Upregulation of c-Fos protooncogene expression in pagetic osteoclasts


  • Judith Hoyland,

    1. Bone Disease Research Centre, Department of Pathological Sciences, University of Manchester, Manchester, England
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  • Paul T. Sharpe Ph.D.

    Corresponding author
    1. Bone Disease Group, Department of Craniofacial Development, United Medical and Dental School, Guy's Hospital, London, England
    • Department of Craniofacial Development UMDS Guy's Hospital London Bridge London SE1 9RT, UK
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Using in situ hybridization we show that expression of the c-fos oncogene, a gene normally associated with osteosarcomas, is greatly elevated in osteoclasts of patients with Paget's disease. Immunohistochemical staining with c-fos antibodies also shows increased protein in pagetic osteoclasts. In light of transgenic mouse experiments showing a key role for c-fos in bone resorption, we propose that elevated c-fos gene expression in pagetic osteoclasts is an important component in producing the pagetic phenotype. Levels of c-fos gene and protein expression in pagetic osteoblasts are lower than those detected in osteoclasts but still higher than in nonpagetic osteoblasts. This may provide an explanation for the increased incidence of osteosarcomas in patients with Paget's disease because overexpression of c-fos in osteoblasts of transgenic mice induces osteosarcoma formation.