Biological activities of phosphocitrate: a potential meniscal protective agent.
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.
Department of Orthopedic Research Biology, Cannon Research, Carolinas Medical Center, Charlotte, NC 28232, USA. yubo.sun@carolinas.org
Yubo
Y
Sun
Andrea
A
Roberts
David R
DR
Mauerhan
Andrew R
AR
Sun
H James
HJ
Norton
Edward N
EN
Hanley
D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002951:Citrates / Q000008:administration & dosage*; D003094:Collagen / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007592:Joint Diseases / Q000378:metabolism / Q000473:pathology; D007719:Knee Joint / Q000378:metabolism; D008592:Menisci, Tibial / Q000187:drug effects / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011453:Prostaglandins / Q000235:genetics / Q000378:metabolism; D014652:Vascular Diseases / Q000378:metabolism / Q000473:pathology
D002951:Citrates; D011453:Prostaglandins; C014148:phosphocitrate; D003094:Collagen; D002118:Calcium