KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats

Abstract Currently there is no effective treatment available for osteoarthritis (OA). We have recently developed Kyoto University Substances (KUSs), ATPase inhibitors specific for valosin-containing protein (VCP), as a novel class of medicine for cellular protection. KUSs suppressed intracellular AT...

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Autores principales:	Sachiko Iwai, Hanako O. Ikeda, Hisashi Mera, Kohei Nishitani, Motoo Saito, Akitaka Tsujikawa, Akira Kakizuka
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/385d47d11ced4801a4ef89eaadc81f38
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spelling	oai:doaj.org-article:385d47d11ced4801a4ef89eaadc81f382021-12-02T16:35:42ZKUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats10.1038/s41598-021-95173-62045-2322https://doaj.org/article/385d47d11ced4801a4ef89eaadc81f382021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95173-6https://doaj.org/toc/2045-2322Abstract Currently there is no effective treatment available for osteoarthritis (OA). We have recently developed Kyoto University Substances (KUSs), ATPase inhibitors specific for valosin-containing protein (VCP), as a novel class of medicine for cellular protection. KUSs suppressed intracellular ATP depletion, endoplasmic reticulum (ER) stress, and cell death. In this study, we investigated the effects of KUS121 on chondrocyte cell death. In cultured chondrocytes differentiated from ATDC5 cells, KUS121 suppressed the decline in ATP levels and apoptotic cell death under stress conditions induced by TNFα. KUS121 ameliorated TNFα-induced reduction of gene expression in chondrocytes, such as Sox9 and Col2α. KUS121 also suppressed ER stress and cell death in chondrocytes under tunicamycin load. Furthermore, intraperitoneal administration of KUS121 in vivo suppressed chondrocyte loss and proteoglycan reduction in knee joints of a monosodium iodoacetate-induced OA rat model. Moreover, intra-articular administration of KUS121 more prominently reduced the apoptosis of the affected chondrocytes. These results demonstrate that KUS121 protects chondrocytes from stress-induced cell death in vitro and in vivo, and indicate that KUS121 is a promising novel therapeutic agent to prevent the progression of OA.Sachiko IwaiHanako O. IkedaHisashi MeraKohei NishitaniMotoo SaitoAkitaka TsujikawaAkira KakizukaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sachiko Iwai Hanako O. Ikeda Hisashi Mera Kohei Nishitani Motoo Saito Akitaka Tsujikawa Akira Kakizuka KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats
description	Abstract Currently there is no effective treatment available for osteoarthritis (OA). We have recently developed Kyoto University Substances (KUSs), ATPase inhibitors specific for valosin-containing protein (VCP), as a novel class of medicine for cellular protection. KUSs suppressed intracellular ATP depletion, endoplasmic reticulum (ER) stress, and cell death. In this study, we investigated the effects of KUS121 on chondrocyte cell death. In cultured chondrocytes differentiated from ATDC5 cells, KUS121 suppressed the decline in ATP levels and apoptotic cell death under stress conditions induced by TNFα. KUS121 ameliorated TNFα-induced reduction of gene expression in chondrocytes, such as Sox9 and Col2α. KUS121 also suppressed ER stress and cell death in chondrocytes under tunicamycin load. Furthermore, intraperitoneal administration of KUS121 in vivo suppressed chondrocyte loss and proteoglycan reduction in knee joints of a monosodium iodoacetate-induced OA rat model. Moreover, intra-articular administration of KUS121 more prominently reduced the apoptosis of the affected chondrocytes. These results demonstrate that KUS121 protects chondrocytes from stress-induced cell death in vitro and in vivo, and indicate that KUS121 is a promising novel therapeutic agent to prevent the progression of OA.
format	article
author	Sachiko Iwai Hanako O. Ikeda Hisashi Mera Kohei Nishitani Motoo Saito Akitaka Tsujikawa Akira Kakizuka
author_facet	Sachiko Iwai Hanako O. Ikeda Hisashi Mera Kohei Nishitani Motoo Saito Akitaka Tsujikawa Akira Kakizuka
author_sort	Sachiko Iwai
title	KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats
title_short	KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats
title_full	KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats
title_fullStr	KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats
title_full_unstemmed	KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats
title_sort	kus121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/385d47d11ced4801a4ef89eaadc81f38
work_keys_str_mv	AT sachikoiwai kus121attenuatestheprogressionofmonosodiumiodoacetateinducedosteoarthritisinrats AT hanakooikeda kus121attenuatestheprogressionofmonosodiumiodoacetateinducedosteoarthritisinrats AT hisashimera kus121attenuatestheprogressionofmonosodiumiodoacetateinducedosteoarthritisinrats AT koheinishitani kus121attenuatestheprogressionofmonosodiumiodoacetateinducedosteoarthritisinrats AT motoosaito kus121attenuatestheprogressionofmonosodiumiodoacetateinducedosteoarthritisinrats AT akitakatsujikawa kus121attenuatestheprogressionofmonosodiumiodoacetateinducedosteoarthritisinrats AT akirakakizuka kus121attenuatestheprogressionofmonosodiumiodoacetateinducedosteoarthritisinrats
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KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats

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