A role for TNF? in intervertebral disc degeneration: a non-recoverable catabolic shift.

ABSTRACT: This study examines the effect of TNF? on whole bovine intervertebral discs in organ culture and its association with changes characteristic of intervertebral disc degeneration (IDD) in order to inform future treatments to mitigate the chronic inflammatory state commonly found with painful IDD. Pro-inflammatory cytokines such as TNF? contribute to disc pathology and are implicated in the catabolic phenotype associated with painful IDD. Whole bovine discs were cultured to examine cellular (anabolic/catabolic gene expression, cell viability and senescence using ?-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNF? treatment. Control or TNF? cultures were assessed at 7 and 21 days; the 21 day group also included a recovery group with 7 days TNF? followed by 14 days in basal media. TNF? induced catabolic and anti-anabolic shifts in the nucleus pulposus (NP) and annulus fibrosus (AF) at 7 days and this persisted until 21 days however cell viability was not affected. Data indicates that TNF? increased aggrecan degradation products and suggests increased ?-galactosidase staining at 21 days without any recovery. TNF? treatment of whole bovine discs for 7 days induced changes similar to the degeneration processes that occur in human IDD: aggrecan degradation, increased catabolism, pro-inflammatory cytokines and nerve growth factor expression. TNF? significantly reduced anabolism in cultured IVDs and a possible mechanism may be associated with cell senescence. Results therefore suggest that successful treatments must promote anabolism and cell proliferation in addition to limiting inflammation.

SUBMITTER: Purmessur D 

PROVIDER: S-EPMC3640343 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature