Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis, characterized by synovitis and progressive destruction of bone and cartilage in the affected joints. 

Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are typically prescribed immediately after an RA diagnosis to minimize joint damage. However, some patients' poor response to standard treatments highlights the urgent need for new therapies.

In a study published in Molecular Therapy, a research team led by Dr. CHENG Wenxiang from the Shenzhen Institutes of Advanced Technology of the Chinese Academy of Sciences, along with the collaborators, discovered that overexpression of Angiopoietin-like protein 4 (ANGPTL4) is a characteristic of RA patients, and that neutralizing the C-terminal fragments of ANGPTL4 reduces the severity of arthritis in animal models.

Researchers demonstrated elevated ANGPTL4 expression levels in the sera and synovial tissues of RA patients, as well as animal models of collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA). In CIA and AIA animal models, they found that administering an anti-cANGPTL4 antibody to neutralize part of ANGPTL4 led to reduced severity and inhibited inflammatory processes, and that treatment with anti-cANGPTL4 antibody inhibited bone destruction.

Mechanistic studies showed that anti-cANGPTL4 antibody reduced inflammation in the fibroblast-like synoviocytes by modulating the SIRT1/NF-κB pathway. Furthermore, the anti-cANGPTL4 antibody was shown to mitigate RANKL-induced osteoclastogenesis. 

The findings of this study suggested that the anti-cANGPTL4 antibody inhibits the invasion and migration of fibroblast-like synoviocytes, thereby suppressing osteoclast activation.

"Our work not only identifies a potential valuable biomarker for monitoring the progression of RA, but also offers a promising approach for its effective treatment," said by Dr. CHENG.