title: Intraarticular corticosteroids decrease synovial RANKL expression in inflammatory arthritis.
abstract: OBJECTIVE
  Intraarticular corticosteroids are frequently used as successful adjuvant therapy for inflammatory arthritides, but little is known about their effects on molecules that regulate bone biology. We undertook this study to investigate the effect of intraarticular corticosteroids on the synovial expression of RANKL and osteoprotegerin (OPG).
  
  
  METHODS
  We evaluated RANKL, OPG, and surface marker expression by immunohistochemical methods in synovial knee biopsy samples obtained from 13 patients with inflammatory arthritis before and 2 weeks following intraarticular injection of triamcinolone hexacetonide. We further investigated the effect of dexamethasone (DEX) on RANKL expression by lymphocytes from rheumatoid arthritis synovial fluids (RA SF), using flow cytometric analysis. Finally, we evaluated the in vitro effect of DEX on RANKL and OPG expression in osteoblast-like cells, by Western blotting.
  
  
  RESULTS
  Intraarticular corticosteroids induced a decrease in the number of synovial T cells without influencing the number of macrophages, evaluated as both CD68+ and CD163+ cells. This change was paralleled by a decrease of synovial RANKL expression with a concomitant reduction of the RANKL:OPG ratio. DEX down-regulated RANKL expression on lymphocytes derived from RA SF. Moreover, in vitro pretreatment of osteoblast-like cells with tumor necrosis factor favored an antiresorptive effect of DEX treatment through a similar down-regulation of RANKL expression.
  
  
  CONCLUSIONS
  The decrease in inflammation attributed to intraarticular corticosteroids is accompanied by down-modulation of bone destruction markers. These findings offer a rationale for the beneficial effect of corticosteroids on joint erosion in arthritis.
authors.affiliation: Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Makrygiannakis
authors.forename: Erik
authors.initials: E
authors.lastname: af Klint
authors.forename: Sergiu-Bogdan
authors.initials: SB
authors.lastname: Catrina
authors.forename: Ileana Ruxandra
authors.initials: IR
authors.lastname: Botusan
authors.forename: Elin
authors.initials: E
authors.lastname: Klareskog
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Ulfgren
authors.forename: Anca Irinel
authors.initials: AI
authors.lastname: Catrina
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001168:Arthritis / Q000188:drug therapy* / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007270:Injections, Intra-Articular; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D014222:Triamcinolone Acetonide; C005900:triamcinolone hexacetonide