scholarly journals 5-Aza-2′-deoxycytidine and interleukin-1 cooperate to regulate matrix metalloproteinase-3 gene expression

2011 ◽  
Vol 129 (9) ◽  
pp. 2083-2092 ◽  
Author(s):  
Julie Couillard ◽  
Pierre-Olivier Estève ◽  
Sriharsa Pradhan ◽  
Yves St-Pierre
2002 ◽  
Vol 46 (11) ◽  
pp. 3034-3040 ◽  
Author(s):  
Anthony N. Corps ◽  
Rebecca L. Harrall ◽  
Valerie A. Curry ◽  
Steven A. Fenwick ◽  
Brian L. Hazleman ◽  
...  

2011 ◽  
Vol 39 (11) ◽  
pp. 2362-2370 ◽  
Author(s):  
Gerben M. van Buul ◽  
Wendy L.M. Koevoet ◽  
Nicole Kops ◽  
P. Koen Bos ◽  
Jan A.N. Verhaar ◽  
...  

Background: Platelet-rich plasma (PRP) has recently been postulated as a treatment for osteoarthritis (OA). Although anabolic effects of PRP on chondrocytes are well documented, no reports are known addressing effects on cartilage degeneration. Since OA is characterized by a catabolic and inflammatory joint environment, the authors investigated whether PRP was able to counteract the effects of such an environment on human osteoarthritic chondrocytes. Hypothesis: Platelet-rich plasma inhibits inflammatory effects of interleukin-1 (IL-1) beta on human osteoarthritic chondrocytes. Study Design: Controlled laboratory study. Methods: Human osteoarthritic chondrocytes were cultured in the presence of IL-1 beta to mimic an osteoarthritic environment. Medium was supplemented with 0%, 1%, or 10% PRP releasate (PRPr, the active releasate of PRP). After 48 hours, gene expression of collagen type II alpha 1 (COL2A1), aggrecan (ACAN), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, ADAMTS5, matrix metalloproteinase (MMP)13, and prostaglandin-endoperoxide synthase (PTGS)2 was analyzed. Additionally, glycosaminoglycan (GAG) content, nitric oxide (NO) production, and nuclear factor kappa B (NFκB) activation were studied. Results: Platelet-rich plasma releasate diminished IL-1 beta–induced inhibition of COL2A1 and ACAN gene expression. The PRPr also reduced IL-1 beta–induced increase of ADAMTS4 and PTGS2 gene expression. ADAMTS5 gene expression and GAG content were not influenced by IL-1 beta or additional PRPr. Matrix metalloproteinase 13 gene expression and NO production were upregulated by IL-1 beta but not affected by added PRPr. Finally, PRPr reduced IL-1 beta–induced NFκB activation to control levels containing no IL-1 beta. Conclusion: Platelet-rich plasma releasate diminished multiple inflammatory IL-1 beta–mediated effects on human osteoarthritic chondrocytes, including inhibition of NFκB activation. Clinical Relevance: Platelet-rich plasma releasate counteracts effects of an inflammatory environment on genes regulating matrix degradation and formation in human chondrocytes. Platelet-rich plasma releasate decreases NFκB activation, a major pathway involved in the pathogenesis of OA. These results encourage further study of PRP as a treatment for OA.


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252163
Author(s):  
Chun-Hao Chang ◽  
Yun-Li Lin ◽  
Yeu-Sheng Tyan ◽  
Yun-Hsuan Chiu ◽  
Ya-Han Liang ◽  
...  

Human umbilical cord Wharton’s jelly derived mesenchymal stem cells (hUCMSCs), a source of cell therapy, have received a great deal of attention due to their homing or migrating ability in response to signals emanating from damaged sites. It has been found that IL-1β possesses the ability to induce the expression of matrix metalloproteinase-3 (MMP-3) in bone marrow MSCs. MMP-3 is involved in cell migration in various types of cells, including glioblastoma, vascular smooth muscle, and adult neural progenitor cells. In this study, we proposed that IL-1β influences hUCMSCs migration involving MMP-3. The expression level of MMP-3 in IL-1β-induced hUCMSCs was verified using cDNA microarray analysis, quantitative real-time PCR, ELISA and Western blot. Wound-healing and trans-well assay were used to investigate the cell migration and invasion ability of IL-1β-treated hUCMSCs. In addition, we pre-treated hUCMSCs with interleukin-1 receptor antagonist, MMP-3 inhibitors (ALX-260-165, UK 356618), or transfected with MMP-3 siRNA to confirm the role of MMP3 in IL-1β-induced cell migration. Our results showed that IL-1β induced MMP-3 expression is related to the migration of hUCMSCs. Moreover, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126, p38 inhibitor SB205380, JNK inhibitor SP600125 and Akt inhibitor GSK 690693 decreased IL-1β-induced MMP-3 mRNA and protein expression. The migration and invasion ability analyses showed that these inhibitors attenuated the IL-1β-induced migration and invasion ability of hUCMSCs. In conclusion, we have found that IL-1β induces the expression of MMP-3 through ERK1/2, JNK, p38 MAPK and Akt signaling pathways to enhance the migration of hUCMSCs. These results provide further understanding of the mechanisms in IL-1β-induced hUCMSCs migration to injury sites.


2007 ◽  
Vol 27 (11) ◽  
pp. 1049-1055 ◽  
Author(s):  
Deh-Ming Chang ◽  
Shao-Hsiang Liu ◽  
Herng-Sheng Lee ◽  
Jenn-Hung Lai ◽  
Chen-Hung Chen

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