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Paper 33: Serum and Urine Biomarkers for Treatment Monitoring after Meniscal Allograft Transplantation in a Preclinical Canine Model
OBJECTIVES: To analyze serum and urine biomarker concentrations for their capabilities in delineating differences in assessments of pain and functional outcomes after meniscus allograft transplantation (MAT) in a preclinical canine model. The study was designed to test the hypothesis that serum and...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339880/ http://dx.doi.org/10.1177/2325967121S00597 |
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author | Stoker, Aaron Leary, Emily Bozynski, Chantelle Stannard, James Cook, James Ewing, Michael |
author_facet | Stoker, Aaron Leary, Emily Bozynski, Chantelle Stannard, James Cook, James Ewing, Michael |
author_sort | Stoker, Aaron |
collection | PubMed |
description | OBJECTIVES: To analyze serum and urine biomarker concentrations for their capabilities in delineating differences in assessments of pain and functional outcomes after meniscus allograft transplantation (MAT) in a preclinical canine model. The study was designed to test the hypothesis that serum and urine biomarkers could be used for prognostic (1- and 3-month post-surgical time points) and diagnostic (6-month time point) assessments, based on strong associations with clinically relevant pain and function outcomes after MAT. METHODS: Twelve adult, purpose-bred research hounds were included and underwent medial meniscal release (MR) to induce medial compartment gonarthrosis. Three months following MR, medial MAT was performed using: fresh-frozen meniscus (n=4), fresh meniscus (n=4), or fresh menisco-tibial OCA (n=4). Serum and urine from all dogs were collected preoperatively and at 1, 3, and 6 months following MAT. Validated outcome measures for pain, function, effusion, knee range of motion, and gait kinetics were collected at these same timepoints. To develop a prognostic panel of biomarkers, biomarker data from the 1-month and 3-month post-MAT surgery timepoints were used to model 6-month outcomes. A diagnostic panel of biomarkers was developed using biomarker data from the 6-month post-MAT surgery to model 6-month outcomes. RESULTS: Across prognostic biomarker panels, serum biomarkers were mainly represented. A panel including serum IL-6, IL-8, IL-10, and IL-18 had strong model fit for prognostication of the gait kinetics outcome, operated limb %Total Pressure Index (%TPI) (R(2)=.45). Whereas, a biomarker panel including serum CTX-II and OPG had strong model fit for prognostication of the primary pain-related outcome, VAS pain (R(2)=.52). Across diagnostic biomarker panels, a panel including serum MMP-1 and MMP-3 and urine PINP and TIMP-1 had strong model fit as diagnostic biomarkers for %TPI (R(2)=.86). Whereas, a panel including urine CTX-I, CTX-II, IL-8, MMP-2, and TIMP-1 had strong model fit as diagnostic biomarkers for VAS pain (R(2)=.44). CONCLUSIONS: Biomarker panels of selected serum and/or urine proteins highly correlate with clinically-relevant metrics for pain and function outcomes in a preclinical model of meniscus allograft transplantation. |
format | Online Article Text |
id | pubmed-9339880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-93398802022-08-02 Paper 33: Serum and Urine Biomarkers for Treatment Monitoring after Meniscal Allograft Transplantation in a Preclinical Canine Model Stoker, Aaron Leary, Emily Bozynski, Chantelle Stannard, James Cook, James Ewing, Michael Orthop J Sports Med Article OBJECTIVES: To analyze serum and urine biomarker concentrations for their capabilities in delineating differences in assessments of pain and functional outcomes after meniscus allograft transplantation (MAT) in a preclinical canine model. The study was designed to test the hypothesis that serum and urine biomarkers could be used for prognostic (1- and 3-month post-surgical time points) and diagnostic (6-month time point) assessments, based on strong associations with clinically relevant pain and function outcomes after MAT. METHODS: Twelve adult, purpose-bred research hounds were included and underwent medial meniscal release (MR) to induce medial compartment gonarthrosis. Three months following MR, medial MAT was performed using: fresh-frozen meniscus (n=4), fresh meniscus (n=4), or fresh menisco-tibial OCA (n=4). Serum and urine from all dogs were collected preoperatively and at 1, 3, and 6 months following MAT. Validated outcome measures for pain, function, effusion, knee range of motion, and gait kinetics were collected at these same timepoints. To develop a prognostic panel of biomarkers, biomarker data from the 1-month and 3-month post-MAT surgery timepoints were used to model 6-month outcomes. A diagnostic panel of biomarkers was developed using biomarker data from the 6-month post-MAT surgery to model 6-month outcomes. RESULTS: Across prognostic biomarker panels, serum biomarkers were mainly represented. A panel including serum IL-6, IL-8, IL-10, and IL-18 had strong model fit for prognostication of the gait kinetics outcome, operated limb %Total Pressure Index (%TPI) (R(2)=.45). Whereas, a biomarker panel including serum CTX-II and OPG had strong model fit for prognostication of the primary pain-related outcome, VAS pain (R(2)=.52). Across diagnostic biomarker panels, a panel including serum MMP-1 and MMP-3 and urine PINP and TIMP-1 had strong model fit as diagnostic biomarkers for %TPI (R(2)=.86). Whereas, a panel including urine CTX-I, CTX-II, IL-8, MMP-2, and TIMP-1 had strong model fit as diagnostic biomarkers for VAS pain (R(2)=.44). CONCLUSIONS: Biomarker panels of selected serum and/or urine proteins highly correlate with clinically-relevant metrics for pain and function outcomes in a preclinical model of meniscus allograft transplantation. SAGE Publications 2022-07-28 /pmc/articles/PMC9339880/ http://dx.doi.org/10.1177/2325967121S00597 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc-nd/4.0/This open-access article is published and distributed under the Creative Commons Attribution - NonCommercial - No Derivatives License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits the noncommercial use, distribution, and reproduction of the article in any medium, provided the original author and source are credited. You may not alter, transform, or build upon this article without the permission of the Author(s). For article reuse guidelines, please visit SAGE’s website at http://www.sagepub.com/journals-permissions. |
spellingShingle | Article Stoker, Aaron Leary, Emily Bozynski, Chantelle Stannard, James Cook, James Ewing, Michael Paper 33: Serum and Urine Biomarkers for Treatment Monitoring after Meniscal Allograft Transplantation in a Preclinical Canine Model |
title | Paper 33: Serum and Urine Biomarkers for Treatment Monitoring after Meniscal Allograft Transplantation in a Preclinical Canine Model |
title_full | Paper 33: Serum and Urine Biomarkers for Treatment Monitoring after Meniscal Allograft Transplantation in a Preclinical Canine Model |
title_fullStr | Paper 33: Serum and Urine Biomarkers for Treatment Monitoring after Meniscal Allograft Transplantation in a Preclinical Canine Model |
title_full_unstemmed | Paper 33: Serum and Urine Biomarkers for Treatment Monitoring after Meniscal Allograft Transplantation in a Preclinical Canine Model |
title_short | Paper 33: Serum and Urine Biomarkers for Treatment Monitoring after Meniscal Allograft Transplantation in a Preclinical Canine Model |
title_sort | paper 33: serum and urine biomarkers for treatment monitoring after meniscal allograft transplantation in a preclinical canine model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339880/ http://dx.doi.org/10.1177/2325967121S00597 |
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