A role for TNFα in intervertebral disc degeneration: A non-recoverable catabolic shift

This study examines the effect of TNF alpha 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 alpha 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 beta-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNF alpha treatment. Control or TNF alpha cultures were assessed at 7 and 21 days; the 21 day group also included a recovery group with 7 days TNF alpha followed by 14 days in basal media. TNF alpha 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 alpha increased aggrecan degradation products and suggests increased beta-galactosidase staining at 21 days without any recovery. TNF alpha treatment of whole bovine discs for 7 days induced changes similar to the degeneration processes that occur in human IDD: aggrecan degradation, increased catabolism, proinflammatory cytokines and nerve growth factor expression. TNF alpha 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. (c) 2013 Elsevier Inc. All rights reserved.