Obesity Contribution in Synthesis and Degradation of Cartilage Marker Through Inflammation Pathway in Osteoarthritis Patient: Analysis of Adiponectin, Leptin, Ykl-40 and Cartilage Oligomeric Matrix Proteinase (Comp) Synovial Fluid

AbstractMicroRNAs (miRNAs) encapsulated within exosomes can serve as essential regulators of intercellular communication and represent promising biomarkers of several aging-associated disorders. However, the relationship between exosomal miRNAs and osteoarthritis (OA)-related chondrocytes and synovial fibroblasts (SFCs) remain to be clarified. Herein, we profiled synovial fluid-derived exosomal miRNAs and explored the effects of exosomal miRNAs derived from SFCs on chondrocyte inflammation, proliferation, and survival, and further assessed their impact on cartilage degeneration in a surgically-induced rat OA model. We identified 19 miRNAs within synovial fluid-derived exosomes that were differentially expressed when comparing OA and control patients. We then employed a microarray-based approach to confirm that exosomal miRNA-126-3p expression was significantly reduced in OA patient-derived synovial fluid exosomes. At a functional level, miRNA-126-3p mimic treatment was sufficient to promote rat chondrocyte migration and proliferation while also suppressing apoptosis and IL-1β, IL-6, and TNF-α expression. SFC-miRNA-126-3p-Exos were able to suppress apoptotic cell death and associated inflammation in chondrocytes. Our in vivo results revealed that rat SFC-derived exosomal miRNA-126-3p was sufficient to suppress the formation of osteophytes, prevent cartilage degeneration, and exert anti-apoptotic and anti-inflammatory effects on articular cartilage. Overall, our findings indicate that SFC exosome‐delivered miRNA-126-3p can constrain chondrocyte inflammation and cartilage degeneration. As such, SFC-miRNA-126-3p-Exos may be of therapeutic value for the treatment of patients suffering from OA.

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Corrigendum to “Novel synovial fluid recovery method allows for quantification of a marker of arthritis in mice” [Osteoarthritis and Cartilage 2008;16(12): 1532–1538

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2011.11.001 ◽

2012 ◽

Vol 20 (1) ◽

pp. 68

Author(s):

D.R. Seifer ◽

B.D. Furman ◽

F. Guilak ◽

S.A. Olson ◽

S.C. Brooks ◽

...

Keyword(s):

Synovial Fluid ◽

Recovery Method ◽

And Cartilage

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

The American Journal of Sports Medicine ◽

10.1177/0363546517749834 ◽

2018 ◽

Vol 46 (4) ◽

pp. 890-899 ◽

Cited By ~ 20

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.

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Herbal Composition LI73014F2 Alleviates Articular Cartilage Damage and Inflammatory Response in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Molecules ◽

10.3390/molecules25225467 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5467

Author(s):

Hae Lim Kim ◽

Hae Jin Lee ◽

Dong-Ryung Lee ◽

Bong-Keun Choi ◽

Seung Hwan Yang

Keyword(s):

Articular Cartilage ◽

Synovial Fluid ◽

Inflammatory Mediators ◽

Curcuma Longa ◽

Weight Bearing ◽

Cartilage Damage ◽

Terminalia Chebula ◽

Boswellia Serrata ◽

Monosodium Iodoacetate ◽

And Cartilage

The aim of this study was to determine the anti-osteoarthritic effects of LI73014F2, which consists of Terminalia chebula fruit, Curcuma longa rhizome, and Boswellia serrata gum resin in a 2:1:2 ratio, in the monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. LI73014F2 was orally administered once per day for three weeks. Weight-bearing distribution and arthritis index (AI) were measured once per week to confirm the OA symptoms. Synovial membrane, proteoglycan layer, and cartilage damage were investigated by histological examination, while synovial fluid interleukin-1β level was analyzed using a commercial kit. Levels of pro-inflammatory mediators/cytokines and matrix metalloproteinases (MMPs) in the cartilage tissues were investigated to confirm the anti-osteoarthritic effects of LI73014F2. LI73014F2 significantly inhibited the MIA-induced increase in OA symptoms, synovial fluid cytokine, cartilage damage, and expression levels of pro-inflammatory mediators/cytokines and MMPs in the articular cartilage. These results suggest that LI73014F2 exerts anti-osteoarthritic effects by regulating inflammatory cytokines and MMPs in MIA-induced OA rats.

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Synovial fluid levels of tumor necrosis factor α and oncostatin M correlate with levels of markers of the degradation of crosslinked collagen and cartilage aggrecan in rheumatoid arthritis but not in osteoarthritis

Arthritis & Rheumatism ◽

10.1002/1529-0131(200002)43:2<281::aid-anr7>3.0.co;2-7 ◽

2000 ◽

Vol 43 (2) ◽

pp. 281 ◽

Cited By ~ 72

Author(s):

Daniel-Henri Manicourt ◽

Pascal Poilvache ◽

Anne Van Egeren ◽

Jean-Pierre Devogelaer ◽

Mary-Ellen Lenz ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Synovial Fluid ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Oncostatin M ◽

Factor Α ◽

Fluid Levels ◽

Necrosis Factor ◽

And Cartilage

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Recombinant equine growth hormone administration: effects on synovial fluid biomarkers and cartilage metabolism in horses

Equine Veterinary Journal ◽

10.2746/042516403776148165 ◽

2010 ◽

Vol 35 (3) ◽

pp. 302-307 ◽

Cited By ~ 9

Author(s):

A. J. DART ◽

C. B. LITTLE ◽

C. E. HUGHES ◽

Q. CHU ◽

B. A. DOWLING ◽

...

Keyword(s):

Growth Hormone ◽

Synovial Fluid ◽

Growth Hormone Administration ◽

Cartilage Metabolism ◽

Hormone Administration ◽

And Cartilage

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Correlations between metabolites in the synovial fluid and serum: a mouse injury study

10.1101/2021.08.30.458234 ◽

2021 ◽

Author(s):

Cameron W Wallace ◽

Brady D Hislop ◽

Alyssa K Hahn ◽

Ayten Ebru Erdogan ◽

Priyanka P Brahmachary ◽

...

Keyword(s):

Amino Acid ◽

Synovial Fluid ◽

Acid Synthesis ◽

Post Injury ◽

Amino Acid Synthesis ◽

Joint Injury ◽

Serum Metabolites ◽

Time Points ◽

Insight Into ◽

Synthesis And Degradation

Osteoarthritis, the most common degenerative joint disease, occurs more frequently in joints that have sustained injury. Currently, osteoarthritis is diagnosed with imaging that finds radiographic changes after the disease has already progressed to multiple tissues. The primary objective of this study was to compare potential metabolomic biomarkers of joint injury between the synovial fluid and serum in a mouse model of post-traumatic osteoarthritis. The secondary objective was to gain insight into the pathophysiology of osteoarthritis by examining metabolomic profiles after joint injury. 12-week-old adult female C57BL/6 mice (n=12) were randomly assigned to control, day 1 post injury, or day 8 post injury groups. Randomly selected stifle (i.e., knee) joints were placed into a non-invasive injury apparatus and subjected to a single dynamic axial compression causing anterior translation of the tibia relative to the femur to tear the anterior cruciate ligament. At days 1 and 8 post injury, serum was extracted then mice were immediately euthanized prior to synovial fluid collection. Metabolites were extracted and analyzed by liquid chromatography coupled to mass spectrometry. We detected ~2500 metabolites across serum and synovial fluid. Of these metabolites 179 were positively correlated and 51 were negatively correlated between synovial fluid and serum, indicating potential for the development of metabolomic biomarkers. Synovial fluid appeared to capture differences in metabolomic profiles between injured mice at both day 1 and 8 after injury whereas serum did not. However, synovial fluid and serum were distinct at both days 1 and 8 after injury. In the synovial fluid, pathways of interest across different time points mapped to amino acid synthesis and degradation, bupropion degradation, and the tRNA charging pathway. In the serum, notable pathways across time points were amino acid synthesis and degradation, the phospholipase pathway, and nicotine degradation. These results provide a rich picture of the injury response at early time points following traumatic joint injury. Furthermore, the correlations between synovial fluid and serum metabolites suggest that there is potential to gain insight into intra-articular pathophysiology through analysis of serum metabolites.

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