Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury

Gregory James; Kathleen A Sluka; Linda Blomster; Leanne Hall; Annina B Schmid; Cindy C Shu; Christopher B Little; James Melrose; Paul W Hodges

doi:10.1007/s00586-018-5652-7

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Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury

Journal article

Peer reviewed

Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury

Gregory James, Kathleen A Sluka, Linda Blomster, Leanne Hall, Annina B Schmid, Cindy C Shu, Christopher B Little, James Melrose and Paul W Hodges

European spine journal, Vol.27(8), pp.1744-1756

08/2018

DOI: 10.1007/s00586-018-5652-7

PMID: 29948327

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Abstract

Intervertebral disk (IVD) lesion and its subsequent degeneration have a profound effect on the multifidus muscle. The subacute/early chronic phase of multifidus remodeling after IVD lesion has been proposed to be regulated by inflammatory processes. The balance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages plays an important role in maintaining tissue integrity after injury. The localization, polarization of macrophage subtypes and their mediation of the pro-inflammatory cytokine tumor necrosis factor (TNF) are unknown in paraspinal muscles during IVD degeneration. A sheep model of IVD degeneration was used to investigate the role of macrophages and TNF in the structural alterations that occur within the multifidus muscle. Anterolateral lesions were induced at L3-4 IVD in sheep. Multifidus muscle tissue at L4 was harvested 3 and 6 months after lesion and used for immunofluorescence assays to examine total macrophage number, macrophage polarization between M1 and M2, and to assess the localization of TNF expression in muscle, adipose and connective tissues from injured and naïve control animals. A greater proportion of M1 macrophages is present in muscle at both 3 and 6 months after IVD lesion, and adipose tissue at 6 months. Total number of macrophages is unchanged. At 6 months, expression of TNF is increased in adipose and connective tissue and the proportion of TNF expressed by M1 macrophages is increased. These data support the proposal that macrophages and TNF (pro-inflammatory cytokine) play an active role in the subacute/early chronic phase of remodeling in muscle, adipose and connective tissues of the multifidus during IVD degeneration. This presents a novel target for treatment. These slides can be retrieved under Electronic Supplementary Material.

Tumor Necrosis Factor-alpha - metabolism

Inflammation - pathology

Macrophages - pathology

Male

Paraspinal Muscles - metabolism

Intervertebral Disc Degeneration - pathology

Inflammation - metabolism

Macrophages - metabolism

Animals

Paraspinal Muscles - pathology

Fluorescent Antibody Technique

Sheep

Spatio-Temporal Analysis

Lumbar Vertebrae - pathology

Intervertebral Disc - pathology

Details

Title: Subtitle: Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury
Creators: Gregory James - Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, QLD, 4072, Australia
Kathleen A Sluka - Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, IA, USA
Linda Blomster - Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, QLD, 4072, Australia
Leanne Hall - Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, QLD, 4072, Australia
Annina B Schmid - Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK
Cindy C Shu - Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Institute of Bone and Joint Research, The Royal North Shore Hospital, University of Sydney, St Leonards, NSW, Australia
Christopher B Little - Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Institute of Bone and Joint Research, The Royal North Shore Hospital, University of Sydney, St Leonards, NSW, Australia
James Melrose - Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia
Paul W Hodges - Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, QLD, 4072, Australia. p.hodges@uq.edu.au
Resource Type: Journal article
Publication Details: European spine journal, Vol.27(8), pp.1744-1756
Publisher: Germany
DOI: 10.1007/s00586-018-5652-7
PMID: 29948327
ISSN: 0940-6719
eISSN: 1432-0932
Grant note: DOI: 10.13039/501100000925, name: National Health and Medical Research Council, award: APP1002190, ID631717, APP1004032
Language: English
Date published: 08/2018
Academic Unit: Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984070812802771

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