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BioMed Research International
Volume 2013 (2013), Article ID 726581, 13 pages
http://dx.doi.org/10.1155/2013/726581
Research Article

Biological Activities of Phosphocitrate: A Potential Meniscal Protective Agent

1Department of Orthopedic Research Biology, Cannon Research, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA
2Dixon Advanced Analytics Group, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA

Received 18 March 2013; Revised 12 June 2013; Accepted 19 June 2013

Academic Editor: Toshihiro Nanki

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.

Abstract

Phosphocitrate (PC) inhibited meniscal calcification and the development of calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the mechanisms remain elusive. This study sought to examine the biological activities of PC in the absence of calcium crystals and test the hypothesis that PC is potentially a meniscal protective agent. We found that PC downregulated the expression of many genes classified in cell proliferation, ossification, prostaglandin metabolic process, and wound healing, including bloom syndrome RecQ helicase-like, cell division cycle 7 homolog, cell division cycle 25 homolog C, ankylosis progressive homolog, prostaglandin-endoperoxide synthases-1/cyclooxygenase-1, and plasminogen activator urokinase receptor. In contrast, PC stimulated the expression of many genes classified in fibroblast growth factor receptor signaling pathway, collagen fibril organization, and extracellular structure organization, including fibroblast growth factor 7, collagen type I, alpha 1, and collagen type XI, alpha 1. Consistent with its effect on the expression of genes classified in cell proliferation, collagen fibril organization, and ossification, PC inhibited the proliferation of OA meniscal cells and meniscal cell-mediated calcification while stimulating the production of collagens. These findings indicate that PC is potentially a meniscal-protective agent and a disease-modifying drug for arthritis associated with severe meniscal degeneration.