title: Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc.
abstract: Low back pain (LBP) is a common, debilitating and economically important disorder. Current evidence implicates loss of intervertebral disc (IVD) matrix consequent upon 'degeneration' as a major cause of LBP. Degeneration of the IVD involves increases in degradative enzymes and decreases in the extracellular matrix (ECM) component in a process that is controlled by a range of cytokines and growth factors. Studies have suggested using anabolic growth factors to regenerate the normal matrix of the IVD, hence restoring disc height and reversing degenerative disc disease. However, for such therapies to be successful it is vital that the target cells (i.e. the disc cells) express the appropriate receptors. This immunohistochemical study has for the first time investigated the expression and localization of four potentially beneficial growth factor receptors (i.e. TGFbetaRII, BMPRII, FGFR3 and IGFRI) in non-degenerate and degenerate human IVDs. Receptor expression was quantified across regions of the normal and degenerate disc and showed that cells of the nucleus pulposus (NP) and inner annulus fibrosus (IAF) expressed significantly higher levels of the four growth factor receptors investigated. There were no significant differences between the four growth factor expression in non-degenerate and degenerate biopsies. However, expression of TGFbetaRII, FGFR3 and IGFRI, but not BMP RII, were observed in the ingrowing blood vessels that characterize part of the disease aetiology. In conclusion, this study has demonstrated the expression of the four growth factor receptors at similar levels in the chondrocyte-like cells of the NP and IAF in both non-degenerate and degenerate discs, implicating a role in normal disc homeostasis and suggesting that the application of these growth factors to the degenerate human IVD would stimulate matrix production. However, the expression of some of the growth factor receptors on ingrowing blood vessels might be problematic in a therapeutic approach.
authors.affiliation: Division of Laboratory and Regenerative Medicine, School of Medicine, Stopford Building, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Le Maitre
authors.forename: Stephen M A
authors.initials: SM
authors.lastname: Richardson
authors.forename: Pauline
authors.initials: P
authors.lastname: Baird
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Freemont
authors.forename: Judith A
authors.initials: JA
authors.lastname: Hoyland
mesh_terms: D000328:Adult; D000368:Aged; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000502:physiology; D017116:Low Back Pain / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D017978:Receptors, Growth Factor / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012038:Regeneration; D013122:Spinal Diseases / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017526:Receptor, IGF Type 1; D017346:Protein Serine-Threonine Kinases; D052006:Bone Morphogenetic Protein Receptors, Type II; D000077294:Receptor, Transforming Growth Factor-beta Type II