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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Funding

PWH has a Senior Principal Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1002190). The study was funded by a NHMRC Program Grant (ID631717) and Project Grant (APP1004032). The funding source did not play a role in investigation.

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Authors and Affiliations

  1. Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, QLD, 4072, Australia

    Gregory James, Linda Blomster, Leanne Hall, Annina B. Schmid & Paul W. Hodges

  2. Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, IA, USA

    Kathleen A. Sluka

  3. 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

    Cindy C. Shu, Christopher B. Little & James Melrose

  4. Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia

    James Melrose

  5. Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK

    Annina B. Schmid

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  1. Gregory James
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  2. Kathleen A. Sluka
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Correspondence to Paul W. Hodges.

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Conflict of interest

Outside of this study, Kathleen A. Sluka recieved research funding from Medtronic, Inc, consultancy fees from Bayer Inc. and a book honorarium from IASP Press. The other authors declare they have no conflicts of interest.

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James, G., Sluka, K.A., Blomster, L. et al. Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury. Eur Spine J 27, 1744–1756 (2018). https://doi.org/10.1007/s00586-018-5652-7

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