title: Oncoprotein c-Fos and c-Jun immunopositive cells and cell clusters in herniated intervertebral disc tissue.
abstract: The oncoproteins c-Fos and c-Jun create a transcriptional site early response activating protein (AP-1) mediating the regulation of gene expression in response to extracellular signalling by, for example, cytokines. These proteins are important in the signalling pathway from the cell membrane to the nucleus. Previously, oncoproteins have been located in articular synovium and in chondrocytes, participating in transcription. There is, however, no such study of intervertebral disc tissue. In disc degeneration and after herniation, cell proliferation markers have been demonstrated. In the present study we visualize the AP-1 transcriptional site factors c-Fos and c-Jun in 38 human herniated intervertebral disc tissue samples by immunohistochemical staining with monoclonal antibodies. No immunoreactivity could be observed in control disc tissue, indicating that after herniation, disc cells are entering from the resting stage to the cell cycle. Furthermore, c-Jun immunoreactivity was also observed in disc cell clusters, thus demonstrating them to be active transcriptional sites in disc tissue. c-Fos immunoreactivity was seen in 15/38 and c-Jun in 28/38 herniated discs (39% and 74% respectively). Immunopositive groups of disc cells were noted in 7/28 (25%) of the oncoprotein-immunopositive samples. We did not see any difference in immunoreactivity between female and male patients. Furthermore, we did not notice any statistical difference regarding the immunoreaction for proto-oncogenes c-Fos and c-Jun in extrusions, sequesters and protrusions. Nor did immunostaining show any significant relationship with preoperative pain duration. We concluded that, in herniated disc tissue, the oncoproteins c-Fos and c-Jun are activated in disc cells and cell clusters. In the future, learning more about this transcriptional signal pathway may result in new specific treatments for intervertebral disc pathology.
authors.affiliation: Research Laboratory, Spine Research Unit, Department of Orthopaedics and Traumatology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Tolonen
authors.forename: Mats
authors.initials: M
authors.lastname: Grönblad
authors.forename: Johanna
authors.initials: J
authors.lastname: Virri
authors.forename: Seppo
authors.initials: S
authors.lastname: Seitsalo
authors.forename: Tapio
authors.initials: T
authors.lastname: Rytömaa
authors.forename: Erkki
authors.initials: E
authors.lastname: Karaharju
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001416:Back Pain / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007405:Intervertebral Disc Displacement / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012727:Sex Characteristics; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D015415:Biomarkers; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun