Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model

Abstract The catabolism of hyaluronan in articular cartilage remains unclear. The aims of this study were to investigate the effects of hyaluronidase 2 (Hyal2) knockdown in articular cartilage on the development of osteoarthritis (OA) using genetic manipulated mice. Destabilization of the medial men...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yoshitoshi Higuchi, Yoshihiro Nishida, Eiji Kozawa, Lisheng Zhuo, Eisuke Arai, Shunsuke Hamada, Daigo Morita, Kunihiro Ikuta, Koji Kimata, Takahiro Ushida, Naoki Ishiguro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/05e159b5fcb542dc9216288f24301a65
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:05e159b5fcb542dc9216288f24301a65
record_format	dspace
spelling	oai:doaj.org-article:05e159b5fcb542dc9216288f24301a652021-12-02T11:52:55ZConditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model10.1038/s41598-017-07376-52045-2322https://doaj.org/article/05e159b5fcb542dc9216288f24301a652017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07376-5https://doaj.org/toc/2045-2322Abstract The catabolism of hyaluronan in articular cartilage remains unclear. The aims of this study were to investigate the effects of hyaluronidase 2 (Hyal2) knockdown in articular cartilage on the development of osteoarthritis (OA) using genetic manipulated mice. Destabilization of the medial meniscus (DMM) model of Col2a promoter specific conditional Hyal2 knockout (Hyal −/− ) mice was established and examined. Age related and DMM induced alterations of articular cartilage of knee joint were evaluated with modified Mankin score and immunohistochemical staining of MMP-13, ADAMTS-5, KIAA11199, and biotinylated- hyaluronan binding protein staining in addition to histomorphometrical analyses. Effects of Hyal2 suppression were also analyzed using explant culture of an IL-1α induced articular cartilage degradation model. The amount and size of hyaluronan in articular cartilage were higher in Hyal2 −/− mice. Hyal2 −/− mice exhibited aggravated cartilage degradation in age-related and DMM induced mice. MMP-13 and ADAMTS-5 positive chondrocytes were significantly higher in Hyal2 −/− mice. Articular cartilage was more degraded in explant cultures obtained from Hyal2 −/− mice. Knockdown of Hyal2 in articular cartilage induced OA development and progression possibly mediated by an imbalance of HA metabolism. This suggests that Hyal2 knockdown exhibits mucopolysaccharidosis-like OA change in articular cartilage similar to Hyal1 knockdown.Yoshitoshi HiguchiYoshihiro NishidaEiji KozawaLisheng ZhuoEisuke AraiShunsuke HamadaDaigo MoritaKunihiro IkutaKoji KimataTakahiro UshidaNaoki IshiguroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshitoshi Higuchi Yoshihiro Nishida Eiji Kozawa Lisheng Zhuo Eisuke Arai Shunsuke Hamada Daigo Morita Kunihiro Ikuta Koji Kimata Takahiro Ushida Naoki Ishiguro Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model
description	Abstract The catabolism of hyaluronan in articular cartilage remains unclear. The aims of this study were to investigate the effects of hyaluronidase 2 (Hyal2) knockdown in articular cartilage on the development of osteoarthritis (OA) using genetic manipulated mice. Destabilization of the medial meniscus (DMM) model of Col2a promoter specific conditional Hyal2 knockout (Hyal −/− ) mice was established and examined. Age related and DMM induced alterations of articular cartilage of knee joint were evaluated with modified Mankin score and immunohistochemical staining of MMP-13, ADAMTS-5, KIAA11199, and biotinylated- hyaluronan binding protein staining in addition to histomorphometrical analyses. Effects of Hyal2 suppression were also analyzed using explant culture of an IL-1α induced articular cartilage degradation model. The amount and size of hyaluronan in articular cartilage were higher in Hyal2 −/− mice. Hyal2 −/− mice exhibited aggravated cartilage degradation in age-related and DMM induced mice. MMP-13 and ADAMTS-5 positive chondrocytes were significantly higher in Hyal2 −/− mice. Articular cartilage was more degraded in explant cultures obtained from Hyal2 −/− mice. Knockdown of Hyal2 in articular cartilage induced OA development and progression possibly mediated by an imbalance of HA metabolism. This suggests that Hyal2 knockdown exhibits mucopolysaccharidosis-like OA change in articular cartilage similar to Hyal1 knockdown.
format	article
author	Yoshitoshi Higuchi Yoshihiro Nishida Eiji Kozawa Lisheng Zhuo Eisuke Arai Shunsuke Hamada Daigo Morita Kunihiro Ikuta Koji Kimata Takahiro Ushida Naoki Ishiguro
author_facet	Yoshitoshi Higuchi Yoshihiro Nishida Eiji Kozawa Lisheng Zhuo Eisuke Arai Shunsuke Hamada Daigo Morita Kunihiro Ikuta Koji Kimata Takahiro Ushida Naoki Ishiguro
author_sort	Yoshitoshi Higuchi
title	Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model
title_short	Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model
title_full	Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model
title_fullStr	Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model
title_full_unstemmed	Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model
title_sort	conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/05e159b5fcb542dc9216288f24301a65
work_keys_str_mv	AT yoshitoshihiguchi conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel AT yoshihironishida conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel AT eijikozawa conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel AT lishengzhuo conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel AT eisukearai conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel AT shunsukehamada conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel AT daigomorita conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel AT kunihiroikuta conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel AT kojikimata conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel AT takahiroushida conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel AT naokiishiguro conditionalknockdownofhyaluronidase2inarticularcartilagestimulatesosteoarthriticprogressioninamicemodel
_version_	1718394906712473600

Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model

Ejemplares similares