ADSC-derived exosomes inhibit cbl-cathepsin K-dependent osteoclast activation in inflammatory arthritis

Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes joint inflammation and bone destruction due to increased osteoclast differentiation activity. Adipose-derived stem cells (ADSCs) are used treat tissue injury because they easy harvest exhibit immunomodulatory regenerative capacity. Previous studies demonstrated ADSC-derived exosomes (ADSC-Exo) protect articular cartilage from damage exert anti-inflammation effects. Thus, we investigated the underlying mechanisms of ADSC-Exo in regulating activation arthritis. RANKL TNF-family cytokine binds RANK required for mature osteoclasts. However, whether functionally involved inhibition formation via RANK-mediated signaling these pathological conditions unclear. Our data revealed ameliorated RA severity loss vivo inhibited differentiation, downstream signaling, NFATc1, cathepsin K, cbl-b. Moreover, could significantly suppress population RANKL-expressing TH17 cells. In brief, protects ameliorates gait abnormality CIA rats, which may be related RANK-signaling pathway As it relatively feasible obtain human adipose tissue, potential therapy RA. This study comprehensively understand effects on suppressing osteoclastogenesis. finding critical understanding homeostasis modulated by MSC-Exo provides biological evidence Supported grants Ministry Science Technology (111-2321-B-418-002, 111-2314-B-418-004), FEMH (2022-C-042 2022-C-123), NYCU-FEMH Cooperation (111DN12, 111DN22), NTUH-FEMH (111-FTN0012).