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BioMed Research International
Volume 2013, Article ID 326267, 11 pages
Research Article

Phosphocitrate Is Potentially a Disease-Modifying Drug for Noncrystal-Associated Osteoarthritis

1Department of Orthopedic Surgery, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA
2Department of Biostatistics, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA

Received 18 December 2012; Accepted 10 January 2013

Academic Editor: Andre Van Wijnen

Copyright © 2013 Yubo Sun et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Phosphocitrate (PC), a calcification inhibitor, inhibits the development of crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms underlying its disease-modifying effect remain elusive. This study sought to test the hypothesis that PC has calcium crystal-independent biological activities which are, at least in part, responsible for its disease-modifying activity. We found that PC inhibited the proliferation of OA fibroblast-like synoviocytes in the absence of calcium crystals. Consistent with its effect on cell proliferation, PC downregulated the expression of numerous genes classified in cell proliferation. PC also downregulated the expression of many genes classified in angiogenesis and inflammatory response including prostaglandin-endoperoxide synthase 2, interleukin-1 receptor, type I, and chemokine (C-C motif) ligand 2. In contrast, PC upregulated the expression of many genes classified in musculoskeletal tissue development, including aggrecan, type I collagen, and insulin-like growth factor binding protein 5. These findings suggest that PC is not only a promising disease-modifying drug for crystal-associated OA but also for noncrystal-associated OA.