The protective role of glucocerebrosidase/ceramide in rheumatoid arthritis

ABSTRACT

Objective

To clarify the role of glucocerebrosidase (GBA) and Ceramide (Cer) in rheumatoid arthritis (RA).

Methods

GBA-expressing lentivirus were constructed and injected into collagen-induced arthritis (CIA) mice, and compared with CIA mice injected with empty vector. The severity of arthritis and inflammatory mediators were evaluated. Fibroblast-like synoviocytes (FLS) from RA patients were transfected with GBA-expressing lentivirus, or pretreated with C6-Cer. The migration and invasion of FLS, the production of inflammatory cytokines, and the relevant signaling pathways were assessed.

Results

In CIA mice, GBA markedly improved arthritis compared to that in the CIA mice, with increased content of proteoglycan and integral cartilage surfaces and tidemarks. The circulating inflammatory mediators, including interleukin (IL)-1β, IL-6, IL-18, and matrix metalloproteinase (MMP)-1, were significantly reduced in CIA mice with GBA overexpression compared to those in CIA mice. GBA and C6-Cer treatment inhibited migration and invasion of FLS, and suppressed production of inflammatory cytokines and activation of the MAPK pathways.

Conclusion

GBA/Cer exhibited a protective role in CIA mice and RA FLS. These results highlight the potential of targeting GBA/Cer as a therapeutic strategy in RA and warrant further investigation.

KEYWORDS:

• Glucocerebrosidase
• ceramide
• collagen induced arthritis
• fibroblast-like synoviocytes
• rheumatoid arthritis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

The Ethics Committee of the Affiliated Hospital of Jiaxing University approved the procedures for the entire study (LS2018-051).

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This work was supported by the Natural Science Foundation of Zhejiang [grant numbers LY19H100002], and the 2019 Jiaxing Key Discipiline of Medcine, Rheumatology and Autoimmunology (Supporting Subject) 2019-zc-03;Key Projects of National Natural Science Foundation of Zhejiang Province;