Interleukin-6, IL-6 receptor, and IL-6 nuclear factor gene expression in Paget's disease

J Bone Miner Res. 1994 Jan;9(1):75-80. doi: 10.1002/jbmr.5650090111.


The cytokine interleukin-6 (IL-6) is considered an important regulator of bone cell function and may play a central role in bone disease states characterized by increased bone remodeling, such as Paget's disease. Indeed, recent in vitro data suggest that IL-6 may be an autocrine/paracrine factor for pagetic osteoclasts. However, its expression and role in vivo are not known. Using in situ hybridization we investigated the spatial localization of expression of IL-6, IL-6 receptor (IL-6R), and the transcription factor (NF-IL-6) in pagetic bone. Our results show that osteoblasts in the normal remodeling bone of osteoarthritis (controls) and in Paget's disease express IL-6, IL-6R, and NF-IL-6 genes with higher levels of IL-6 and IL-6R mRNA in pagetic bone. Osteoclasts in both osteoarthritic and pagetic bone express IL-6R mRNA and NF-IL-6, but only pagetic osteoclasts expressed IL-6, suggesting that in Paget's disease IL-6 can act as an autocrine factor on osteoclasts. These results provide evidence for a major role of the IL-6 regulatory pathway in the phenotype of the pagetic osteoclasts and lead us to suggest a model linking possible paramyxovirus infection and IL-6 regulation in the pagetic osteoclast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Remodeling
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Gene Expression
  • Humans
  • In Situ Hybridization
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics*
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Osteitis Deformans / genetics
  • Osteitis Deformans / metabolism*
  • Osteitis Deformans / pathology
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Osteoblasts / metabolism*
  • Osteoclasts / metabolism
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin-6
  • Respirovirus / physiology


  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Interleukin-6
  • Nuclear Proteins
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-6