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Research Article
Heidi Reesink
Cornell University
Corresponding Author
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Background
Lameness is a debilitating condition in equine athletes that leads to more performance limitation and loss of use than any other medical condition. There are a limited number of non-terminal experimental models that can be used to study early inflammatory and synovial fluid biophysical changes that occur in the equine joint. Here, we compare the well-established carpal IL-1β-induced synovitis model to a tarsal intra-articular lavage model, focusing on serial changes in synovial fluid inflammatory cytokines/chemokines and the synovial fluid lubricating molecules lubricin/proteoglycan 4 and hyaluronic acid. The objectives of this study were to evaluate clinical signs; synovial membrane and synovial fluid inflammation; and synovial fluid lubricants and biophysical properties in response to carpal IL-1β synovitis and tarsal intra-articular lavage.
Results
Hyaluronic acid (HA) concentrations, especially high molecular weight HA, and synovial fluid viscosity decreased after both synovitis and lavage interventions. Synovial fluid lubricin concentrations increased 17-20-fold for both synovitis and lavage models, with similar changes in both affected and contralateral joints, suggesting that repeated arthrocentesis alone resulted in elevated synovial fluid lubricin concentrations. Synovitis resulted in a more severe inflammatory response based on clinical signs (temperature, heart rate, respiratory rate, lameness and joint effusion) and clinicopathological and biochemical parameters (white blood cell count, total protein, prostaglandin E2, sulfated glycosaminoglycans, tumor necrosis factor-α and CC chemokine ligands − 2, -3, -5 and − 11) as compared to lavage.
Conclusions
Synovial fluid lubricin increased in response to IL-1β synovitis and joint lavage but also as a result of repeated arthrocentesis. Frequent repeated arthrocentesis is associated with inflammatory changes, including increased sulfated glycosaminoglycan concentrations and decreased hyaluronic acid concentrations. Synovitis results in more significant inflammatory changes than joint lavage. Our data suggests that synovial fluid lubricin, TNF-α, CCL2, CCL3, CCL5, CCL11 and sGAG may be useful biomarkers for synovitis and post-lavage joint inflammation. Caution should be exercised when performing repeated arthrocentesis clinically or in experimental studies due to the inflammatory response and loss of HA and synovial fluid viscosity.
Keywords
repeated arthrocentesis, lubricin, hyaluronic acid, chemokine, rheology, lubrication, osteoarthritis
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No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementalData1.pdf
Supplemental Data 1.pdf - Heart rate (HR), temperature (T), respiratory rate (RR), and joint circumference (JC) following IL-1β induced synovitis or intra-articular lavage. Graphs depicting changes in heart rate, temperature, respiratory rate and joint circumference following induction of synovitis and intra-articular lavage.
- SupplementalData2.pdf
Supplemental Data 2.pdf - Mean and standard error of the mean for the non-adjusted parameters measured in synovial fluid following synovitis induction and intra-articular lavage of the MCJ and TCJ. Data table of the means and standard error of the means for the unadjusted data described in the paper.
- SupplementalData3.pdf
Supplemental Data 3.pdf - Equine gene names, accession numbers, primer sequences and amplicon sizes for qRT-PCR Table of primers used for gene expression analysis used in this paper.
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CURRENT STATUS: Under Review
Version 1
Posted 19 Feb, 2021
No community comments so far
Editorial decision: Major revision
On 02 Mar, 2021
Reviews received
Received 22 Feb, 2021
Reviewers agreed
On 12 Feb, 2021
Reviewers invited
Invitations sent on 11 Feb, 2021
Editor assigned
On 11 Feb, 2021
Editor invited
On 11 Feb, 2021
Submission checks complete
On 11 Feb, 2021
First submitted
On 06 Feb, 2021
Metrics
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A new preprint design is coming!
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This preprint is under consideration at BMC Veterinary Research. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Heidi Reesink
Cornell University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 19 Feb, 2021
No community comments so far
Editorial decision: Major revision
On 02 Mar, 2021
Reviews received
Received 22 Feb, 2021
Reviewers agreed
On 12 Feb, 2021
Reviewers invited
Invitations sent on 11 Feb, 2021
Editor assigned
On 11 Feb, 2021
Editor invited
On 11 Feb, 2021
Submission checks complete
On 11 Feb, 2021
First submitted
On 06 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Lameness is a debilitating condition in equine athletes that leads to more performance limitation and loss of use than any other medical condition. There are a limited number of non-terminal experimental models that can be used to study early inflammatory and synovial fluid biophysical changes that occur in the equine joint. Here, we compare the well-established carpal IL-1β-induced synovitis model to a tarsal intra-articular lavage model, focusing on serial changes in synovial fluid inflammatory cytokines/chemokines and the synovial fluid lubricating molecules lubricin/proteoglycan 4 and hyaluronic acid. The objectives of this study were to evaluate clinical signs; synovial membrane and synovial fluid inflammation; and synovial fluid lubricants and biophysical properties in response to carpal IL-1β synovitis and tarsal intra-articular lavage.
Results
Hyaluronic acid (HA) concentrations, especially high molecular weight HA, and synovial fluid viscosity decreased after both synovitis and lavage interventions. Synovial fluid lubricin concentrations increased 17-20-fold for both synovitis and lavage models, with similar changes in both affected and contralateral joints, suggesting that repeated arthrocentesis alone resulted in elevated synovial fluid lubricin concentrations. Synovitis resulted in a more severe inflammatory response based on clinical signs (temperature, heart rate, respiratory rate, lameness and joint effusion) and clinicopathological and biochemical parameters (white blood cell count, total protein, prostaglandin E2, sulfated glycosaminoglycans, tumor necrosis factor-α and CC chemokine ligands − 2, -3, -5 and − 11) as compared to lavage.
Conclusions
Synovial fluid lubricin increased in response to IL-1β synovitis and joint lavage but also as a result of repeated arthrocentesis. Frequent repeated arthrocentesis is associated with inflammatory changes, including increased sulfated glycosaminoglycan concentrations and decreased hyaluronic acid concentrations. Synovitis results in more significant inflammatory changes than joint lavage. Our data suggests that synovial fluid lubricin, TNF-α, CCL2, CCL3, CCL5, CCL11 and sGAG may be useful biomarkers for synovitis and post-lavage joint inflammation. Caution should be exercised when performing repeated arthrocentesis clinically or in experimental studies due to the inflammatory response and loss of HA and synovial fluid viscosity.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementalData1.pdf
Supplemental Data 1.pdf - Heart rate (HR), temperature (T), respiratory rate (RR), and joint circumference (JC) following IL-1β induced synovitis or intra-articular lavage. Graphs depicting changes in heart rate, temperature, respiratory rate and joint circumference following induction of synovitis and intra-articular lavage.
- SupplementalData2.pdf
Supplemental Data 2.pdf - Mean and standard error of the mean for the non-adjusted parameters measured in synovial fluid following synovitis induction and intra-articular lavage of the MCJ and TCJ. Data table of the means and standard error of the means for the unadjusted data described in the paper.
- SupplementalData3.pdf
Supplemental Data 3.pdf - Equine gene names, accession numbers, primer sequences and amplicon sizes for qRT-PCR Table of primers used for gene expression analysis used in this paper.
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