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PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-?B signaling.

ABSTRACT: 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-1?-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 ?B 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.

SUBMITTER: Dong Y

PROVIDER: S-EPMC7650297 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-κB signaling.

Dong Yonghui Y Wang Ping P Yang Yongguang Y Huang Jincheng J Dai Zhipeng Z Zheng Wendi W Li Zhen Z Yao Zheng Z Zhang Hongjun H Zheng Jia J

Arthritis research & therapy 20200904 1

<h4>Objectives</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 32887644

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PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-?B signaling.

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PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-κB signaling.

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