Proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co-morbid conditions

IntroductionDegenerative joint disease (DJD) occurs very commonly in cats and can be associated with pain. Almost 70% of cats with DJD-associated pain suffer the co-morbidity of chronic kidney disease (CKD). There are currently very limited treatment or management options. A greater understanding of...

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Main Authors: B. Duncan X. Lascelles, Rakesh Ponnala, Steven G. Kamerling, Tracey Williams
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Pain Research
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Online Access:https://www.frontiersin.org/articles/10.3389/fpain.2025.1501932/full
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author B. Duncan X. Lascelles
B. Duncan X. Lascelles
B. Duncan X. Lascelles
B. Duncan X. Lascelles
Rakesh Ponnala
Steven G. Kamerling
Tracey Williams
author_facet B. Duncan X. Lascelles
B. Duncan X. Lascelles
B. Duncan X. Lascelles
B. Duncan X. Lascelles
Rakesh Ponnala
Steven G. Kamerling
Tracey Williams
author_sort B. Duncan X. Lascelles
collection DOAJ
description IntroductionDegenerative joint disease (DJD) occurs very commonly in cats and can be associated with pain. Almost 70% of cats with DJD-associated pain suffer the co-morbidity of chronic kidney disease (CKD). There are currently very limited treatment or management options. A greater understanding of the systems biology of DJD, DJD-associated pain, and CKD may contribute to identifying disease specific biomarkers and relevant targets for the development of therapeutics for the control of these conditions in cats, and help inform human pain therapeutic development.MethodsUsing mass spectrometry-based proteomic profiling of the serum of 200 highly phenotyped cats with varying burdens of DJD, pain, and CKD, we identified significant individual proteins and pathways.ResultsFunctional pathway analysis, based on differentially abundant proteins across individual disease states (DJD, pain, CKD), identified pathways playing a role in DJD and DJD-associated pain including acute phase response signaling, LXR/RXR and FXR/RXR activation and the complement system. With the added co-morbidity of CKD, similar pathways were identified, with the addition of IL-12 signaling and production in macrophages.DiscussionWe identified differentially abundant proteins associated with DJD, pain and CKD and future work should evaluate these proteins as potential biomarkers of disease (individually or as clusters). Further, these data could be leveraged to identify novel therapeutic targets to address the gap in our ability to manage DJD, pain, and CKD in cats. Given that our work was in cats with naturally occurring DJD, these results may have translational applicability to human health.
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spelling doaj-art-0b2bc4c0a3ea405e898950d10b22e9512025-02-04T06:31:44ZengFrontiers Media S.A.Frontiers in Pain Research2673-561X2025-02-01610.3389/fpain.2025.15019321501932Proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co-morbid conditionsB. Duncan X. Lascelles0B. Duncan X. Lascelles1B. Duncan X. Lascelles2B. Duncan X. Lascelles3Rakesh Ponnala4Steven G. Kamerling5Tracey Williams6Translational Research in Pain, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesComparative Pain Research and Education Center, North Carolina State University, Raleigh, NC, United StatesThurston Arthritis Center, UNC School of Medicine, Chapel Hill, NC, United StatesCenter for Translational Pain Research, Department of Anesthesiology, Duke University, Durham, NC, United StatesVeterinary Medicine Research & Development, Zoetis, Kalamazoo, MI, United StatesVeterinary Pharmacology Consultant, Veterinary Medicine Research & Development, Zoetis, Kalamazoo, MI, United StatesVeterinary Medicine Research & Development, Zoetis, Kalamazoo, MI, United StatesIntroductionDegenerative joint disease (DJD) occurs very commonly in cats and can be associated with pain. Almost 70% of cats with DJD-associated pain suffer the co-morbidity of chronic kidney disease (CKD). There are currently very limited treatment or management options. A greater understanding of the systems biology of DJD, DJD-associated pain, and CKD may contribute to identifying disease specific biomarkers and relevant targets for the development of therapeutics for the control of these conditions in cats, and help inform human pain therapeutic development.MethodsUsing mass spectrometry-based proteomic profiling of the serum of 200 highly phenotyped cats with varying burdens of DJD, pain, and CKD, we identified significant individual proteins and pathways.ResultsFunctional pathway analysis, based on differentially abundant proteins across individual disease states (DJD, pain, CKD), identified pathways playing a role in DJD and DJD-associated pain including acute phase response signaling, LXR/RXR and FXR/RXR activation and the complement system. With the added co-morbidity of CKD, similar pathways were identified, with the addition of IL-12 signaling and production in macrophages.DiscussionWe identified differentially abundant proteins associated with DJD, pain and CKD and future work should evaluate these proteins as potential biomarkers of disease (individually or as clusters). Further, these data could be leveraged to identify novel therapeutic targets to address the gap in our ability to manage DJD, pain, and CKD in cats. Given that our work was in cats with naturally occurring DJD, these results may have translational applicability to human health.https://www.frontiersin.org/articles/10.3389/fpain.2025.1501932/fullfelinedegenerative joint disease (DJD)osteoarthritis (OA)chronic kidney disease (CKD)pain
spellingShingle B. Duncan X. Lascelles
B. Duncan X. Lascelles
B. Duncan X. Lascelles
B. Duncan X. Lascelles
Rakesh Ponnala
Steven G. Kamerling
Tracey Williams
Proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co-morbid conditions
Frontiers in Pain Research
feline
degenerative joint disease (DJD)
osteoarthritis (OA)
chronic kidney disease (CKD)
pain
title Proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co-morbid conditions
title_full Proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co-morbid conditions
title_fullStr Proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co-morbid conditions
title_full_unstemmed Proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co-morbid conditions
title_short Proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co-morbid conditions
title_sort proteomic profiling of serum in cats with naturally occurring degenerative joint disease and co morbid conditions
topic feline
degenerative joint disease (DJD)
osteoarthritis (OA)
chronic kidney disease (CKD)
pain
url https://www.frontiersin.org/articles/10.3389/fpain.2025.1501932/full
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