Ms Lepus and Drs. Song and Wang contributed equally to this work.
Brief Report: Carboxypeptidase B Serves as a Protective Mediator in Osteoarthritis
Article first published online: 30 DEC 2013
Copyright © 2014 by the American College of Rheumatology
Arthritis & Rheumatology
Volume 66, Issue 1, pages 101–106, January 2014
How to Cite
Lepus, C. M., Song, J. J., Wang, Q., Wagner, C. A., Lindstrom, T. M., Chu, C. R., Sokolove, J., Leung, L. L. and Robinson, W. H. (2014), Brief Report: Carboxypeptidase B Serves as a Protective Mediator in Osteoarthritis. Arthritis & Rheumatology, 66: 101–106. doi: 10.1002/art.38213
- Issue published online: 30 DEC 2013
- Article first published online: 30 DEC 2013
- Accepted manuscript online: 7 OCT 2013 12:32PM EST
- Manuscript Accepted: 24 SEP 2013
- Manuscript Received: 24 JUN 2013
- VA Research Rehabilitation and Development award
- NIH. Grant Numbers: National Institute of Allergy and Infectious Diseases grant R01-AI-085268, National Heart, Lung, and Blood Institute Proteomics Center grant N01-HV-00242
- Stanford Medical Scientist Training Program
- Basic Science Research Program through the National Research Foundation of Korea. Grant Number: 2012R1A1A2005003
- Ministry of Education, Science, and Technology
- VA Career Development award
We previously demonstrated that carboxypeptidase B (CPB) protects against joint erosion in rheumatoid arthritis by inactivating complement component C5a. We also found that levels of CPB are abnormally high in the synovial fluid of individuals with another joint disease, osteoarthritis (OA). We undertook this study to investigate whether CPB plays a role in the pathogenesis of OA.
We compared the development of OA in CPB-deficient (Cpb2–/–) mice and wild-type mice by subjecting them to medial meniscectomy and histologically assessing cartilage damage, osteophyte formation, and synovitis in the stifle joints 4 months later. We measured levels of proCPB, proinflammatory cytokines, and complement components in synovial fluid samples from patients with symptomatic and radiographic knee OA. Finally, we used enzyme-linked immunosorbent assay, flow cytometry, and hemolytic assays to assess the effect of CPB on formation of membrane attack complex (MAC)–a complement effector critical to OA pathogenesis.
Cpb2–/– mice developed dramatically greater cartilage damage than did wild-type mice (P < 0.01) and had a greater number of osteophytes (P < 0.05) and a greater degree of synovitis (P < 0.05). In synovial fluid samples from OA patients, high levels of proCPB were associated with high levels of proinflammatory cytokines and complement components, and levels of proCPB correlated positively with those of MAC. In in vitro complement activation assays, activated CPB suppressed the formation of MAC as well as MAC-induced hemolysis.
Our data suggest that CPB protects against inflammatory destruction of the joints in OA, at least in part by inhibiting complement activation.