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Updated: Dec 10, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-κB signaling
Yonghui Dong1, Ping Wang2,3, Yongguang Yang1
1Department 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.
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-1β-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 κB 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.
Insights
The arginine methyltransferase PRMT5 is upregulated in osteoarthritis (OA) cartilage, driving cartilage degeneration. Inhibiting PRMT5 with EPZ shows therapeutic potential for treating this joint disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- The type II arginine methyltransferase, PRMT5, is implicated in various human diseases.
- Understanding PRMT5's role in osteoarthritis (OA) pathogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the mechanism by which PRMT5 contributes to OA pathology.
- To evaluate the therapeutic potential of a PRMT5 inhibitor in OA.
Main Methods:
- Assessed PRMT5 expression in human OA cartilage via immunohistochemistry.
- Determined PRMT5's functional role in chondrocytes using western blotting and RT-PCR.
- Examined the effect of PRMT5 inhibitor EPZ in OA chondrocytes and a mouse OA model.
Main Results:
- PRMT5 was significantly upregulated in OA cartilage.
- Overexpression of PRMT5 in chondrocytes led to cartilage degeneration by increasing matrix-degrading enzymes (MMP-3, MMP-13) and activating MAPK/NF-κB pathways.
- EPZ treatment attenuated PRMT5 expression and protected cartilage in a mouse OA model.
Conclusions:
- PRMT5 is a key regulator in OA pathogenesis.
- PRMT5 inhibition with EPZ demonstrates therapeutic promise for OA treatment.
