Intraarticular corticosteroids decrease synovial RANKL expression in inflammatory arthritis

Arthritis Rheum. 2006 May;54(5):1463-72. doi: 10.1002/art.21767.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage*
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / administration & dosage*
  • Arthritis / drug therapy*
  • Arthritis / metabolism*
  • Carrier Proteins / biosynthesis*
  • Cells, Cultured
  • Female
  • Glycoproteins / biosynthesis*
  • Humans
  • Injections, Intra-Articular
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Middle Aged
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / biosynthesis*
  • Receptors, Tumor Necrosis Factor / biosynthesis*
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology
  • Triamcinolone Acetonide / administration & dosage
  • Triamcinolone Acetonide / analogs & derivatives*


  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Carrier Proteins
  • Glycoproteins
  • Membrane Glycoproteins
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Triamcinolone Acetonide
  • triamcinolone hexacetonide