Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis

Abstract WNT ligands can activate several signalling cascades of pivotal importance during development and regenerative processes. Their de-regulation has been associated with the onset of different diseases. Here we investigated the role of the WNT/Calcium Calmodulin Kinase II (CaMKII) pathway in o...

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Autores principales:	Giovanna Nalesso, Anne-Sophie Thorup, Suzanne Elizabeth Eldridge, Anna De Palma, Amanpreet Kaur, Kiran Peddireddi, Kevin Blighe, Sharmila Rana, Bryony Stott, Tonia Louise Vincent, Bethan Lynne Thomas, Jessica Bertrand, Joanna Sherwood, Antonella Fioravanti, Costantino Pitzalis, Francesco Dell’Accio
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4f50238f6e9a41a8bd45f631bc8299e2
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spelling	oai:doaj.org-article:4f50238f6e9a41a8bd45f631bc8299e22021-12-02T11:37:18ZCalcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis10.1038/s41598-021-82067-w2045-2322https://doaj.org/article/4f50238f6e9a41a8bd45f631bc8299e22021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82067-whttps://doaj.org/toc/2045-2322Abstract WNT ligands can activate several signalling cascades of pivotal importance during development and regenerative processes. Their de-regulation has been associated with the onset of different diseases. Here we investigated the role of the WNT/Calcium Calmodulin Kinase II (CaMKII) pathway in osteoarthritis. We identified Heme Oxygenase I (HMOX1) and Sox-9 as specific markers of the WNT/CaMKII signalling in articular chondrocytes through a microarray analysis. We showed that the expression of the activated form of CaMKII, phospho-CaMKII, was increased in human and murine osteoarthritis and the expression of HMOX1 was accordingly reduced, demonstrating the activation of the pathway during disease progression. To elucidate its function, we administered the CaMKII inhibitor KN93 to mice in which osteoarthritis was induced by resection of the anterior horn of the medial meniscus and of the medial collateral ligament in the knee joint. Pharmacological blockade of CaMKII exacerbated cartilage damage and bone remodelling. Finally, we showed that CaMKII inhibition in articular chondrocytes upregulated the expression of matrix remodelling enzymes alone and in combination with Interleukin 1. These results suggest an important homeostatic role of the WNT/CaMKII signalling in osteoarthritis which could be exploited in the future for therapeutic purposes.Giovanna NalessoAnne-Sophie ThorupSuzanne Elizabeth EldridgeAnna De PalmaAmanpreet KaurKiran PeddireddiKevin BligheSharmila RanaBryony StottTonia Louise VincentBethan Lynne ThomasJessica BertrandJoanna SherwoodAntonella FioravantiCostantino PitzalisFrancesco Dell’AccioNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giovanna Nalesso Anne-Sophie Thorup Suzanne Elizabeth Eldridge Anna De Palma Amanpreet Kaur Kiran Peddireddi Kevin Blighe Sharmila Rana Bryony Stott Tonia Louise Vincent Bethan Lynne Thomas Jessica Bertrand Joanna Sherwood Antonella Fioravanti Costantino Pitzalis Francesco Dell’Accio Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis
description	Abstract WNT ligands can activate several signalling cascades of pivotal importance during development and regenerative processes. Their de-regulation has been associated with the onset of different diseases. Here we investigated the role of the WNT/Calcium Calmodulin Kinase II (CaMKII) pathway in osteoarthritis. We identified Heme Oxygenase I (HMOX1) and Sox-9 as specific markers of the WNT/CaMKII signalling in articular chondrocytes through a microarray analysis. We showed that the expression of the activated form of CaMKII, phospho-CaMKII, was increased in human and murine osteoarthritis and the expression of HMOX1 was accordingly reduced, demonstrating the activation of the pathway during disease progression. To elucidate its function, we administered the CaMKII inhibitor KN93 to mice in which osteoarthritis was induced by resection of the anterior horn of the medial meniscus and of the medial collateral ligament in the knee joint. Pharmacological blockade of CaMKII exacerbated cartilage damage and bone remodelling. Finally, we showed that CaMKII inhibition in articular chondrocytes upregulated the expression of matrix remodelling enzymes alone and in combination with Interleukin 1. These results suggest an important homeostatic role of the WNT/CaMKII signalling in osteoarthritis which could be exploited in the future for therapeutic purposes.
format	article
author	Giovanna Nalesso Anne-Sophie Thorup Suzanne Elizabeth Eldridge Anna De Palma Amanpreet Kaur Kiran Peddireddi Kevin Blighe Sharmila Rana Bryony Stott Tonia Louise Vincent Bethan Lynne Thomas Jessica Bertrand Joanna Sherwood Antonella Fioravanti Costantino Pitzalis Francesco Dell’Accio
author_facet	Giovanna Nalesso Anne-Sophie Thorup Suzanne Elizabeth Eldridge Anna De Palma Amanpreet Kaur Kiran Peddireddi Kevin Blighe Sharmila Rana Bryony Stott Tonia Louise Vincent Bethan Lynne Thomas Jessica Bertrand Joanna Sherwood Antonella Fioravanti Costantino Pitzalis Francesco Dell’Accio
author_sort	Giovanna Nalesso
title	Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis
title_short	Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis
title_full	Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis
title_fullStr	Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis
title_full_unstemmed	Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis
title_sort	calcium calmodulin kinase ii activity is required for cartilage homeostasis in osteoarthritis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4f50238f6e9a41a8bd45f631bc8299e2
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Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis

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