TNF alpha Transport Induced by Dynamic Loading Alters Biomechanics of Intact Intervertebral Discs

• Authors: Benjamin A. Walter, Icahn School of Medicine at Mount Sinai; Morakat Likhitpanichkul, Icahn School of Medicine at Mount Sinai; Svenja Illien-Junger, Emory University; Peter J. Roughley, Shriners Hospital for Children; Andrew C. Hecht, Icahn School of Medicine at Mount Sinai; James C. Iatridis, Icahn School of Medicine at Mount Sinai
• Journal Title: PLoS ONE
• Volume: Volume 10, Number 3
• Publisher: Public Library of Science | 2015-03-03, Pages e0118358-e0118358
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0118358
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; EARLY DEGENERATIVE CHANGES; NECROSIS-FACTOR-ALPHA; ORGAN-CULTURE SYSTEM; FACET JOINT INJURY; GENE-EXPRESSION; AGGRECAN DEGRADATION; SPINAL-CORD; MODEL; COMPRESSION; CATABOLISM

Abstract

Objective: Intervertebral disc (IVD) degeneration is an important contributor to the development of back pain, and a key factor relating pain and degeneration are the presence of pro-inflammatory cytokines and IVD motion. There is surprisingly limited understanding of how mechanics and inflammation interact in the IVD. This study investigated interactions between mechanical loading and pro-inflammatory cytokines in a large animal organ culture model to address fundamental questions regarding (i.) how inflammatory mediators arise within the IVD, (ii.) how long inflammatory mediators persist, and (iii.) how inflammatory mediators influence IVD biomechanics. Methods: Bovine caudal IVDs were cultured for 6 or 20-days under static & dynamic loading with or without exogenous TNFα in the culture medium, simulating a consequence of inflammation of the surrounding spinal tissues. TNFα transport within the IVD was assessed via immunohistochemistry. Changes in IVD structural integrity (dimensions, histology & aggrecan degradation), biomechanical behavior (Creep, Recovery & Dynamic stiffness) and pro-inflammatory cytokines in the culture medium (ELISA) were assessed. Results: TNFα was able to penetrate intact IVDs when subjected to dynamic loading but not static loading. Once transported within the IVD, pro-inflammatory mediators persisted for 4-8 days after TNF α removal. TNFα exposure induced changes in IVD biomechanics (reduced diurnal displacements & increased dynamic stiffness). Discussion: This study demonstrated that exposure to TNFα, as might occur from injured surrounding tissues, can penetrate healthy intact IVDs, induce expression of additional pro-inflammatory cytokines and alter IVD mechanical behavior. We conclude that exposure to pro-inflammatory cytokine may be an initiating event in the progression of IVD degeneration in addition to being a consequence of disease.