scholarly journals Inhibitory Effects of IL-6-Mediated Matrix Metalloproteinase-3 and -13 by Achyranthes japonica Nakai Root in Osteoarthritis and Rheumatoid Arthritis Mice Models

2021 ◽  
Vol 14 (8) ◽  
pp. 776
Author(s):  
Xiangyu Zhao ◽  
Dahye Kim ◽  
Godagama Gamaarachchige Dinesh Suminda ◽  
Yunhui Min ◽  
Jiwon Yang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinase ◽  
Inflammatory Cytokine ◽  
Articular Chondrocytes ◽  
Primary Cultures ◽  
Plate Thickness ◽  
Inhibitory Effects ◽  
Matrix Metalloproteinase 3 ◽  
Arthritis Models ◽  
Achyranthes Japonica

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.

scholarly journals Clinical significance of serum matrix metalloproteinase-3 level in patients with rheumatoid arthritis

Ensho Saisei ◽  
2005 ◽  
Vol 25 (1) ◽  
pp. 60-64 ◽  
Author(s):  
Hayato Nagasawa ◽  
Hideto Kameda ◽  
Koichi Amano ◽  
Tsutomu Takeuchi
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinase ◽  
Clinical Significance ◽  
Matrix Metalloproteinase 3

scholarly journals Possible involvement of matrix metalloproteinase-3 in the pathogenesis of macroprolactinaemia in some patients with rheumatoid arthritis

2013 ◽  
Vol 169 (2) ◽  
pp. 203-209 ◽  
Author(s):  
Takashi Adachi ◽  
Naoki Hattori ◽  
Takashi Ishihara ◽  
Hirokazu Iida ◽  
Takanori Saito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinase ◽  
The Elderly ◽  
Elderly Subjects ◽  
Gel Chromatography ◽  
Post Translational Modifications ◽  
Matrix Metalloproteinase 3 ◽  
Control Subjects ◽  
Antibody Titres ◽  
And Gender

ObjectiveMacroprolactin primarily comprises a complex of prolactin (PRL) and IgG molecules, particularly anti-PRL autoantibodies. However, it is unknown why autoantibodies against PRL develop in certain subjects. This study aimed to elucidate post-translational modifications in the PRL molecule that may be involved in the pathogenesis of macroprolactinaemia.MethodsMacroprolactinaemia was screened with a polyethylene glycol method in 238 patients with rheumatoid arthritis (RA) and 302 control subjects and confirmed by gel chromatography. We examined the relationship between macroprolactinaemia and several RA-related laboratory tests including matrix metalloproteinase-3 (MMP-3) and anti-cyclic citrullinated peptide (CCP) antibody titres. The effect of MMP-3 on the PRL molecule was examined by western blotting.ResultsPatients with RA exhibited a significantly higher prevalence of macroprolactinaemia (15/238; 6.3%) than the young control subjects (5/219 subjects; 2.3%), but the prevalence was not different from that observed in the elderly control subjects (5/83 subjects; 6.0%). The prevalence of macroprolactinaemia in patients with elevated MMP-3 levels (9.68%) was significantly higher than that in those with normal MMP-3 levels (2.63%). Digestion of PRL with MMP-3 produced vasoinhibins with several molecular species. Serum total and free PRL levels in RA patients were higher than those in the age- and gender-matched control subjects. The levels of macroprolactin were not significantly correlated with those of RA-specific anti-CCP antibody.ConclusionsWe speculate that elevated MMP-3 levels may lead to the formation of new epitopes on the PRL molecule that might trigger an immune response to produce anti-PRL autoantibodies in some patients with RA. Such post-translational modifications may possibly contribute to the increased prevalence of macroprolactinaemia in elderly subjects.

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