Examining the role of transient receptor potential canonical 5 (TRPC5) in osteoarthritis
Introduction: Osteo-arthritis (OA) involves joint degradation and usually pain; with mechanisms poorly understood and few treatment options. There is evidence that the transient receptor potential canonical 5 (TRPC5) mRNA expression is reduced in OA patients’ synovia. Here we examine the profile of...
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Format: | Article |
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Elsevier
2020-12-01
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Series: | Osteoarthritis and Cartilage Open |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2665913120301199 |
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doaj-2c54f1ea129e4e75adabb9d90137596c |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
João de Sousa Valente Khadija M. Alawi Patrik Keringer Sabah Bharde Faseeha Ayaz Nurjahan Saleque Xenia Kodji Dibesh Thapa Fulye Argunhan Susan D. Brain |
spellingShingle |
João de Sousa Valente Khadija M. Alawi Patrik Keringer Sabah Bharde Faseeha Ayaz Nurjahan Saleque Xenia Kodji Dibesh Thapa Fulye Argunhan Susan D. Brain Examining the role of transient receptor potential canonical 5 (TRPC5) in osteoarthritis Osteoarthritis and Cartilage Open TRPC5 Osteoarthritis Inflammation Synovitis |
author_facet |
João de Sousa Valente Khadija M. Alawi Patrik Keringer Sabah Bharde Faseeha Ayaz Nurjahan Saleque Xenia Kodji Dibesh Thapa Fulye Argunhan Susan D. Brain |
author_sort |
João de Sousa Valente |
title |
Examining the role of transient receptor potential canonical 5 (TRPC5) in osteoarthritis |
title_short |
Examining the role of transient receptor potential canonical 5 (TRPC5) in osteoarthritis |
title_full |
Examining the role of transient receptor potential canonical 5 (TRPC5) in osteoarthritis |
title_fullStr |
Examining the role of transient receptor potential canonical 5 (TRPC5) in osteoarthritis |
title_full_unstemmed |
Examining the role of transient receptor potential canonical 5 (TRPC5) in osteoarthritis |
title_sort |
examining the role of transient receptor potential canonical 5 (trpc5) in osteoarthritis |
publisher |
Elsevier |
series |
Osteoarthritis and Cartilage Open |
issn |
2665-9131 |
publishDate |
2020-12-01 |
description |
Introduction: Osteo-arthritis (OA) involves joint degradation and usually pain; with mechanisms poorly understood and few treatment options. There is evidence that the transient receptor potential canonical 5 (TRPC5) mRNA expression is reduced in OA patients’ synovia. Here we examine the profile of TRPC5 in DRG and involvement in murine models of OA. Design: TRPC5 KO mice were subjected to partial meniscectomy (PMNX) or injected with monoiodoacetate (MIA) and pain-related behaviours were determined. Knee joint pathological scores were analysed and gene expression changes in ipsilateral synovium and dorsal root ganglia (DRG) determined. c-Fos protein expression in the ipsilateral dorsal horn of the spinal cord was quantified. Results: TRPC5 KO mice developed a discrete enhanced pain-related phenotype. In the MIA model, the pain-related phenotype correlated with c-Fos expression in the dorsal horn and increased expression of nerve injury markers ATF3, CSF1 and galanin in the ipsilateral DRG. There were negligible differences in the joint pathology between WT and TRPC5 KO mice, however detailed gene expression analysis determined increased expression of the mast cell marker CD117 as well as extracellular matrix remodelling proteinases MMP2, MMP13 and ADAMTS4 in MIA-treated TRPC5 KO mice. TRPC5 expression was defined to sensory subpopulations in DRG. Conclusions: Deletion of TRPC5 receptor signalling is associated with exacerbation of pain-like behaviour in OA which correlates with increased expression of enzymes involved in extracellular remodelling, inflammatory cells in the synovium and increased neuronal activation and injury in DRG. Together, these results identify a modulating role for TRPC5 in OA-induced pain-like behaviours. |
topic |
TRPC5 Osteoarthritis Inflammation Synovitis |
url |
http://www.sciencedirect.com/science/article/pii/S2665913120301199 |
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AT joaodesousavalente examiningtheroleoftransientreceptorpotentialcanonical5trpc5inosteoarthritis AT khadijamalawi examiningtheroleoftransientreceptorpotentialcanonical5trpc5inosteoarthritis AT patrikkeringer examiningtheroleoftransientreceptorpotentialcanonical5trpc5inosteoarthritis AT sabahbharde examiningtheroleoftransientreceptorpotentialcanonical5trpc5inosteoarthritis AT faseehaayaz examiningtheroleoftransientreceptorpotentialcanonical5trpc5inosteoarthritis AT nurjahansaleque examiningtheroleoftransientreceptorpotentialcanonical5trpc5inosteoarthritis AT xeniakodji examiningtheroleoftransientreceptorpotentialcanonical5trpc5inosteoarthritis AT dibeshthapa examiningtheroleoftransientreceptorpotentialcanonical5trpc5inosteoarthritis AT fulyeargunhan examiningtheroleoftransientreceptorpotentialcanonical5trpc5inosteoarthritis AT susandbrain examiningtheroleoftransientreceptorpotentialcanonical5trpc5inosteoarthritis |
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doaj-2c54f1ea129e4e75adabb9d90137596c2021-10-05T04:20:39ZengElsevierOsteoarthritis and Cartilage Open2665-91312020-12-0124100119Examining the role of transient receptor potential canonical 5 (TRPC5) in osteoarthritisJoão de Sousa Valente0Khadija M. Alawi1Patrik Keringer2Sabah Bharde3Faseeha Ayaz4Nurjahan Saleque5Xenia Kodji6Dibesh Thapa7Fulye Argunhan8Susan D. Brain9Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Cardiovascular Centre of Research Excellence, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UKSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Cardiovascular Centre of Research Excellence, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UKDepartment of Thermophysiology, Institute for Translational Medicine, Medical School, University of Pecs, 12 Szigeti Str., Pecs, H7624, HungarySection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Cardiovascular Centre of Research Excellence, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UKSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Cardiovascular Centre of Research Excellence, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UKSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Cardiovascular Centre of Research Excellence, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UKSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Cardiovascular Centre of Research Excellence, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UKSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Cardiovascular Centre of Research Excellence, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UKSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Cardiovascular Centre of Research Excellence, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UKSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Cardiovascular Centre of Research Excellence, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK; Corresponding author. Vascular Biology and Inflammation Section, Cardiovascular School of Medicine and Sciences, British Heart Foundation Centre of Excellence, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.Introduction: Osteo-arthritis (OA) involves joint degradation and usually pain; with mechanisms poorly understood and few treatment options. There is evidence that the transient receptor potential canonical 5 (TRPC5) mRNA expression is reduced in OA patients’ synovia. Here we examine the profile of TRPC5 in DRG and involvement in murine models of OA. Design: TRPC5 KO mice were subjected to partial meniscectomy (PMNX) or injected with monoiodoacetate (MIA) and pain-related behaviours were determined. Knee joint pathological scores were analysed and gene expression changes in ipsilateral synovium and dorsal root ganglia (DRG) determined. c-Fos protein expression in the ipsilateral dorsal horn of the spinal cord was quantified. Results: TRPC5 KO mice developed a discrete enhanced pain-related phenotype. In the MIA model, the pain-related phenotype correlated with c-Fos expression in the dorsal horn and increased expression of nerve injury markers ATF3, CSF1 and galanin in the ipsilateral DRG. There were negligible differences in the joint pathology between WT and TRPC5 KO mice, however detailed gene expression analysis determined increased expression of the mast cell marker CD117 as well as extracellular matrix remodelling proteinases MMP2, MMP13 and ADAMTS4 in MIA-treated TRPC5 KO mice. TRPC5 expression was defined to sensory subpopulations in DRG. Conclusions: Deletion of TRPC5 receptor signalling is associated with exacerbation of pain-like behaviour in OA which correlates with increased expression of enzymes involved in extracellular remodelling, inflammatory cells in the synovium and increased neuronal activation and injury in DRG. Together, these results identify a modulating role for TRPC5 in OA-induced pain-like behaviours.http://www.sciencedirect.com/science/article/pii/S2665913120301199TRPC5OsteoarthritisInflammationSynovitis |