Purine metabolites promote ectopic new bone formation in ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that mainly affects the axial skeleton, whose typical features are inflammatory back pain, bone structural damage and pathological new bone forma-tion. The pathology of ectopic new bone formation is still little known. In this study, we found increased purine metabolites in plasma of patients with AS. Similarly, metabolome analysis indicated increased purine metabolites in both serum of CD4-Cre; Ptpn11fl/fl and SHP2-deficient chondrocytes. SHP2-deficient chondrocytes promoted the growth of wild type chondrocytes and differentiation of osteoblasts in CD4-Cre; Ptpn11fl/fl mice, which spontaneously developed AS-like bone disease. Purine metabolites, along with PTHrP derived from SHP2-deficient chondrocytes, accelerated the growth of chondrocytes and ectopic new bone formation through PKA/CREB signaling. Moreover, Suramin, a purinergic receptor antagonist, suppressed pathological new bone formation in AS-like bone disease. Overall, these results highlight the potential role of targeting purinergic signaling in retarding ectopic new bone formation in AS.

Automated summary

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that mainly affects the axial skeleton and is characterized by inflammatory back pain, bone structural damage, and pathological new bone formation. This study found increased purine metabolites in the plasma of AS patients and SHP2-deficient chondrocytes, suggesting the potential role of purinergic signaling in promoting ectopic new bone formation. Targeting purinergic signaling, specifically using the purinergic receptor antagonist Suramin, could potentially suppress pathological new bone formation in AS-like bone disease.