Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice

Abstract Runx2 may play an important role in development of osteoarthritis (OA). However, the specific role of Runx2 in articular chondrocyte function and in OA development in adult mice has not been fully defined. In this study, we performed the destabilization of the medial meniscus (DMM) surgery...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lifan Liao, Shanxing Zhang, Jianhong Gu, Takeshi Takarada, Yukio Yoneda, Jian Huang, Lan Zhao, Chun-do Oh, Jun Li, Baoli Wang, Meiqing Wang, Di Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/599c91f9147140b096f48826257dbaab
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:599c91f9147140b096f48826257dbaab
record_format	dspace
spelling	oai:doaj.org-article:599c91f9147140b096f48826257dbaab2021-12-02T15:05:39ZDeletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice10.1038/s41598-017-02490-w2045-2322https://doaj.org/article/599c91f9147140b096f48826257dbaab2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02490-whttps://doaj.org/toc/2045-2322Abstract Runx2 may play an important role in development of osteoarthritis (OA). However, the specific role of Runx2 in articular chondrocyte function and in OA development in adult mice has not been fully defined. In this study, we performed the destabilization of the medial meniscus (DMM) surgery at 12-week-old mice to induce OA in adult Runx2 Agc1CreER mice, in which Runx2 was specifically deleted in Aggrecan-expressing chondrocytes by administering tamoxifen at 8-weeks of age. Knee joint samples were collected 8- and 12-weeks post-surgery and analyzed through histology, histomorphometry and micro-computed tomography (μCT). Our results showed that severe OA-like defects were observed after DMM surgery in Cre-negative control mice, including articular cartilage degradation and subchondral sclerosis, while the defects were significantly ameliorated in Runx2 Agc1CreER KO mice. Immunohistochemical (IHC) results showed significantly reduced expression of MMP13 in Runx2 Agc1CreER KO mice compared to that in Cre-negative control mice. Results of quantitative reverse-transcription PCR (qRT-PCR) demonstrated that expression of the genes encoding for matrix degradation enzymes was significantly decreased in Runx2 Agc1CreER KO mice. Thus, our findings suggest that inhibition of Runx2 in chondrocytes could at least partially rescue DMM-induced OA-like defects in adult mice.Lifan LiaoShanxing ZhangJianhong GuTakeshi TakaradaYukio YonedaJian HuangLan ZhaoChun-do OhJun LiBaoli WangMeiqing WangDi ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lifan Liao Shanxing Zhang Jianhong Gu Takeshi Takarada Yukio Yoneda Jian Huang Lan Zhao Chun-do Oh Jun Li Baoli Wang Meiqing Wang Di Chen Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice
description	Abstract Runx2 may play an important role in development of osteoarthritis (OA). However, the specific role of Runx2 in articular chondrocyte function and in OA development in adult mice has not been fully defined. In this study, we performed the destabilization of the medial meniscus (DMM) surgery at 12-week-old mice to induce OA in adult Runx2 Agc1CreER mice, in which Runx2 was specifically deleted in Aggrecan-expressing chondrocytes by administering tamoxifen at 8-weeks of age. Knee joint samples were collected 8- and 12-weeks post-surgery and analyzed through histology, histomorphometry and micro-computed tomography (μCT). Our results showed that severe OA-like defects were observed after DMM surgery in Cre-negative control mice, including articular cartilage degradation and subchondral sclerosis, while the defects were significantly ameliorated in Runx2 Agc1CreER KO mice. Immunohistochemical (IHC) results showed significantly reduced expression of MMP13 in Runx2 Agc1CreER KO mice compared to that in Cre-negative control mice. Results of quantitative reverse-transcription PCR (qRT-PCR) demonstrated that expression of the genes encoding for matrix degradation enzymes was significantly decreased in Runx2 Agc1CreER KO mice. Thus, our findings suggest that inhibition of Runx2 in chondrocytes could at least partially rescue DMM-induced OA-like defects in adult mice.
format	article
author	Lifan Liao Shanxing Zhang Jianhong Gu Takeshi Takarada Yukio Yoneda Jian Huang Lan Zhao Chun-do Oh Jun Li Baoli Wang Meiqing Wang Di Chen
author_facet	Lifan Liao Shanxing Zhang Jianhong Gu Takeshi Takarada Yukio Yoneda Jian Huang Lan Zhao Chun-do Oh Jun Li Baoli Wang Meiqing Wang Di Chen
author_sort	Lifan Liao
title	Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice
title_short	Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice
title_full	Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice
title_fullStr	Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice
title_full_unstemmed	Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice
title_sort	deletion of runx2 in articular chondrocytes decelerates the progression of dmm-induced osteoarthritis in adult mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/599c91f9147140b096f48826257dbaab
work_keys_str_mv	AT lifanliao deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT shanxingzhang deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT jianhonggu deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT takeshitakarada deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT yukioyoneda deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT jianhuang deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT lanzhao deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT chundooh deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT junli deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT baoliwang deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT meiqingwang deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice AT dichen deletionofrunx2inarticularchondrocytesdeceleratestheprogressionofdmminducedosteoarthritisinadultmice
_version_	1718388765595009024

Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice

Ejemplares similares