Dominance of chemokine ligand 2 and matrix metalloproteinase-2 and -9 and suppression of pro-inflammatory cytokines in the epidural compartment after intervertebral disc extrusion in a canine model

Karli, Philemon; Martlé, Valentine; Bossens, Kenny; Summerfield, Artur; Doherr, Marcus G.; Turner, Paul J.; Vandevelde, M.; Forterre, Franck; Henke, Diana

doi:10.1016/j.spinee.2014.05.021

Cited by 29 publications

(47 citation statements)

References 53 publications

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“…Extruded disk material initiates an inflammatory cascade within the vertebral canal, leading to upregulation of inflammatory markers, proliferation of soft tissues, and disturbances of CSF flow and vascular drainage of nerve roots and dorsal root ganglia, which can result in intraradicular edema formation. [31][32][33] Compressed nerves further thicken owing to progressive fibrotic hypertrophy with Renaut body formation. 33,e These changes can initiate a self-perpetuating cascade, causing progressive spinal nerve compression and ultimately resulting in chronic hyperesthesia poorly responsive to conventional analgesics.…”

Section: Discussionmentioning

confidence: 99%

Clinical characterization of thoracolumbar and lumbar intervertebral disk extrusions in English Cocker Spaniels

Cardy¹,

Tzounos²,

Volk³

et al. 2016

javma

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OBJECTIVE To assess the anatomic distribution of thoracolumbar and lumbar intervertebral disk extrusions (IVDEs) in English Cocker Spaniels as compared with findings in Dachshunds and to characterize clinical findings in English Cocker Spaniels with thoracolumbar or lumbar IVDEs affecting various regions of the vertebral column. DESIGN Retrospective observational study. ANIMALS 81 English Cocker Spaniels and 81 Dachshunds with IVDEs. PROCEDURES Signalment, clinical signs, neurologic examination findings, and affected intervertebral disk spaces (IVDSs) were recorded for both breeds. Management methods and outcomes were recorded for English Cocker Spaniels. Lesions were categorized as thoracolumbar (IVDSs T9–10 through L1–2), midlumbar (L2–3 through L4–5), or caudal lumbar (L5–6 through L7–S1). RESULTS Midlumbar and caudal lumbar IVDEs were significantly more common in English Cocker Spaniels than in Dachshunds. English Cocker Spaniels with caudal lumbar IVDEs had a longer median duration of clinical signs before evaluation and more commonly had unilateral pelvic limb lameness or spinal hyperesthesia as the predominant clinical sign than did those with IVDEs at other sites. Those with caudal lumbar IVDEs less commonly had neurologic deficits and had a higher median neurologic grade (indicating lesser severity), shorter mean postoperative hospitalization time, and faster mean time to ambulation after surgery than those with other sites affected. These variables did not differ between English Cocker Spaniels with thoracolumbar and midlumbar IVDEs. CONCLUSIONS AND CLINICAL RELEVANCE Caudal and midlumbar IVDEs were more common in English Cocker Spaniels than in Dachshunds. English Cocker Spaniels with caudal lumbar IVDE had clinical signs and posttreatment responses that differed from those in dogs with midlumbar or thoracolumbar IVDE.

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Section: Discussionmentioning

confidence: 99%

Clinical characterization of thoracolumbar and lumbar intervertebral disk extrusions in English Cocker Spaniels

Cardy¹,

Tzounos²,

Volk³

et al. 2016

javma

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show abstract

“…In addition, in the degenerative intervertebral disc, cell proliferation and function was confined by low oxygen tension, poor nutrition supply, and even degradation and inflammatory factors. [22][23][24] In the study of Liang et al, 25 the effectiveness of adenovirus-mediated growth and differentiation factor-5 (Ad-GDF5) had been demonstrated in reverse disc degeneration in mice disc degeneration model. These results might be related to the function of GDF5 in promoting cell proliferation and ECM secretion (type II collagen and aggrecan protein), and suppressing the expression of matrix metalloproteinase-3 (MMP-3), which was a vital degradation factor in disc degeneration process.…”

Section: Discussionmentioning

confidence: 99%

Intervention of rAAV-hTERT-Transducted Nucleus Pulposus Cells in Early Stage of Intervertebral Disc Degeneration: A Study in Canine Model

Shi

Xin

et al. 2015

Tissue Engineering Part A

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“…A previous study demonstrated that IL-2 mRNA expression was downregulated in the epidural compartment following intervertebral disc extrusion (9), and IL-2 expression levels in the disc samples of patients with lumbar degenerative disc disease were significantly increased, as compared with the controls (10). These findings suggested that IL-2 may be associated with intervertebral disc disease; however, the role of IL-2 in the cellular functions of intervertebral disc tissues remains unclear.…”

Section: Introductionmentioning

confidence: 94%

Interleukin-2 is upregulated in patients with a prolapsed lumbar intervertebral disc and modulates cell proliferation, apoptosis and extracellular matrix metabolism of human nucleus pulposus cells

Wang

Zhu

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Previous studies have demonstrated that the expression levels of cytokines are increased in degenerated intervertebral disc tissues, and several cytokines are associated with the pathogenesis of intervertebral disc degeneration. However, the role of interleukin (IL)-2 in the cellular functions of intervertebral disc tissues remains unreported. The present study aimed to determine the expression levels of IL-2 in the nucleus pulposus (NP) tissues of patients with a prolapsed lumbar intervertebral disc; and to observe the changes in cell proliferation, apoptosis, extracellular matrix (ECM) metabolism and p38 mitogen-activated protein kinase (MAPK) signaling in human NP cells (HNPCs) following treatment with IL-2. The present study demonstrated that IL-2 expression levels were upregulated in the NP tissues of patients with a prolapsed lumbar intervertebral disc; and a subsequent MTT assay demonstrated that IL-2 inhibits the proliferation of HNPCs in a dose-dependent manner. Furthermore, as demonstrated by the increased protein expression levels of Fas cell surface death receptor and the induction of caspase-8 and caspase-3 activity, the death receptor pathway was activated by IL-2 in the HNPCs in order to promote cell apoptosis. In addition, IL-2 promoted ECM degradation in the HNPCs, as demonstrated by an increase in the expression levels of type I collagen, a disintegrin and metalloproteinase with thrombospondin motifs and matrix metalloproteinases, and decreased aggrecan and type II collagen expression levels. Furthermore, phosphorylated-p38 was significantly increased in the HNPCs following IL-2 treatment. In conclusion, the present study demonstrated that IL-2 inhibits cell proliferation, and induces cell apoptosis and ECM degradation, accompanied by the activation of p38 MAPK signaling in HNPCs. Therefore, IL-2 may be a potential therapeutic agent for the treatment of degenerative disc disease. IntroductionThe prolapse of a lumbar intervertebral disc is a common ailment that places pressure on the surrounding nerves and causes pain in the waist and leg. Intervertebral disc degeneration (IDD) has been demonstrated to be the main cause of lumbar intervertebral disc prolapse. Approximately 20% of teenage indiciduals have discs with mild signs of degeneration, while ~10% of 50-year-old individuals and ~60% of 70-year-old individuals posses discs that exhibit severe degeneration (1). However, the pathogenesis of IDD is associated with various cellular and biochemical alterations (2). IDD is associated with numerous risk factors, including lifestyle, co-morbidities, genetic predisposition and age (3).Previous studies have detected high expression levels of cytokines in degenerated intervertebral disc tissues, including interleukin (IL)-1, interferon (IFN)-γ and tumor necrosis factor (TNF)-α, and these cytokines are associated with the pathogenesis of IDD (4-6).IL-2, which is a pleiotropic cytokine primarily produced by T lymphocytes, has been implicated in the development and control of inflammatory disea...

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Dominance of chemokine ligand 2 and matrix metalloproteinase-2 and -9 and suppression of pro-inflammatory cytokines in the epidural compartment after intervertebral disc extrusion in a canine model

Cited by 29 publications

References 53 publications

Clinical characterization of thoracolumbar and lumbar intervertebral disk extrusions in English Cocker Spaniels

Clinical characterization of thoracolumbar and lumbar intervertebral disk extrusions in English Cocker Spaniels

Intervention of rAAV-hTERT-Transducted Nucleus Pulposus Cells in Early Stage of Intervertebral Disc Degeneration: A Study in Canine Model

Interleukin-2 is upregulated in patients with a prolapsed lumbar intervertebral disc and modulates cell proliferation, apoptosis and extracellular matrix metabolism of human nucleus pulposus cells

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