Interleukin-6, IL-6 receptor, and IL-6 nuclear factor gene expression in Paget's disease.
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.
Hoyland
J A
JA
Department of Osteoarticular Pathology, Medical School, University of Manchester, England.
Freemont
A J
AJ
Sharpe
P T
PT
D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D010001:Osteitis Deformans / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics*; D019947:Receptors, Interleukin-6; D018108:Respirovirus / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6