Synovial Fluid Biomarkers in Knee Osteoarthritis: A Systematic Review and Quantitative Evaluation Using BIPEDs Criteria

Boffa, Angelo; Merli, Giulia; Andriolo, Luca; Lattermann, Christian; Salzmann, Gian M.; Filardo, Giuseppe

doi:10.1177/1947603520942941

Cited by 52 publications

(44 citation statements)

References 176 publications

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“…24 Notably, while recent meta-analyses demonstrated that elevated MMP-3 is a consistent diagnostic marker for osteoarthritis, these have cast doubt on whether MMP-3 levels alone reliably correlate with osteoarthritis severity. 7 Subsequently, some studies report the ratio of MMP-3 to TIMP-1 expression to evaluate changes in metalloproteinase-mediated cartilage damage. 11,33,51 Our analysis demonstrated a significant increase in the MMP-3 to TIMP-1 ratio during the acute postinjury period.…”

Section: Discussionmentioning

confidence: 99%

Changes in the Synovial Fluid Cytokine Profile of the Knee Between an Acute Anterior Cruciate Ligament Injury and Surgical Reconstruction

et al. 2022

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Background: Changes in the intra-articular inflammatory state during the immediate period after an acute anterior cruciate ligament (ACL) rupture are not well defined. Purpose: To evaluate changes in the concentration of select proinflammatory and anti-inflammatory synovial fluid cytokines during the interval between an ACL injury and surgical reconstruction. Study Design: Descriptive laboratory study. Methods: In patients with an acute ACL injury, a synovial fluid sample was obtained from the injured knee during the initial office visit within 2 weeks of the inciting traumatic event. An additional synovial fluid sample was collected at the time of ACL reconstruction just before the surgical incision. Synovial fluid samples from both the acute injury and the surgery time points were processed with a protease inhibitor, and the concentrations of 10 cytokines of interest were measured using a multiplex magnetic bead immunoassay. The primary outcome was the change in cytokine concentrations between time points. Results: A total of 20 patients with a mean age of 30.2 ± 8.3 years were included. The acute injury synovial fluid samples were collected at 6.6 ± 3.8 days after the injury. The surgical synovial fluid samples were collected at 31.6 ± 15.6 days after the acute injury samples. Based on a series of linear mixed-effects models to control for the effect of concomitant meniscal injuries and by-patient variability, there was a statistically significant increase in the concentrations of RANTES and bFGF and a statistically significant decrease in the concentrations of IL-6, MCP-1, MIP-1β, TIMP-1, IL-1Ra, and VEGF between time points. Conclusion: This study demonstrates the ongoing alterations in the intra-articular microenvironment during the initial inflammatory response in the acute postinjury period. We identified 6 synovial fluid cytokines that significantly decreased and 2 that significantly increased between the first clinical presentation shortly after the injury and the time of surgery 1 month later. Clinical Relevance: This study describes the molecular profile of the inflammatory changes between the time of an acute ACL injury and the time of surgical reconstruction 1 month later. A greater understanding of the acute inflammatory response within the knee may be helpful in identifying the optimal timing for a surgical intervention that balances the risk of chondral damage with the likelihood of successful, well-healed reconstruction.

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Section: Discussionmentioning

confidence: 99%

Changes in the Synovial Fluid Cytokine Profile of the Knee Between an Acute Anterior Cruciate Ligament Injury and Surgical Reconstruction

et al. 2022

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“…Our results showed that tissue viability could be maintained during the culture period. Cartilage of these explants presented a similar inflammatory response like in human OA joints with respect to findings of histology, gene expression, and analysis of supernatant conditioned medium (Martel-Pelletier et al, 2016;Robinson et al, 2016;Boffa et al, 2020).…”

Section: Discussionmentioning

confidence: 62%

Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants

Zhang

Zhu

et al. 2021

Front. Bioeng. Biotechnol.

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Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Although various animal models exist, the translation of the outcome into clinics remains difficult due to species differences. In this study, an ex vivo inflammatory OA model was induced using different concentrations of interleukin one beta (IL-1β) and tumor necrosis factor α (TNF-α) on explants from the human femoral head. In the inflammatory OA groups, the gene expression levels of cartilage catabolism (matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3)), and inflammation (interleukin 6 (IL-6), interleukin 8 (IL-8)) markers were significantly upregulated, while the anabolic genes (collagen 2 (COL2), aggrecan (ACAN), and proteoglycan 4 (PRG4)) were downregulated compared to the control group. The release of cytokines (IL-6, IL-8) and nitric oxide (NO) in the conditioned medium was also upregulated in inflammatory OA groups. The Safranin O/Fast Green staining showed loss of proteoglycan in the superficial zone cartilage after cytokine treatment. The results indicated that an ex vivo inflammation and degeneration model was successfully established using osteochondral explants from the human femoral head. This model can be used to elucidate the in-depth mechanism of inflammatory OA and to screen new drugs for OA treatment.

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“…In 6 of the 7 studies, there was a significantly positive correlation between osteoarthritis severity and VEGF. 91 …”

Section: Vascular Epithelial Growth Factor (Vegf)mentioning

confidence: 99%

Cross-Communication Between Knee Osteoarthritis and Fibrosis: Molecular Pathways and Key Molecules

Bolia¹,

Mertz²,

Faye³

et al. 2022

OAJSM

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Knee fibrosis is characterized by the presence of excessive connective tissue due to dysregulated fibroblast activation following local or systemic tissue damage. Knee fibrosis constitutes a major clinical problem in orthopaedics due to the severe limitation in the knee range of motion that leads to compromised function and patient disability. Knee osteoarthritis is an extremely common orthopedic condition that is associated with patient disability and major costs to the health-care systems worldwide. Although knee fibrosis and osteoarthritis (OA) have traditionally been perceived as two separate pathologic entities, recent research has shown common ground between the pathophysiologic processes that lead to the development of these two conditions. The purpose of this review was to identify the pathophysiologic pathways as well as key molecules that are implicated in the development of both knee OA and knee fibrosis in order to understand the relationship between the two diagnoses and potentially identify novel therapeutic targets.

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Synovial Fluid Biomarkers in Knee Osteoarthritis: A Systematic Review and Quantitative Evaluation Using BIPEDs Criteria

Cited by 52 publications

References 176 publications

Changes in the Synovial Fluid Cytokine Profile of the Knee Between an Acute Anterior Cruciate Ligament Injury and Surgical Reconstruction

Changes in the Synovial Fluid Cytokine Profile of the Knee Between an Acute Anterior Cruciate Ligament Injury and Surgical Reconstruction

Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants

Cross-Communication Between Knee Osteoarthritis and Fibrosis: Molecular Pathways and Key Molecules

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