Intervertebral disc and macrophage interaction induces mechanical hyperalgesia and cytokine production in a herniated disc model in rats

Takada, Toru; Nishida, Kotaro; Maeno, Kazuo; Kakutani, Kenichiro; Yurube, Takashi; Doita, Minoru; Kurosaka, Masahiro

doi:10.1002/art.34456

Cited by 65 publications

(75 citation statements)

References 50 publications

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“…An increase in expression of some cytokines and MMPs in herniated IVD may occur when molecules seen as 'non-self' by immune cells become exposed. This may also be linked to the phenomenon of spontaneous regression or disappearance of extruded IVD fragments, which has been attributed to matrix degradation and phagocytosis by recruited/infiltrated macrophages [102][103][104][105][106]. In cases with transligamentous extrusion, which can occur when the NP is potentially more exposed to immune cells, regression occurs [107].…”

Section: Mmp19mentioning

confidence: 99%

Inflammation in intervertebral disc degeneration and regeneration

Molinos

Almeida

Caldeira

et al. 2015

J. R. Soc. Interface.

336

256

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Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players.

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Section: Mmp19mentioning

confidence: 99%

Inflammation in intervertebral disc degeneration and regeneration

Molinos

Almeida

Caldeira

et al. 2015

J. R. Soc. Interface.

336

256

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“…10,32,65 An in vitro study that investigated the ability of HA and the polysulfated polysaccharide pentosan polysulfate (PPS) to promote chondrogenic differentiation of MPCs in culture found that HA over a concentration range of 2.5-20 m/ml inhibited MPC chondrogenesis rather than promoted it. 19 In contrast, PPS markedly stimulated MPC chondrogenic differentiation and also promoted cell proliferation, reduced MPC apoptosis, and inhibited osteogenic differentiation.…”

mentioning

confidence: 99%

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

Oehme

Ghosh

Goldschlager

et al. 2016

SPI

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OBJECTIVE Disc degeneration and associated low-back pain are major causes of suffering and disability. The authors examined the potential of mesenchymal precursor cells (MPCs), when formulated with pentosan polysulfate (PPS), to ameliorate disc degeneration in an ovine model. METHODS Twenty-four sheep had annular incisions made at L2–3, L3–4, and L4–5 to induce degeneration. Twelve weeks after injury, the nucleus pulposus of a degenerated disc in each animal was injected with ProFreeze and PPS formulated with either a low dose (0.1 million MPCs) or a high dose (0.5 million MPCs) of cells. The 2 adjacent injured discs in each spine were either injected with PPS and ProFreeze (PPS control) or not injected (nil-injected control). The adjacent noninjured L1–2 and L5–6 discs served as noninjured control discs. Disc height indices (DHIs) were obtained at baseline, before injection, and at planned death. After necropsy, 24 weeks after injection, the spines were subjected to MRI and morphological, histological, and biochemical analyses. RESULTS Twelve weeks after the annular injury, all the injured discs exhibited a significant reduction in mean DHI (low-dose group 17.19%; high-dose group 18.01% [p < 0.01]). Twenty-four weeks after injections, the discs injected with the low-dose MPC+PPS formulation recovered disc height, and their mean DHI was significantly greater than the DHI of PPS- and nil-injected discs (p < 0.001). Although the mean Pfirrmann MRI disc degeneration score for the low-dose MPC+PPS–injected discs was lower than that for the nil- and PPS-injected discs, the differences were not significant. The disc morphology scores for the nil- and PPS-injected discs were significantly higher than the normal control disc scores (p < 0.005), whereas the low-dose MPC+PPS–injected disc scores were not significantly different from those of the normal controls. The mean glycosaminoglycan content of the nuclei pulposus of the low-dose MPC+PPS–injected discs was significantly higher than that of the PPS-injected controls (p < 0.05) but was not significantly different from the normal control disc glycosaminoglycan levels. Histopathology degeneration frequency scores for the low-dose MPC+PPS–injected discs were lower than those for the PPS- and Nil-injected discs. The corresponding high-dose MPC+PPS–injected discs failed to show significant improvements in any outcome measure relative to the controls. CONCLUSIONS Intradiscal injections of a formulation composed of 0.1 million MPCs combined with PPS resulted in positive effects in reducing the progression of disc degeneration in an ovine model, as assessed by improvements in DHI and morphological, biochemical, and histopathological scores.

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“…Previous studies have demonstrated that when the IVD was relocated in vivo, the autografts induced TNF-α and IL-1β mRNA upregulation, rapidly followed by macrophage infiltration (25). The phosphorylation of p38 MAPK, an important component of the MAPK family, was closely associated with the secretion and accumulation of proinflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

p38 mitogen-activated protein kinase inhibition modulates nucleus pulposus cell apoptosis in spontaneous resorption of herniated intervertebral discs: An experimental study in rats

Zhu

Liu

Yang

et al. 2016

Molecular Medicine Reports

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Abstract. The present study was performed to investigate the role of p38 mitogen-activated protein kinase (MAPK) in the resorption of herniated intervertebral discs in 30 rats. In the non-contained and p38 MAPK inhibition (p38i) groups, two coccygeal intervertebral discs (IVDs) were removed and wounded prior to relocation into the subcutaneous space of the skin of the back. In the contained group, the cartilage endplates maintained their integrity. Furthermore, SB203580 was injected intraperitoneally into the p38i group, whereas saline was injected into the other two groups. In the non-contained group, the weight of the relocated IVDs decreased to a greater extent over time when compared with the contained and p38i groups. Phosphorylated p38, tumor necrosis factor-α, and interleukin-1β were observed to exhibit higher expression levels in the non-contained group compared with the contained and p38i groups, at weeks 1 and 4 post-surgery. The expression level of caspase-3 and the densities of apoptotic disc cells were significantly higher in the non-contained group compared with the contained and p38i groups at 4 weeks post-surgery. In conclusion, p38 MAPK induces apoptosis in IVDs, while also accelerating the resorption of the relocated IVDs. Thus, p38 MAPK may be important in spontaneous resorption of IVDs.

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Intervertebral disc and macrophage interaction induces mechanical hyperalgesia and cytokine production in a herniated disc model in rats

Cited by 65 publications

References 50 publications

Inflammation in intervertebral disc degeneration and regeneration

Inflammation in intervertebral disc degeneration and regeneration

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

p38 mitogen-activated protein kinase inhibition modulates nucleus pulposus cell apoptosis in spontaneous resorption of herniated intervertebral discs: An experimental study in rats

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