Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation

Inflammation ◽  
1994 ◽  
Vol 18 (6) ◽  
pp. 613-623 ◽  
Author(s):  
Masao Shingu ◽  
Tetsurou Isayama ◽  
Chie Yasutake ◽  
Takashi Naono ◽  
Masashi Nobunaga ◽  
...  
Keyword(s):  
Oxygen Radicals ◽  
Cartilage Matrix ◽  
Matrix Degradation

Oxygen radicals mediate IL-1-dependent cartilage matrix degradation through autocrine mechanisms

1990 ◽  
Vol 9 ◽  
pp. 147
Author(s):  
Masao Shingu ◽  
Masashi Nobunaga ◽  
Satoshi Shiokawa ◽  
Masahiro Yamamoto
Keyword(s):  
Oxygen Radicals ◽  
Cartilage Matrix ◽  
Matrix Degradation

THE ROLE OF IL-4 AND IL-6 IN IL-1-DEPENDENT CARTILAGE MATRIX DEGRADATION

Rheumatology ◽  
1995 ◽  
Vol 34 (2) ◽  
pp. 101-106 ◽  
Author(s):  
M. SHINGU ◽  
S. MIYAUCHI ◽  
Y. NAGAI ◽  
C. YASUTAKE ◽  
K. HORIE
Keyword(s):  
Cartilage Matrix ◽  
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-211-5p contributes to chondrocyte differentiation by suppressing Fibulin-4 expression to play a role in osteoarthritis

2019 ◽  
Vol 166 (6) ◽  
pp. 495-502 ◽  
Author(s):  
Hao Liu ◽  
Jun Luo
Keyword(s):  
Inflammatory Cytokines ◽  
Rat Model ◽  
Cartilage Matrix ◽  
Chondrocyte Differentiation ◽  
Matrix Degradation ◽  
Downstream Target ◽  
Promising Target ◽  
Human Disorders ◽  
Pro Inflammatory Cytokines

Abstract MicroRNAs (miRNAs) serve as key regulators in human disorders. Previous research reported that miR-211-5p is down-regulated in osteoarthritis (OA) and that Fibulin-4 inhibits chondrocyte differentiation. However, the role of miR-211-5p in the development of OA has not been clarified, and its downstream target has not been studied. This study aimed to explore the effect of miR-211-5p on chondrocyte differentiation and its influence on OA pathogenesis, as well as the interaction between miR-211-5p and Fibulin-4. In this study, we found that miR-211-5p is significantly down-regulated in articular cartilage tissues in an OA rat model, whereas it is clearly up-regulated during chondrocyte differentiation of ATDC5 cells. Silencing miR-211-5p in ATDC5 cells had an adverse effect on chondrocyte differentiation. Fibulin-4 was identified as a target of miR-211-5p, and miR-211-5p participated in chondrocyte differentiation by negatively regulating Fibulin-4 expression. In the OA rat model, miR-211-5p overexpression facilitated chondrocyte differentiation, along with the reduced pro-inflammatory cytokines level and the level of proteinases responsible for cartilage matrix degradation. In summary, miR-211-5p promotes chondrocyte differentiation by negatively regulating Fibulin-4 expression, and represses the expression of pro-inflammatory cytokines and proteinases responsible for cartilage matrix degradation in OA. miR-211-5p may serve as a promising target for OA treatment.

scholarly journals EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 388
Author(s):  
Brice Chanez ◽  
Kevin Ostacolo ◽  
Ali Badache ◽  
Sylvie Thuault
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Focal Adhesions ◽  
Matrix Degradation ◽  
Cancer Cell Invasion ◽  
Wild Type ◽  
Spatial Regulation ◽  
Invadopodia Formation

Regulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential for cancer cell invasion and metastasis, the leading cause of death in breast cancer. We, therefore, investigated the role of the End Binding protein, EB1, a major hub of the +TIP network, in invadopodia functions. EB1 silencing increased matrix degradation by breast cancer cells. This was recapitulated by depletion of two additional +TIPs and EB1 partners, APC and ACF7, but not by the knockdown of other +TIPs, such as CLASP1/2 or CLIP170. The knockdown of Focal Adhesion Kinase (FAK) was previously proposed to similarly promote invadopodia formation as a consequence of a switch of the Src kinase from focal adhesions to invadopodia. Interestingly, EB1-, APC-, or ACF7-depleted cells had decreased expression/activation of FAK. Remarkably, overexpression of wild type FAK, but not of FAK mutated to prevent Src recruitment, prevented the increased degradative activity induced by EB1 depletion. Overall, we propose that EB1 restricts invadopodia formation through the control of FAK and, consequently, the spatial regulation of Src activity.

scholarly journals Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor

2021 ◽  
Vol 13 (1) ◽  
pp. 17-29
Author(s):  
Emann M Rabie ◽  
Sherry X Zhang ◽  
Andreas P Kourouklis ◽  
A Nihan Kilinc ◽  
Allison K Simi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Type I ◽  
Matrix Degradation ◽  
Human Breast ◽  
Rate Of Invasion

Abstract Metastasis, the leading cause of mortality in cancer patients, depends upon the ability of cancer cells to invade into the extracellular matrix that surrounds the primary tumor and to escape into the vasculature. To investigate the features of the microenvironment that regulate invasion and escape, we generated solid microtumors of MDA-MB-231 human breast carcinoma cells within gels of type I collagen. The microtumors were formed at defined distances adjacent to an empty cavity, which served as an artificial vessel into which the constituent tumor cells could escape. To define the relative contributions of matrix degradation and cell proliferation on invasion and escape, we used pharmacological approaches to block the activity of matrix metalloproteinases (MMPs) or to arrest the cell cycle. We found that blocking MMP activity prevents both invasion and escape of the breast cancer cells. Surprisingly, blocking proliferation increases the rate of invasion but has no effect on that of escape. We found that arresting the cell cycle increases the expression of MMPs, consistent with the increased rate of invasion. To gain additional insight into the role of cell proliferation in the invasion process, we generated microtumors from cells that express the fluorescent ubiquitination-based cell cycle indicator. We found that the cells that initiate invasions are preferentially quiescent, whereas cell proliferation is associated with the extension of invasions. These data suggest that matrix degradation and cell proliferation are coupled during the invasion and escape of human breast cancer cells and highlight the critical role of matrix proteolysis in governing tumor phenotype.

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 Levels of Circulating TIMP-2 and MMP2-TIMP2 Complex Are Decreased in Squamous Cervical Carcinoma

2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
Talvensaari-Mattila Anne ◽  
Turpeenniemi-Hujanen Taina
Keyword(s):  
Cervical Carcinoma ◽  
Matrix Metalloproteinase 2 ◽  
Healthy Controls ◽  
Matrix Degradation ◽  
Serum Samples ◽  
Study Population ◽  
The Mean ◽  
Natural Tissue ◽  
Squamous Cervical Carcinoma

Background. The role of matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) in matrix degradation and metastasis has been described in various tumors. Their action is inhibited by their natural tissue inhibitor molecules TIMP-1 and -2.Methods. The study population consisted of 12 squamous cervical carcinoma patients and 27 healthy volunteer control patients. MMP-9, MMP-2-TIMP-2 complex, TIMP-1, and TIMP-2 were analyzed from serum samples using enzyme-linked immunoassay (ELISA).Results. The mean levels of serum TIMP-2 and of MMP-2-TIMP-2 complex were higher in healthy controls compared to patients with a malignant tumor. Serum TIMP-2 values decreased significantly from healthy controls (median 323 g/l, range 305–342 g/l) to malignant (median 136 g/l, range 120–151 g/l) squamous cervical carcinoma patients . Also, serum proMMP2-TIMP2 complex values decreased from control patients to squamous cervical carcinoma patients .Conclusion. This paper shows that the levels of circulating TIMP-2 and that of MMP-2-TIMP-2 complex are lower in squamous cervical carcinoma patients than in healthy women.

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