Gregory James1, Kathleen A Sluka2, Linda Blomster1, Leanne Hall1, Annina B Schmid1,3, Cindy C Shu4, Christopher B Little4, James Melrose4,5, Paul W Hodges6. 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. 2. Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, IA, USA. 3. Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK. 4. 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. 5. Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia. 6. 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.
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. These slides can be retrieved under Electronic Supplementary Material.
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. These slides can be retrieved under Electronic Supplementary Material.
Authors: Paul W Hodges; Gregory James; Linda Blomster; Leanne Hall; Annina Schmid; Cindy Shu; Chris Little; James Melrose Journal: Spine (Phila Pa 1976) Date: 2015-07-15 Impact factor: 3.468
Authors: Paul W Hodges; Gregory James; Linda Blomster; Leanne Hall; Annina B Schmid; Cindy Shu; Chris Little; James Melrose Journal: Spine (Phila Pa 1976) Date: 2014-06-01 Impact factor: 3.468
Authors: Stephen H M Brown; Diane E Gregory; J Austin Carr; Samuel R Ward; Koichi Masuda; Richard L Lieber Journal: Spine (Phila Pa 1976) Date: 2011-10-01 Impact factor: 3.468
Authors: Gregory James; Linda Blomster; Leanne Hall; Annina B Schmid; Cindy C Shu; Christopher B Little; James Melrose; Paul W Hodges Journal: Spine (Phila Pa 1976) Date: 2016-08-01 Impact factor: 3.468
Authors: Damian Hoy; Lyn March; Peter Brooks; Fiona Blyth; Anthony Woolf; Christopher Bain; Gail Williams; Emma Smith; Theo Vos; Jan Barendregt; Chris Murray; Roy Burstein; Rachelle Buchbinder Journal: Ann Rheum Dis Date: 2014-03-24 Impact factor: 19.103
Authors: Gregory James; Carla Stecco; Linda Blomster; Leanne Hall; Annina B Schmid; Cindy C Shu; Christopher B Little; James Melrose; Paul W Hodges Journal: Eur Spine J Date: 2022-05-27 Impact factor: 2.721
Authors: Cindy C Shu; Andrew Dart; Robin Bell; Christina Dart; Elizabeth Clarke; Margaret M Smith; Christopher B Little; James Melrose Journal: JOR Spine Date: 2018-10-10
Authors: Robert Schleip; Paul William Hodges; Martina Zügel; Constantinos N Maganaris; Jan Wilke; Karin Jurkat-Rott; Werner Klingler; Scott C Wearing; Thomas Findley; Mary F Barbe; Jürgen Michael Steinacker; Andry Vleeming; Wilhelm Bloch Journal: Br J Sports Med Date: 2018-08-02 Impact factor: 13.800