Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor.
Degenerated intervertebral disc has lost its normal architecture, and there are changes both in the nuclear and annular parts of the disc. Changes in cell shape, especially in the annulus fibrosus, have been reported. During degeneration the cells become more rounded, chondrocyte-like, whereas in the normal condition annular cells are more spindle shaped. These chondrocyte-like cells, often forming clusters, affect extracellular matrix turnover. In previous studies transforming growth factor beta (TGFbeta) -1 and -2, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been highlighted in herniated intervertebral disc tissue. In the present study the same growth factors are analysed immunohistochemically in degenerated intervertebral disc tissue. Disc material was obtained from 16 discs operated for painful degenerative disc disease. Discs were classified according to the Dallas Discogram Description. Different disc regions were analysed in parallel. As normal control disc tissue material from eight organ donors was used. Polyclonal antibodies against different growth factors and TGFbeta receptor type II were used, and the immunoreaction was detected by the avidin biotin complex method. All studied degenerated discs showed immunoreactivity for TGFbeta receptor type II and bFGF. Fifteen of 16 discs were immunopositive for TGFbeta-1 and -2, respectively, and none showed immunoreaction for PDGF. Immunopositivity was located in blood vessels and in disc cells. In the nucleus pulposus the immunoreaction was located almost exclusively in chondrocyte-like disc cells, whereas in the annular region this reaction was either in chondrocyte-like disc cells, often forming clusters, or in fibroblast-like disc cells. Chondrocyte-like disc cells were especially prevalent in the posterior disrupted area. In the anterior area of the annulus fibrosus the distribution was more even between these two cell types. bFGF was expressed in the anterior annulus fibrosus more often in chondrocyte-like disc cells than in fibroblast-like disc cells. Control discs showed cellular immunopositivity for only TGFbeta-1 and -2 and TGFbeta receptor type II . We suggest that growth factors create a cascade in intervertebral disc tissue, where they act and participate in cellular remodelling from the normal resting stage via disc degeneration to disc herniation.
Spine Research Unit, Department of Orthopaedics and Traumatology, University of Helsinki, Helsinki, Finland.
Jukka
J
Tolonen
Mats
M
Grönblad
Heikki
H
Vanharanta
Johanna
J
Virri
Richard D
RD
Guyer
Tapio
T
Rytömaa
Erkki O
EO
Karaharju
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D051445:Fibrocartilage / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D007405:Intervertebral Disc Displacement / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015415:Biomarkers; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors