In vivo growth factor treatment of degenerated intervertebral discs.
METHODS
An in vivo model was used to investigate the response of degenerated discs to various exogenous growth factors.


OBJECTIVE
To study growth factor-induced alterations of the spatial and temporal patterns of disc cellularity and matrix gene expression.


BACKGROUND
Cell proliferation and proteoglycan synthesis have been stimulated by growth factors in normal disc cells, suggesting that growth factors may play a therapeutic role for degeneration. However, the response in situ in degenerated discs has not been characterized.


METHODS
Degeneration was induced in murine caudal discs by static compression. Degenerated discs were given single or multiple injections of growth and differentiation factor-5, transforming growth factor-beta, insulin-like growth factor-1, basic fibroblast growth factor, or saline as control. Comparisons of disc morphology, anular cell density, proliferating cells, disc height, and aggrecan and type II collagen gene expression were made either 1 week or 4 weeks after treatment.


RESULTS
In some growth and differentiation factor-5 and transforming growth factor-beta treated discs, expansion of inner anular fibrochondrocyte populations into the nucleus was observed. The cells actively expressed aggrecan and type II collagen mRNA. A lesser effect was observed for insulin-like growth factor-1 and little or no effect for basic fibroblast growth factor. Differences in cell density and proliferating cells were not significant between treatments but suggested a trend of increased cellularity and proliferation following growth factor treatment. A statistically significant increase in disc height 4 weeks after growth and differentiation factor-5 treatment was measured.


CONCLUSIONS
Anular fibrochondrocytes in degenerated discs are responsive to some growth factors in vivo. The results have implications in the early intervention of disc degeneration to arrest or slow the degenerative process.
Walsh
Andrew J L
AJ
Orthopaedic Bioengineering Laboratory, Department of Orthopaedic Surgery, University of California, San Francisco 94143-0514, USA.
Bradford
David S
DS
Lotz
Jeffrey C
JC
D053674:Aggrecans; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D024043:Collagen Type II / Q000235:genetics; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000627:therapeutic use*; D017403:In Situ Hybridization; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D007403:Intervertebral Disc / Q000187:drug effects* / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000473:pathology; D037181:Lectins, C-Type; D051379:Mice; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013623:Tail; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000627:therapeutic use; D016896:Treatment Outcome
C508320:Acan protein, mouse; D053674:Aggrecans; D019485:Bone Morphogenetic Proteins; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I