Targeting osteoclast-derived DPP4 alleviates inflammation-mediated ectopic bone formation in ankylosing spondylitis

Area of Science:

• Immunology
• Rheumatology
• Bone Biology

Background:

• Ankylosing spondylitis (AS) is a chronic inflammatory condition marked by abnormal bone growth.
• The role of dipeptidyl peptidase-4 (DPP4) in bone metabolism is known, but its effect on AS remains unexplored.

Purpose of the Study:

• To investigate DPP4 levels in AS patients.
• To evaluate the therapeutic efficacy of a DPP4 inhibitor in an experimental AS model.
• To explore the in vitro effects of DPP4 inhibition on osteoclast differentiation.

Main Methods:

• DPP4 levels were measured in serum, synovial fluid, and facet joint tissue of AS patients.
• A DPP4 inhibitor was administered to curdlan-injected SKG mice, a model for AS.
• Clinical scores, micro-CT imaging, and in vitro osteoclast precursor cell assays were performed.

Main Results:

• DPP4 levels were elevated in AS patients' serum and synovial fluid.
• DPP4 inhibitor treatment reduced arthritis scores, enthesitis, and inflammation-induced bone loss in mice.
• Inhibition of DPP4 decreased osteoclast differentiation and related markers in vitro.

Conclusions:

• DPP4 inhibition may offer a novel therapeutic strategy for AS.
• Targeting DPP4 could mitigate inflammation-mediated ectopic bone formation in ankylosing spondylitis.