Proinflammatory cytokines and chemokine production and expression by human osteoblasts isolated from patients with rheumatoid arthritis and osteoarthritis

J Rheumatol. 1999 Apr;26(4):791-9.


Objective: To evaluate whether subchondral osteoblasts (OB) are involved in the production of cytokines and chemokines in rheumatic diseases.

Methods: OB were isolated from subchondral bone of rheumatoid arthritis (RA), osteoarthritis (OA) and post-traumatic (PT) patients, cultured in vitro in the presence or absence of interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), and assessed for the production, immunolocalization, and mRNA expression of proinflammatory cytokines (IL-1alpha, IL-1beta, TNF-alpha) and alpha and beta chemokines [IL-8, growth related gene product (GRO-alpha), monocyte chemoattractant protein 1 (MCP-1), RANTES, and macrophage inflammatory proteins MIP-1alpha, MIP-1beta].

Results: Cultured OB from different patients did not release IL-1alpha, IL-1beta, or TNF-alpha, and constitutively secreted IL-8, GRO-alpha, and MCP-1, while RANTES, MIP-1alpha, MIP-1beta were undetectable or near the lower level of sensitivity of the immunoenzymatic assay. GRO-alpha was significantly higher in RA than in OA and PT patients. IL-1beta and TNF-alpha alone or in combination strongly stimulated chemokine release by OB. Only RANTES production was not increased by the combination of the 2 cytokines. IL-1alpha, IL-1beta, and TNF-alpha were expressed as cytoplasmic proteins and were not secreted by OB even after stimulation.

Conclusion: OB from subchondral bone release chemokines that could be involved in the mechanisms that directly or indirectly cause bone remodelling and cartilage destruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Arthroplasty, Replacement, Hip
  • Biomarkers / analysis
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Chemokines / biosynthesis*
  • Chemokines / genetics
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • DNA Primers / chemistry
  • Drug Synergism
  • Female
  • Femur Head / injuries
  • Femur Head / metabolism
  • Femur Head / surgery
  • Humans
  • Interleukin-1 / pharmacology
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Osteoblasts / pathology
  • RNA / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / pharmacology


  • Biomarkers
  • Chemokines
  • Cytokines
  • DNA Primers
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • RNA