2. Academic Validation
  3. Purine metabolites promote ectopic new bone formation in ankylosing spondylitis

Purine metabolites promote ectopic new bone formation in ankylosing spondylitis

  • Int Immunopharmacol. 2023 Feb 10;116:109810. doi: 10.1016/j.intimp.2023.109810.
Shuqiong Zhang 1,  Zhidan Fan 2,  Zijun Ouyang 3,  Haiyan Sun 3,  Yue Song 4,  Haiguo Yu 2,  Qiang Xu 1,  Shijia Liu 5,  Yang Sun 6,  Fenli Shao 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China.
  • 2 Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, Jiangsu, China.
  • 3 School of Food And Drug, Institute of Marine Biomedicine, Shenzhen Polytechnic, 7098 Liuxian Avenue, Shenzhen, Guangdong 518055 China.
  • 4 Agilent Technologies Co. Ltd., Shanghai, China.
  • 5 Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, Jiangsu, China. Electronic address: shijialiu19@126.com.
  • 6 State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: yangsun@nju.edu.cn.
  • 7 State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China; College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: shaofenli90@163.com.
PMID: 36774858 DOI: 10.1016/j.intimp.2023.109810
Abstract

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 formation. 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.

Keywords

Ankylosing spondylitis; Chondrocytes; Ectopic new bone formation; Purine metabolites; SHP2.

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