META060 inhibits osteoclastogenesis and matrix metalloproteinases in vitro and reduces bone and cartilage degradation in a mouse model of rheumatoid arthritis

2010 ◽  
Vol 62 (6) ◽  
pp. 1683-1692 ◽  
Author(s):  
Veera Reddy Konda ◽  
Anuradha Desai ◽  
Gary Darland ◽  
Jeffrey S. Bland ◽  
Matthew L. Tripp
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinases ◽  
Mouse Model ◽  
Cartilage Degradation ◽  
And Cartilage

scholarly journals Exosome-transported circRNA_0001236 enhances chondrogenesis and suppress cartilage degradation via the miR-3677-3p/Sox9 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guping Mao ◽  
Yiyang Xu ◽  
Dianbo Long ◽  
Hong Sun ◽  
Hongyi Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mouse Model ◽  
Chondrogenic Differentiation ◽  
Cartilage Degradation ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Luciferase Reporter ◽  
Gene And Protein Expression

Abstract Objectives Aberrations in exosomal circular RNA (circRNA) expression have been identified in various human diseases. In this study, we investigated whether exosomal circRNAs could act as competing endogenous RNAs (ceRNAs) to regulate the pathological process of osteoarthritis (OA). This study aimed to elucidate the specific MSC-derived exosomal circRNAs responsible for MSC-mediated chondrogenic differentiation using human bone marrow-derived MSCs (hMSCs) and a destabilization of the medial meniscus (DMM) mouse model of OA. Methods Exosomal circRNA deep sequencing was performed to evaluate the expression of circRNAs in human bone marrow-derived MSCs (hMSCs) induced to undergo chondrogenesis from day 0 to day 21. The regulatory and functional roles of exosomal circRNA_0001236 were examined on day 21 after inducing chondrogenesis in hMSCs and were validated in vitro and in vivo. The downstream target of circRNA_0001236 was also explored in vitro and in vivo using bioinformatics analyses. A luciferase reporter assay was used to evaluate the interaction between circRNA_0001236 and miR-3677-3p as well as the target gene sex-determining region Y-box 9 (Sox9). The function and mechanism of exosomal circRNA_0001236 in OA were explored in the DMM mouse model. Results Upregulation of exosomal circRNA_0001236 enhanced the expression of Col2a1 and Sox9 but inhibited that of MMP13 in hMSCs induced to undergo chondrogenesis. Moreover, circRNA_0001236 acted as an miR-3677-3p sponge and functioned in human chondrocytes via targeting miR-3677-3p and Sox9. Intra-articular injection of exosomal circRNA_0001236 attenuated OA in the DMM mouse model. Conclusions Our results reveal an important role for a novel exosomal circRNA_0001236 in chondrogenic differentiation. Overexpression of exosomal circRNA_0001236 promoted cartilage-specific gene and protein expression through the miR-3677-3p/Sox9 axis. Thus, circRNA_0001236-overexpressing exosomes may alleviate cartilage degradation, suppressing OA progression and enhancing cartilage repair. Our findings provide a potentially effective therapeutic strategy for treating OA.

In Vitro Sensitivity of the Three Mammalian Collagenases to Tetracycline Inhibition: Relationship to Bone and Cartilage Degradation

Bone ◽  
1998 ◽  
Vol 22 (1) ◽  
pp. 33-38 ◽  
Author(s):  
R.A Greenwald ◽  
L.M Golub ◽  
N.S Ramamurthy ◽  
M Chowdhury ◽  
S.A Moak ◽  
...  
Keyword(s):  
Cartilage Degradation ◽  
In Vitro Sensitivity ◽  
And Cartilage

scholarly journals Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures

2006 ◽  
Vol 54 (10) ◽  
pp. 3152-3162 ◽  
Author(s):  
Ursula Fearon ◽  
Ronan Mullan ◽  
Trevor Markham ◽  
Mary Connolly ◽  
Shane Sullivan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Cartilage Degradation ◽  
Rheumatoid Arthritis Synovial Tissue ◽  
Oncostatin M ◽  
Human Cartilage ◽  
And Cartilage

58 The plaminogen activation system in bone and cartilage degradation in vitro and in vivo

1997 ◽  
Vol 11 ◽  
pp. 17
Author(s):  
Jan Verheijen ◽  
Karel Ronday ◽  
Jeroen de Roos ◽  
Ferry Breedveld ◽  
Johan te Koppele ◽  
...  
Keyword(s):  
Cartilage Degradation ◽  
Activation System ◽  
And Cartilage

scholarly journals Loss of the WNT9a ligand aggravates the rheumatoid arthritis-like symptoms in hTNF transgenic mice

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Stefan Teufel ◽  
Petra Köckemann ◽  
Christine Fabritius ◽  
Lena I. Wolff ◽  
Jessica Bertrand ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Soft Tissue ◽  
Mouse Model ◽  
Wnt Signaling ◽  
Joint Destruction ◽  
Wnt Signaling Pathway ◽  
Synovial Fibroblasts ◽  
Canonical Wnt

AbstractAgonists and antagonists of the canonical Wnt signaling pathway are modulators of pathological aspects of rheumatoid arthritis (RA). Their activity is primarily modifying bone loss and bone formation, as shown in animal models of RA. More recently, modulation of Wnt signaling by the antagonist Sclerostin has also been shown to influence soft-tissue-associated inflammatory aspects of the disease pointing towards a role of Wnt signaling in soft-tissue inflammation as well. Yet, nothing is known experimentally about the role of Wnt ligands in RA. Here we provide evidence that altering Wnt signaling at the level of a ligand affects all aspects of the rheumatoid arthritic disease. WNT9a levels are increased in the pannus tissue of RA patients, and stimulation of synovial fibroblasts (SFB) with tumor necrosis factor (TNF) leads to increased transcription of Wnt9a. Loss of Wnt9a in a chronic TNF-dependent RA mouse model results in an aggravation of disease progression with enhanced pannus formation and joint destruction. Yet, loss of its activity in the acute K/BxN serum-transfer induced arthritis (STIA) mouse model, which is independent of TNF signaling, has no effect on disease severity or progression. Thus, suggesting a specific role for WNT9a in TNF-triggered RA. In synovial fibroblasts, WNT9a can activate the canonical Wnt/β-catenin pathway, but it can also activate P38- and downregulate NFκB signaling. Based on in vitro data, we propose that loss of Wnt9a creates a slight proinflammatory and procatabolic environment that boosts the TNF-mediated inflammatory response.

scholarly journals The Novel Synthetic Peptide AESIS-1 Exerts a Preventive Effect on Collagen-Induced Arthritis Mouse Model via STAT3 Suppression

2020 ◽  
Vol 21 (2) ◽  
pp. 378
Author(s):  
Kyung Eun Kim ◽  
Suwon Jeon ◽  
Jisun Song ◽  
Tae Sung Kim ◽  
Min Kyung Jung ◽  
...  
Keyword(s):  
Mouse Model ◽  
Synthetic Peptide ◽  
Specific Inhibitor ◽  
Cytokine Signaling ◽  
The Novel ◽  
Collagen Induced Arthritis ◽  
Stat3 Phosphorylation ◽  
And Cartilage

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is associated with systemic inflammation and results in the destruction of joints and cartilage. The pathogenesis of RA involves a complex inflammatory process resulting from the action of various proinflammatory cytokines and, therefore, many novel therapeutic agents to block cytokines or cytokine-mediated signaling have been developed. Here, we tested the preventive effects of a small peptide, AESIS-1, in a mouse model of collagen-induced arthritis (CIA) with the aim of identifying a novel safe and effective biological for treating RA. This novel peptide significantly suppressed the induction and development of CIA, resulting in the suppression of synovial inflammation and cartilage degradation in vivo. Moreover, AESIS-1 regulated JAK/STAT3-mediated gene expression in vitro. In particular, the gene with the most significant change in expression was suppressor of cytokine signaling 3 (Socs3), which was enhanced 8-fold. Expression of the STAT3-specific inhibitor, Socs3, was obviously enhanced dose-dependently by AESIS-1 at both the mRNA and protein levels, resulting in a significant reduction of STAT3 phosphorylation in splenocytes from severe CIA mice. This indicated that AESIS-1 regulated STAT3 activity by upregulation of SOCS3 expression. Furthermore, IL-17 expression and the frequency of Th17 cells were considerably decreased by AESIS-1 in vivo and in vitro. Collectively, our data suggest that the novel synthetic peptide AESIS-1 could be an effective therapeutic for treating RA via the downregulation of STAT3 signaling.

ILThe Infl uence of Resveratrol on the Synovial Expression of Matrix Metalloproteinases and Receptor Activator of NF-κB Ligand in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

2013 ◽  
Vol 68 (7-8) ◽  
pp. 336-342
Author(s):  
Mathias Glehr ◽  
Margherita Breisach ◽  
Sonja Walzer ◽  
Birgit Lohberger ◽  
Florentine Fürst ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinases ◽  
Nuclear Factor Κb ◽  
Qrt Pcr ◽  
Pharmacological Studies ◽  
Receptor Activator ◽  
Polymerase Chain ◽  
Fibroblast Like Synoviocytes

Medication of rheumatoid arthritis (RA) remains challenging and often controversial concerning side effects or long-term complications. We investigated the effect of resveratrol, a phytoalexin discussed for its chondro-protective and anti-inflammatory qualities, on the synovial expression of matrix-degrading enzymes like matrix metalloproteinases (MMPs) and bone-remodelling proteins in RA fibroblast-like synoviocytes (FLS). Interleukin-1β- stimulated RA-FLS were treated with 100 μM resveratrol for 24 h. To evaluate the effect of resveratrol on the amount of bound/combined MMPs, a Luminex® xMAP multiplexing technology was used. The alteration in expression of receptor activator of nuclear factor- κB ligand (RANKL) and osteoprotegrin (OPG) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Resveratrol reduced the expression of MMP-1 (p = 0.022), MMP-3 (p = 0.021), and MMP-9 (p = 0.047). qRT-PCR showed a significant reduction in the relative abundance of the transcripts of OPG (p = 0.012) and RANKL (p = 0.018). Our in vitro findings indicate that resveratrol could be a new target for further pharmacological studies in the field of RA. In the future it could play a role as a possible substitute or supplement to currently used drugs against RA to prevent cartilage matrix degradation and pathological bone resorption due to inhibition of MMPs and RANKL

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