Bone-protective effects of neutralizing angiopoietin-like protein 4 monoclonal antibody in rheumatoid arthritis

ABSTRACT: Despite recent advances, rheumatoid arthritis (RA) patients remain refractory to therapy. Dysregulated overproduction of angiopoietin-like 4 protein (ANGPTL4) is thought to be contributed to the disease development. Therefore, interference with ANGPTL4 biological function may constitute a new therapeutic strategy for this disease. ANGPTL4 was initially identified as a regulator of lipid metabolism, which is hydrolyzed to N-terminal (nANGPTL4) and C-terminal (cANGPTL4) fragments in vivo. cANGPTL4 is involved in several non-lipid-related processes, including angiogenesis and inflammation. In this study, we analyzed the mRNA expression of ANGPTL4 in synovial tissue of RA in comparison to healthy individuals of the Gene Expression Omnibus (GEO) database. The results indicated that the mRNA expression of ANGPTL4 is increased in RA synovial tissues. The level of ANGPTL4 was found to be overexpressed in the sera and synovial tissues from patients with RA versus controls. A neutralizing antibody against cANGPTL4 (anti-cANGPTL4 Ab) was employed to treat arthritis animal models, including collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA), respectively. The results demonstrated that the anti-cANGPTL4 Ab inhibited inflammation and bone loss in two models. Transcriptomic and proteomic profiling of synovial tissues from AIA model indicated that the anti-cANGPTL4 Ab inhibited fibroblast-like synoviocyte (FLS) immigration and inflammatory-induced osteoclastogenesis. These data collectively identify ANGPTL4 as a potential biomarker for the diagnosis of RA, and targeting cANGPTL4 may represent a novel therapeutic strategy.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Wenxiang Cheng  

PROVIDER: PXD055569 | iProX | Thu Sep 05 00:00:00 BST 2024

REPOSITORIES: iProX