Inhibitory effects of melittin on the production of lipopolysaccharide-induced matrix metalloproteinase 3 in human osteoarthritic chondrocytes

Toxicon ◽  
2007 ◽  
Vol 49 (6) ◽  
pp. 881-885 ◽  
Author(s):  
Seong-Su Nah ◽  
Eunyoung Ha ◽  
Hye-Jung Lee ◽  
Joo-Ho Chung
2021 ◽  
Vol 14 (8) ◽  
pp. 776
Author(s):  
Xiangyu Zhao ◽  
Dahye Kim ◽  
Godagama Gamaarachchige Dinesh Suminda ◽  
Yunhui Min ◽  
Jiwon Yang ◽  
...  

Achyranthes japonica Nakai root (AJNR) is used to treat osteoarthritis (OA) and rheumatoid arthritis (RA) owing to its anti-inflammatory and antioxidant effects. This study investigated the inhibitory effects of AJNR on arthritis. AJNR was extracted using supercritical carbon dioxide (CO2), and its main compounds, pimaric and kaurenoic acid, were identified. ANJR’s inhibitory effects against arthritis were evaluated using primary cultures of articular chondrocytes and two in vivo arthritis models: destabilization of the medial meniscus (DMM) as an OA model, and collagenase-induced arthritis (CIA) as an RA model. AJNR did not affect pro-inflammatory cytokine (IL-1β, TNF-α, IL-6)-mediated cytotoxicity, but attenuated pro-inflammatory cytokine-mediated increases in catabolic factors, and recovered pro-inflammatory cytokine-mediated decreases in related anabolic factors related to in vitro. The effect of AJNR is particularly specific to IL-6-mediated catabolic or anabolic alteration. In a DMM model, AJNR decreased cartilage erosion, subchondral plate thickness, osteophyte size, and osteophyte maturity. In a CIA model, AJNR effectively inhibited cartilage degeneration and synovium inflammation in either the ankle or knee and reduced pannus formation in both the knee and ankle. Immunohistochemistry analysis revealed that AJNR mainly acted via the inhibitory effects of IL-6-mediated matrix metalloproteinase-3 and -13 in both arthritis models. Therefore, AJNR is a potential therapeutic agent for relieving arthritis symptoms.


2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 432.1-432
Author(s):  
K. Ikuta ◽  
Y. Waguri-Nagaya ◽  
N. Tatematsu ◽  
Y. Kawaguchi ◽  
T. Terazawa ◽  
...  

2008 ◽  
Vol 28 (7) ◽  
pp. 2391-2413 ◽  
Author(s):  
Takanori Eguchi ◽  
Satoshi Kubota ◽  
Kazumi Kawata ◽  
Yoshiki Mukudai ◽  
Junji Uehara ◽  
...  

ABSTRACT Matrix metalloproteinase 3 (MMP3) is well known as a secretory endopeptidase that degrades extracellular matrices. Recent reports indicated the presence of MMPs in the nucleus (A. J. Kwon et al., FASEB J. 18:690-692, 2004); however, its function has not been well investigated. Here, we report a novel function of human nuclear MMP3 as a trans regulator of connective tissue growth factor (CCN2/CTGF). Initially, we cloned MMP3 cDNA as a DNA-binding factor for the CCN2/CTGF gene. An interaction between MMP3 and transcription enhancer dominant in chondrocytes (TRENDIC) in the CCN2/CTGF promoter was confirmed by a gel shift assay and chromatin immunoprecipitation. The CCN2/CTGF promoter was activated by overexpressed MMP3, whereas a TRENDIC mutant promoter lost the response. Also, the knocking down of MMP3 suppressed CCN2/CTGF expression. By cytochemical and histochemical analyses, MMP3 was detected in the nuclei of chondrocytic cells in culture and also in the nuclei of normal and osteoarthritic chondrocytes in vivo. The nuclear translocation of externally added recombinant MMP3 and six putative nuclear localization signals in MMP3 also were shown. Furthermore, we determined that heterochromatin protein gamma coordinately regulates CCN2/CTGF by interacting with MMP3. The involvement of this novel role of MMP3 in the development, tissue remodeling, and pathology of arthritic diseases through CCN2/CTGF regulation thus is suggested.


PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e83563 ◽  
Author(s):  
Taiki Hiyama ◽  
Nobuaki Ozeki ◽  
Makio Mogi ◽  
Hideyuki Yamaguchi ◽  
Rie Kawai ◽  
...  

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