluate the role of the specific Shp1-mediated dephosphorylation of cortactin. The anti-invasive proprieties of glycerophosphoinositol, that directly binds and regulates Shp1, were investigated by extracellular matrix degradation assays and in vivo mouse model of metastasis. Results The data show that Shp1 was recruited to invadopodia and promoted the dephosphorylation of cortactin at tyrosine 421, leading to an attenuated capacity of melanoma cancer cells to degrade the extracellular matrix. Controls included the use of short interference RNA and catalytically-dead mutant that prevented the dephosphorylation of cortactin and hence the decrease the extracellular matrix degradation by melanoma cells. In addition, the phosphoinositide metabolite glycerophosphoinositol facilitated the localization of Shp1 at invadopodia hence promoting cortactin dephosphorylation. This impaired invadopodia function and tumor dissemination both in vitro and in an in vivo model of melanomas. Conclusion The main finding here reported is that cortactin is a specific substrate of the tyrosine phosphatase Shp1 and that its phosphorylation/dephosphorylation affects invadopodia formation and, as a consequence, the ability of melanoma cells to invade the extracellular matrix. Shp1 can thus be considered as a regulator of melanoma cell invasiveness and a potential target for antimetastatic drugs.

scholarly journals Role of aminopeptidase N (CD13) in tumor-cell invasion and extracellular matrix degradation

1993 ◽  
Vol 54 (1) ◽  
pp. 137-143 ◽  
Author(s):  
Ikuo Saiki ◽  
Junya Yoneda ◽  
Ichiro Azuma ◽  
Hideji Fujii ◽  
Fuminori Abe ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Aminopeptidase N ◽  
Tumor Cell Invasion ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation

Erythropoietin protects post-ischemic hearts by preventing extracellular matrix degradation: Role of Jak2-ERK pathway

Life Sciences ◽  
2007 ◽  
Vol 81 (9) ◽  
pp. 717-723 ◽  
Author(s):  
Chih-Yang Chan ◽  
Yih-Sharng Chen ◽  
Hsang-Hsing Lee ◽  
Ho-Shiang Huang ◽  
Yih-Loong Lai ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Erk Pathway ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation

scholarly journals Acupuncture Delays Cartilage Degeneration through Upregulating SIRT1 Expression in Rats with Osteoarthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Hui Liu ◽  
Tingting Zhang ◽  
Min Liu ◽  
Chunhong Wang ◽  
Jinfeng Yan
Keyword(s):  
Cartilage Degeneration ◽  
Cartilage Matrix ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matrix Degradation ◽  
Matrix Synthesis ◽  
Sirt1 Expression ◽  
Tnf Α ◽  
Related Proteins ◽  
And Cartilage

Silent mating type information regulation 2 homolog 1 (SIRT1) has been reported to inhibit osteoarthritic gene expression in chondrocytes. Here, efforts in this study were made to unveil the specific role of SIRT1 in the therapy of acupuncture on cartilage degeneration in osteoarthritis (OA). Specifically, OA was established by the anterior cruciate ligament transection method in the right knee joint of rats, subsequent to which acupuncture was performed on two acupoints. Injection with shSIRT1 sequence–inserted lentiviruses was conducted to investigate the role of SIRT1 in acupuncture-mediated OA. Morphological changes and cell apoptosis in rat OA cartilages were examined by safranin-O staining and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay, respectively. The serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-2 in OA rats were assessed by enzyme-linked immunosorbent assay (ELISA). The expressions of SIRT1, cartilage matrix degradation-related proteins (matrix metalloproteinase (MMP)-9 and ADAMTS5), NF-κB signaling-related markers (p-p65/p65 and p-IκBα/IκBα), and cartilage matrix synthesis-related proteins (collagen II and aggrecan) in the OA cartilage were analyzed by western blot. As a result, acupuncture counteracted OA-associated upregulation of TNF-α, IL-2, cartilage matrix degradation-related proteins, and NF-κB signaling-related markers, morphological damage, apoptosis, SIRT1 downregulation, and loss of cartilage matrix synthesis-related proteins in rat articular cartilages. SIRT1 silencing reversed acupuncture-induced counteractive effects on the aforementioned OA-associated phenomena (except apoptosis, the experiment regarding which under SIRT1 silencing was not performed). Collectively, acupuncture inhibited chondrocyte apoptosis, inflammation, NF-κB signaling activation, and cartilage matrix degradation by upregulating SIRT1 expression to delay OA-associated cartilage degeneration.

MiR-30b-5p Influences Chronic Exercise Arthritic Injury by Targeting Hoxa1

2021 ◽  
Author(s):  
Maoxun Li ◽  
Fei Gai ◽  
Hongyu Chen
Keyword(s):  
Caspase 3 ◽  
Cartilage Lesion ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Chondrocyte Apoptosis ◽  
Chronic Exercise ◽  
Tnf Α ◽  
And Migration ◽  
Induced Apoptosis ◽  
Safranin O

AbstractWe identified the role of miR-30b-5p in chronic exercise arthritic injury. Rats with chronic exercise arthritic injury received treatment with miR-30b-5p antagomiR. H&E and Safranin O-fast green staining were performed. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected. The binding relationship between homeobox A1 (Hoxa1) and miR-30b-5p was revealed. After manipulating the expressions of miR-30b-5p and/or Hoxa1 in chondrocytes, the viability, apoptosis and migration of chondrocytes were assessed. The levels of molecules were determined by qRT-PCR or Western blot. MiR-30b-5p antagomiR ameliorated articular cartilage lesion and destruction, reduced Mankin’s score and the levels of TNF-α, IL-1β, miR-30b-5p, matrix metallopeptidase 13 (MMP-13), and cleaved caspase-3, and increased relative thickness and the levels of Hoxa1, Aggrecan and type II collagen (COLII) in model rats. MiR-30b-5p up-regulation decreased Hoxa1 level, viability, migration and induced apoptosis, whereas miR-30b-5p down-regulation produced the opposite effects. MiR-30b-5p up-regulation increased the levels of MMP-13 and cleaved caspase-3, but decreased those of Aggrecan and COLII in chondrocytes. However, the action of miR-30b-5p up-regulation on chondrocytes was reversed by Hoxa1 overexpression. In conclusion, miR-30b-5p is involved in cartilage degradation in rats with chronic exercise arthritic injury and regulates chondrocyte apoptosis and migration by targeting Hoxa1.

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