title: A role for TNFα in intervertebral disc degeneration: a non-recoverable catabolic shift.
abstract: This study examines the effect of TNFα 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 TNFα 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 β-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNFα treatment. Control or TNFα cultures were assessed at 7 and 21 days; the 21 day group also included a recovery group with 7 days TNFα followed by 14 days in basal media. TNFα 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 TNFα increased aggrecan degradation products and suggests increased β-galactosidase staining at 21 days without any recovery. TNFα 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. TNFα 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.
authors: Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors: D
authors: D
authors: Purmessur
authors: B A
authors: BA
authors: Walter
authors: P J
authors: PJ
authors: Roughley
authors: D M
authors: DM
authors: Laudier
authors: A C
authors: AC
authors: Hecht
authors: James
authors: J
authors: Iatridis
mesh_terms: D000818:Animals; D002417:Cattle; D002470:Cell Survival; D016922:Cellular Senescence; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D007403:Intervertebral Disc / Q000473:pathology / Q000503:physiopathology; D055959:Intervertebral Disc Degeneration / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009924:Organ Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha