scholarly journals The impact of anterior cruciate ligament injury on lubricin metabolism and the effect of inhibiting tumor necrosis factor α on chondroprotection in an animal model

2009 ◽  
Vol 60 (10) ◽  
pp. 2997-3006 ◽  
Author(s):  
K. A. Elsaid ◽  
J. T. Machan ◽  
K. Waller ◽  
B. C. Fleming ◽  
G. D. Jay
Keyword(s):  
Animal Model ◽  
Anterior Cruciate Ligament ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Cruciate Ligament ◽  
Ligament Injury ◽  
Anterior Cruciate ◽  
Factor Α ◽  
The Impact ◽  
Necrosis Factor

scholarly journals Synovial Fluid Profile at the Time of Anterior Cruciate Ligament Reconstruction and Its Association With Cartilage Matrix Composition 3 Years After Surgery

2018 ◽  
Vol 46 (4) ◽  
pp. 890-899 ◽  
Author(s):  
Keiko Amano ◽  
Janet L. Huebner ◽  
Thomas V. Stabler ◽  
Matthew Tanaka ◽  
Charles E. McCulloch ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Synovial Fluid ◽  
Ligament Reconstruction ◽  
Cruciate Ligament ◽  
Matrix Composition ◽  
Sulfated Glycosaminoglycan ◽  
Anterior Cruciate ◽  
Factor Α ◽  
Necrosis Factor ◽  
And Cartilage

Background: Anterior cruciate ligament tears can lead to posttraumatic osteoarthritis. In addition to biomechanical factors, changes in biochemical profiles within the knee joint after injury and anterior cruciate ligament reconstruction (ACLR) may play a role in accelerating joint degeneration. Hypothesis/Purpose: It was hypothesized that cartilage matrix composition after ACLR is associated with the degree of inflammatory response after initial injury. This study evaluated the association between the inflammatory response after injury—as indicated by cytokine, metalloproteinase, and cartilage degradation marker concentrations in synovial fluid—and articular cartilage degeneration, measured by T1ρ and T2 quantitative magnetic resonance imaging up to 3 years after ACLR. Study Design: Cohort study; Level of evidence, 2. Methods: Twenty-six subjects from a longitudinal cohort study who underwent ACLR at a mean 8.5 weeks after injury (range, 4-19 weeks) had synovial fluid aspirated at the time of surgery. Immunoassays quantified biomarkers in synovial fluid. T1ρ and T2 values of articular cartilage were calculated with magnetic resonance scans acquired prior to surgery and at 6 months and 1, 2, and 3 years after surgery. Pearson correlation coefficients were calculated among the various biomarkers. K-means clustering was used to group subjects with similar biomarker profiles. Generalized estimating equations were used to find the overall differences in T1ρ and T2 values throughout these first 3 years after surgery between the clusters while controlling for other factors. Results: Significant and strong correlations were observed between several cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α) and 2 matrix metalloproteinases (MMP-1 and MMP-3) ( P < .05). Moderate correlations were found among combinations of C-terminal crosslinked telopeptide type II collagen, N-terminal telopeptide, cartilage oligomeric matrix protein, and sulfated glycosaminoglycan ( P < .05). Two clusters were generated, 1 of which was characterized by lower concentrations of cytokines (IL-6, IL-8, IL-10, tumor necrosis factor α) and MMP-1 and MMP-3 and higher sulfated glycosaminoglycan. This cluster was associated with significantly higher T1ρ and T2 values in the medial tibial and patellar cartilage over the first 3 years after ACLR. Conclusion: At the time of ACLR surgery, profiles of synovial fluid inflammatory cytokines, degradative enzymes, and cartilage breakdown products show promise as predictors of abnormal cartilage tissue integrity (increased T1ρ and T2 values) throughout the first 3 years after surgery. Clinical Relevance: The results suggest an intricate relationship between inflammation and cartilage turnover, which can in turn be influenced by timing after injury and patient factors.

scholarly journals Expression of LOXs and MMP-1, 2, 3 by ACL Fibroblasts and Synoviocytes Impact of Coculture and TNF-α

2018 ◽  
Vol 32 (04) ◽  
pp. 352-360 ◽  
Author(s):  
Chunli Wang ◽  
Qingjia Chi ◽  
Chunming Xu ◽  
Kang Xu ◽  
Yanjun Zhang ◽  
...  
Keyword(s):  
Cruciate Ligament ◽  
Cartilage Degradation ◽  
Ligament Injury ◽  
Tnf Α ◽  
Gene And Protein Expression ◽  
Polymerase Chain ◽  
Anterior Cruciate ◽  
Factor Α ◽  
First Time ◽  
Necrosis Factor

AbstractThis study aims to confirm the effects of synoviocytes (SCs) on regulating lysyl oxidases (LOXs) and matrix metalloproteinase (MMP)-1, 2, 3 in the normal and injured anterior cruciate ligament (ACL) fibroblasts response to tumor necrosis factor-α(TNF-α). The gene and protein expression levels of LOXs and MMP-1, 2, 3 in SCs cocultured ACL fibroblasts (ACLfs) induced by TNF-α and mechanical injury were analyzed by real-time polymerase chain reaction (PCR) and western bolting; the MMP-2 activity were analyzed by zymography. The results exhibited that TNF-α alone slightly downregulated the expressions of LOXs and upregulated the expression of MMP-1, 2, 3 in both normal and injured ACL fibroblasts. The decrease of LOXs and increase of MMP-1, 2, 3 in ACLfs response to TNF-α were further promoted by coculture. Taken together, these results show for the first time that the crosstalk between ACLfs and SCs could modulate the LOXs and MMP-1, 2, 3 synthesis in ACLfs in the presence of TNF-α. Accumulation of MMPs in the isolated fluid-containing space not only disrupts the balance of ACL healing, but also increases cartilage degradation and accelerates osteoarthritis (OA) in injured joint. Based on this mechanism, targeting inhibition of MMPs could provide a promising therapeutic strategy for acute ligament injury.

Accelerated Atherosclerosis in Rheumatoid Arthritis: Mechanisms and Treatment

2019 ◽  
Vol 25 (9) ◽  
pp. 969-986 ◽  
Author(s):  
Allison B. Reiss ◽  
Andrew Silverman ◽  
Muhammed Khalfan ◽  
Nicholas A. Vernice ◽  
Lora J. Kasselman ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Cyclooxygenase Inhibitors ◽  
Disease Modifying ◽  
Factor Α ◽  
The Impact ◽  
Necrosis Factor

Background:Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disorder that increases the risk of developing cardiovascular disease. There is accumulating evidence that the RA disease state accelerates the formation of atherosclerotic plaques. Treatments for RA improve joint symptomatology and may reduce inflammation, but consideration of their effects on the cardiovascular system is generally low priority.Objective:Since cardiovascular disease is the leading cause of mortality in RA patients, the impact of RA therapies on atherosclerosis is an area in need of attention and the focus of this review.Results:The drugs used to treat RA may be analgesics, conventional disease-modifying anti-rheumatic drugs, and/or biologics, including antibodies against the cytokine tumor necrosis factor-α. Pain relievers such as nonselective non-steroidal anti-inflammatory drugs and cyclooxygenase inhibitors may adversely affect lipid metabolism and cyclooxygenase inhibitors have been associated with increased adverse cardiovascular events, such as myocardial infarction and stroke. Methotrexate, the anchor disease-modifying anti-rheumatic drug in RA treatment has multiple atheroprotective advantages and is often combined with other therapies. Biologic inhibitors of tumor necrosis factor-α may be beneficial in preventing cardiovascular disease because tumor necrosis factor-α promotes the initiation and progression of atherosclerosis. However, some studies show a worsening of the lipid profile in RA with blockade of this cytokine, leading to higher total cholesterol and triglycerides.Conclusion:Greater understanding of the pharmacologic activity of RA treatments on the atherosclerotic process may lead to improved care, addressing both damages to the joints and heart.

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