title: Expression of phosphocitrate-targeted genes in osteoarthritis menisci.
abstract: Phosphocitrate (PC) inhibited calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms remain elusive. This study sought to determine PC targeted genes and the expression of select PC targeted genes in OA menisci to test hypothesis that PC exerts its disease modifying activity in part by reversing abnormal expressions of genes involved in OA. We found that PC downregulated the expression of numerous genes classified in immune response, inflammatory response, and angiogenesis, including chemokine (C-C motif) ligand 5, Fc fragment of IgG, low affinity IIIb receptor (FCGR3B), and leukocyte immunoglobulin-like receptor, subfamily B member 3 (LILRB3). In contrast, PC upregulated the expression of many genes classified in skeletal development, including collagen type II alpha1, fibroblast growth factor receptor 3 (FGFR3), and SRY- (sex determining region Y-) box 9 (SOX-9). Immunohistochemical examinations revealed higher levels of FCGR3B and LILRB3 and lower level of SOX-9 in OA menisci. These findings indicate that OA is a disease associated with immune system activation and decreased expression of SOX-9 gene in OA menisci. PC exerts its disease modifying activity on OA, at least in part, by targeting immune system activation and the production of extracellular matrix and selecting chondroprotective proteins.
authors.affiliation: Department of Orthopedic Surgery, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopedic Surgery, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Mauerhan
authors.affiliation: Molecular Biology Core, Cannon Research, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA.
authors.forename: Nury M
authors.initials: NM
authors.lastname: Steuerwald
authors.affiliation: Department of Orthopedic Surgery, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Ingram
authors.affiliation: Department of Orthopedic Surgery, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kneisl
authors.affiliation: Department of Orthopedic Surgery, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Hanley
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis*; D002118:Calcium / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects; D002951:Citrates / Q000008:administration & dosage; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D008592:Menisci, Tibial / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010003:Osteoarthritis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000096:biosynthesis*; D017452:Receptors, IgG / Q000096:biosynthesis*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D055758:SOX9 Transcription Factor / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; D002951:Citrates; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C527699:LILRB3 protein, human; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D055758:SOX9 Transcription Factor; C014148:phosphocitrate; D003094:Collagen; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; D002118:Calcium