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Changes in Nerve Growth Factor Expression and Macrophage Phenotype Following Intervertebral Disc Injury in Mice
Author(s) -
Nakawaki Mitsufumi,
Uchida Kentaro,
Miyagi Masayuki,
Inoue Gen,
Kawakubo Ayumu,
Satoh Masashi,
Takaso Masashi
Publication year - 2019
Publication title -
journal of orthopaedic research®
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.24308
Subject(s) - nerve growth factor , tumor necrosis factor alpha , macrophage , transforming growth factor , medicine , nerve injury , intervertebral disc , cytokine , pathology , proinflammatory cytokine , inflammation , endocrinology , biology , anatomy , anesthesia , in vitro , receptor , biochemistry
Nerve growth factor (NGF) is increased in intervertebral discs (IVDs) after disc injury and anti‐NGF therapy improves low back pain in humans. Furthermore, M1 and M2 macrophage subtypes play a role in degenerative IVD injury. We examined M1 and M2 macrophage markers and NGF and cytokine expression in IVD‐derived cells from control and IVD‐injured mice for 28 days following injury. Ngf messenger RNA (mRNA) expression was increased 1 day after injury in injured compared with control mice, and persisted for up to 28 days. Flow cytometric analysis demonstrated that the proportion of F4/80+ CD11b+ cells was significantly increased from 1 day after injury for up to 28 days in injured compared to control mice. mRNA expression of M1 macrophage markers Tnfa , Il1b , and Nos2 was significantly increased 1 day after injury in injured compared to control mice, before gradually decreasing. At 28 days, no significant difference was observed in M1 markers. The M2a marker, Ym1 , was significantly increased 1 day after injury in injured compared with control mice, while M2a and M2c markers Tgfb and Cd206 were significantly increased 7, 14, and 28 days after injury. Tumor necrosis factor α (TNF‐α) and transforming growth factor β (TGF‐β) stimulated Ngf mRNA and NGF protein expression in IVD cells. Our results suggest that TNF‐α and TGF‐β may stimulate NGF production under inflammatory and non‐inflammatory conditions following IVD injury. As TNF‐α and TGF‐β are produced by M1 and M2 macrophages, further investigations are needed to reveal the role of macrophages in NGF expression following IVD injury. Our results may aid in developing treatments for IVD‐related LBP pathology. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1798–1804, 2019