PMID- 32887644
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20220531
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 22
IP  - 1
DP  - 2020 Sep 4
TI  - PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-kappaB 
      signaling.
PG  - 201
LID - 10.1186/s13075-020-02304-x [doi]
LID - 201
AB  - OBJECTIVES: A role for the type II arginine methyltransferase PRMT5 in various 
      human diseases has been identified. In this study, the potential mechanism 
      underlying the involvement of PRMT5 in the pathological process leading to 
      osteoarthritis (OA) was investigated. METHODS: PRMT5 expression in cartilage 
      tissues from patients with OA and control individuals was assessed by 
      immunohistochemical staining. The regulatory and functional roles of PRMT5 in the 
      chondrocytes of patients with OA and control individuals were determined by 
      western blotting and reverse transcription polymerase chain reaction. The effects 
      of the PRMT5 inhibitor EPZ on interleukin-1beta-induced inflammation were examined 
      in the chondrocytes of patients with OA and in the destabilized medial meniscus 
      (DMM) of a mouse model of OA. RESULTS: PRMT5 was specifically upregulated in the 
      cartilage of patients with OA. Moreover, adenovirus-mediated overexpression of 
      PRMT5 in human chondrocytes caused cartilage degeneration. This degeneration was 
      induced by elevated expression levels of matrix-degrading enzymes (matrix 
      metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13)) in 
      chondrocytes. The activation of the MAPK and nuclear factor kappaB signaling pathways 
      was evidenced by elevated levels of p-p65, p-p38, and p-JNK. These effects were 
      attenuated by inhibiting the expression of PRMT5. In the mouse model, EPZ 
      inhibited PRMT5 expression, thus protecting mouse cartilage from DMM-induced OA. 
      CONCLUSIONS: Our results demonstrate that PRMT5 is a crucial regulator of OA 
      pathogenesis, implying that EPZ has therapeutic value in the treatment of this 
      cartilage-destroying disease.
FAU - Dong, Yonghui
AU  - Dong Y
AD  - Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Henan University People's Hospital, No.7, Weiwu 
      Road, Zhengzhou, 450003, Henan Province, China.
FAU - Wang, Ping
AU  - Wang P
AD  - Department of pathophysiology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou, 450001, China.
AD  - Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou 
      University, Henan Cancer Hospital, Zhengzhou, 450008, China.
FAU - Yang, Yongguang
AU  - Yang Y
AD  - Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Henan University People's Hospital, No.7, Weiwu 
      Road, Zhengzhou, 450003, Henan Province, China.
FAU - Huang, Jincheng
AU  - Huang J
AD  - Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Henan University People's Hospital, No.7, Weiwu 
      Road, Zhengzhou, 450003, Henan Province, China.
FAU - Dai, Zhipeng
AU  - Dai Z
AD  - Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Henan University People's Hospital, No.7, Weiwu 
      Road, Zhengzhou, 450003, Henan Province, China.
FAU - Zheng, Wendi
AU  - Zheng W
AD  - Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Henan University People's Hospital, No.7, Weiwu 
      Road, Zhengzhou, 450003, Henan Province, China.
FAU - Li, Zhen
AU  - Li Z
AD  - Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Henan University People's Hospital, No.7, Weiwu 
      Road, Zhengzhou, 450003, Henan Province, China.
FAU - Yao, Zheng
AU  - Yao Z
AD  - Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Henan University People's Hospital, No.7, Weiwu 
      Road, Zhengzhou, 450003, Henan Province, China.
FAU - Zhang, Hongjun
AU  - Zhang H
AD  - Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Henan University People's Hospital, No.7, Weiwu 
      Road, Zhengzhou, 450003, Henan Province, China.
FAU - Zheng, Jia
AU  - Zheng J
AUID- ORCID: 0000-0002-0248-4307
AD  - Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou 
      University People's Hospital, Henan University People's Hospital, No.7, Weiwu 
      Road, Zhengzhou, 450003, Henan Province, China. zhengjia90180@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200904
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - EC 2.1.1.319 (PRMT5 protein, human)
RN  - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)
SB  - IM
MH  - *Cartilage, Articular/metabolism
MH  - Cells, Cultured
MH  - Chondrocytes/metabolism
MH  - Humans
MH  - Inflammation
MH  - Interleukin-1beta
MH  - NF-kappa B/metabolism
MH  - *Osteoarthritis/genetics
MH  - Protein-Arginine N-Methyltransferases/genetics
MH  - Signal Transduction
PMC - PMC7650297
OTO - NOTNLM
OT  - Chondrocytes
OT  - DMM model
OT  - Kinases
OT  - Osteoarthritis
OT  - PRMT5
COIS- The authors have no competing interests to declare.
EDAT- 2020/09/06 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/09/04
CRDT- 2020/09/05 05:15
PHST- 2020/02/29 00:00 [received]
PHST- 2020/08/25 00:00 [accepted]
PHST- 2020/09/05 05:15 [entrez]
PHST- 2020/09/06 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/09/04 00:00 [pmc-release]
AID - 10.1186/s13075-020-02304-x [pii]
AID - 2304 [pii]
AID - 10.1186/s13075-020-02304-x [doi]
PST - epublish
SO  - Arthritis Res Ther. 2020 Sep 4;22(1):201. doi: 10.1186/s13075-020-02304-x.