Chondrocyte mTORC1 activation stimulates miR-483-5p via HDAC4 in osteoarthritis progression

Hua Wang, Haiyan Zhang, Qiuyi Sun, Jian Yang, Chun Zeng, Changhai Ding, Daozhang Cai, Anling Liu, Xiaochun Bai

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in chondrocytes has been shown to accelerate the severity of destabilization of the medial meniscus-induced and age-related osteoarthritis (OA) phenotypes with aberrant chondrocyte hypertrophy and angiogenesis. Meanwhile, we previously reported that miR-483-5p is essential for the initiation and development of OA by stimulating chondrocyte hypertrophy and angiogenesis. The connection between mTORC1 and miR-483-5p activation in OA progression, however, remains unclear. In this study, we elucidated their relationship and identified the underlying mechanisms. The expression of miR-483-5p in the articular cartilage of cartilage-specific TSC1 knockout mice was assessed compared with control mice using the Agilent Mouse miRNA (8*60K) V19.0 array and real-time polymerase chain reaction (RT-PCR). The functional effects of the stimulation of miR-483-5p via histone deacetylase 4 (HDAC4) by mTORC1 in OA development, subsequently modulating its downstream targets matrilin 3 and tissue inhibitor of metalloproteinase 2, were examined by immunostaining, western blotting, and real-time PCR. This study revealed that miR-483-5p was responsible for mTORC1 activation-stimulated OA. Mechanistically, mTORC1 controls the HDAC4-dependent expression of miR-483-5p to stimulate chondrocyte hypertrophy, extracellular matrix degradation, and subchondral bone angiogenesis, and it consequently initiates and accelerates the development of OA. Our findings revealed a novel mTORC1-HDAC4-miR-483-5p pathway that is critical for OA development.

Original languageEnglish (US)
Pages (from-to)2730-2740
Number of pages11
JournalJournal of Cellular Physiology
Volume234
Issue number3
DOIs
StatePublished - Mar 2019

Fingerprint

Histone Deacetylases
Chondrocytes
Osteoarthritis
Chemical activation
Hypertrophy
Real-Time Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinase-2
Tibial Meniscus
Polymerase chain reaction
Cartilage
Critical Pathways
MicroRNAs
Articular Cartilage
mechanistic target of rapamycin complex 1
Knockout Mice
Bone
Extracellular Matrix
Western Blotting
Degradation
Phenotype

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Wang, Hua ; Zhang, Haiyan ; Sun, Qiuyi ; Yang, Jian ; Zeng, Chun ; Ding, Changhai ; Cai, Daozhang ; Liu, Anling ; Bai, Xiaochun. / Chondrocyte mTORC1 activation stimulates miR-483-5p via HDAC4 in osteoarthritis progression. In: Journal of Cellular Physiology. 2019 ; Vol. 234, No. 3. pp. 2730-2740.
@article{76dc15a28fa242bba28e780557505dbe,
title = "Chondrocyte mTORC1 activation stimulates miR-483-5p via HDAC4 in osteoarthritis progression",
abstract = "The hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in chondrocytes has been shown to accelerate the severity of destabilization of the medial meniscus-induced and age-related osteoarthritis (OA) phenotypes with aberrant chondrocyte hypertrophy and angiogenesis. Meanwhile, we previously reported that miR-483-5p is essential for the initiation and development of OA by stimulating chondrocyte hypertrophy and angiogenesis. The connection between mTORC1 and miR-483-5p activation in OA progression, however, remains unclear. In this study, we elucidated their relationship and identified the underlying mechanisms. The expression of miR-483-5p in the articular cartilage of cartilage-specific TSC1 knockout mice was assessed compared with control mice using the Agilent Mouse miRNA (8*60K) V19.0 array and real-time polymerase chain reaction (RT-PCR). The functional effects of the stimulation of miR-483-5p via histone deacetylase 4 (HDAC4) by mTORC1 in OA development, subsequently modulating its downstream targets matrilin 3 and tissue inhibitor of metalloproteinase 2, were examined by immunostaining, western blotting, and real-time PCR. This study revealed that miR-483-5p was responsible for mTORC1 activation-stimulated OA. Mechanistically, mTORC1 controls the HDAC4-dependent expression of miR-483-5p to stimulate chondrocyte hypertrophy, extracellular matrix degradation, and subchondral bone angiogenesis, and it consequently initiates and accelerates the development of OA. Our findings revealed a novel mTORC1-HDAC4-miR-483-5p pathway that is critical for OA development.",
author = "Hua Wang and Haiyan Zhang and Qiuyi Sun and Jian Yang and Chun Zeng and Changhai Ding and Daozhang Cai and Anling Liu and Xiaochun Bai",
year = "2019",
month = "3",
doi = "10.1002/jcp.27088",
language = "English (US)",
volume = "234",
pages = "2730--2740",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "3",

}

Wang, H, Zhang, H, Sun, Q, Yang, J, Zeng, C, Ding, C, Cai, D, Liu, A & Bai, X 2019, 'Chondrocyte mTORC1 activation stimulates miR-483-5p via HDAC4 in osteoarthritis progression', Journal of Cellular Physiology, vol. 234, no. 3, pp. 2730-2740. https://doi.org/10.1002/jcp.27088

Chondrocyte mTORC1 activation stimulates miR-483-5p via HDAC4 in osteoarthritis progression. / Wang, Hua; Zhang, Haiyan; Sun, Qiuyi; Yang, Jian; Zeng, Chun; Ding, Changhai; Cai, Daozhang; Liu, Anling; Bai, Xiaochun.

In: Journal of Cellular Physiology, Vol. 234, No. 3, 03.2019, p. 2730-2740.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chondrocyte mTORC1 activation stimulates miR-483-5p via HDAC4 in osteoarthritis progression

AU - Wang, Hua

AU - Zhang, Haiyan

AU - Sun, Qiuyi

AU - Yang, Jian

AU - Zeng, Chun

AU - Ding, Changhai

AU - Cai, Daozhang

AU - Liu, Anling

AU - Bai, Xiaochun

PY - 2019/3

Y1 - 2019/3

N2 - The hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in chondrocytes has been shown to accelerate the severity of destabilization of the medial meniscus-induced and age-related osteoarthritis (OA) phenotypes with aberrant chondrocyte hypertrophy and angiogenesis. Meanwhile, we previously reported that miR-483-5p is essential for the initiation and development of OA by stimulating chondrocyte hypertrophy and angiogenesis. The connection between mTORC1 and miR-483-5p activation in OA progression, however, remains unclear. In this study, we elucidated their relationship and identified the underlying mechanisms. The expression of miR-483-5p in the articular cartilage of cartilage-specific TSC1 knockout mice was assessed compared with control mice using the Agilent Mouse miRNA (8*60K) V19.0 array and real-time polymerase chain reaction (RT-PCR). The functional effects of the stimulation of miR-483-5p via histone deacetylase 4 (HDAC4) by mTORC1 in OA development, subsequently modulating its downstream targets matrilin 3 and tissue inhibitor of metalloproteinase 2, were examined by immunostaining, western blotting, and real-time PCR. This study revealed that miR-483-5p was responsible for mTORC1 activation-stimulated OA. Mechanistically, mTORC1 controls the HDAC4-dependent expression of miR-483-5p to stimulate chondrocyte hypertrophy, extracellular matrix degradation, and subchondral bone angiogenesis, and it consequently initiates and accelerates the development of OA. Our findings revealed a novel mTORC1-HDAC4-miR-483-5p pathway that is critical for OA development.

AB - The hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) in chondrocytes has been shown to accelerate the severity of destabilization of the medial meniscus-induced and age-related osteoarthritis (OA) phenotypes with aberrant chondrocyte hypertrophy and angiogenesis. Meanwhile, we previously reported that miR-483-5p is essential for the initiation and development of OA by stimulating chondrocyte hypertrophy and angiogenesis. The connection between mTORC1 and miR-483-5p activation in OA progression, however, remains unclear. In this study, we elucidated their relationship and identified the underlying mechanisms. The expression of miR-483-5p in the articular cartilage of cartilage-specific TSC1 knockout mice was assessed compared with control mice using the Agilent Mouse miRNA (8*60K) V19.0 array and real-time polymerase chain reaction (RT-PCR). The functional effects of the stimulation of miR-483-5p via histone deacetylase 4 (HDAC4) by mTORC1 in OA development, subsequently modulating its downstream targets matrilin 3 and tissue inhibitor of metalloproteinase 2, were examined by immunostaining, western blotting, and real-time PCR. This study revealed that miR-483-5p was responsible for mTORC1 activation-stimulated OA. Mechanistically, mTORC1 controls the HDAC4-dependent expression of miR-483-5p to stimulate chondrocyte hypertrophy, extracellular matrix degradation, and subchondral bone angiogenesis, and it consequently initiates and accelerates the development of OA. Our findings revealed a novel mTORC1-HDAC4-miR-483-5p pathway that is critical for OA development.

UR - http://www.scopus.com/inward/record.url?scp=85052379739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052379739&partnerID=8YFLogxK

U2 - 10.1002/jcp.27088

DO - 10.1002/jcp.27088

M3 - Article

C2 - 30145794

AN - SCOPUS:85052379739

VL - 234

SP - 2730

EP - 2740

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 3

ER -