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

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Article number2371
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

Fingerprint

Tibial Meniscus
Chondrocytes
Osteoarthritis
Joints
Aggrecans
Articular Cartilage
Sclerosis
Tamoxifen
Knee Joint
Reverse Transcription
Histology
Tomography
Gene Expression
Polymerase Chain Reaction

ASJC Scopus subject areas

  • General

Cite this

Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice. / Liao, Lifan; Zhang, Shanxing; Gu, Jianhong; Takarada, Takeshi; Yoneda, Yukio; Huang, Jian; Zhao, Lan; Oh, Chun Do; Li, Jun; Wang, Baoli; Wang, Meiqing; Chen, Di.

In: Scientific Reports, Vol. 7, No. 1, 2371, 01.12.2017.

Research output: Contribution to journalArticle

Liao, L, Zhang, S, Gu, J, Takarada, T, Yoneda, Y, Huang, J, Zhao, L, Oh, CD, Li, J, Wang, B, Wang, M & Chen, D 2017, 'Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice', Scientific Reports, vol. 7, no. 1, 2371. https://doi.org/10.1038/s41598-017-02490-w
Liao, Lifan ; Zhang, Shanxing ; Gu, Jianhong ; Takarada, Takeshi ; Yoneda, Yukio ; Huang, Jian ; Zhao, Lan ; Oh, Chun Do ; Li, Jun ; Wang, Baoli ; Wang, Meiqing ; Chen, Di. / Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
@article{cf058b3810084d249503de7f161bc653,
title = "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 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.",
author = "Lifan Liao and Shanxing Zhang and Jianhong Gu and Takeshi Takarada and Yukio Yoneda and Jian Huang and Lan Zhao and Oh, {Chun Do} and Jun Li and Baoli Wang and Meiqing Wang and Di Chen",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-02490-w",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice

AU - Liao, Lifan

AU - Zhang, Shanxing

AU - Gu, Jianhong

AU - Takarada, Takeshi

AU - Yoneda, Yukio

AU - Huang, Jian

AU - Zhao, Lan

AU - Oh, Chun Do

AU - Li, Jun

AU - Wang, Baoli

AU - Wang, Meiqing

AU - Chen, Di

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85019957125&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019957125&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-02490-w

DO - 10.1038/s41598-017-02490-w

M3 - Article

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 2371

ER -