TNFα transport induced by dynamic loading alters biomechanics of intact intervertebral discs.
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 &amp; 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 &amp; aggrecan degradation), biomechanical behavior (Creep, Recovery &amp; 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 TNFα removal. TNFα exposure induced changes in IVD biomechanics (reduced diurnal displacements &amp; increased dynamic stiffness).


CONCLUSIONS
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.
Leni & Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai, New York, NY, United States of America; Department of Biomedical Engineering, The City College of New York, New York, NY, United States of America.
Benjamin A
BA
Walter
Leni & Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Morakot
M
Likhitpanichkul
Leni & Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Svenja
S
Illien-Junger
Shriners Hospital for Children, Montreal QC, Canada.
Peter J
PJ
Roughley
Leni & Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Andrew C
AC
Hecht
Leni & Peter W. May Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
James C
JC
Iatridis
D000818:Animals; D002417:Cattle; D016207:Cytokines / Q000378:metabolism; D055119:Elastic Modulus; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D009924:Organ Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016207:Cytokines; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha