Inflammatory profiles in canine intervertebral disc degeneration

Abstract

BackgroundIntervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE2), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs.ResultsPGE2 levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples.ConclusionsPGE2 levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the AF increased with advancing degeneration stages. Although macrophages invaded the AF as degeneration progressed, the production of inflammatory mediators seemed most pronounced in degenerated NP tissue. Future studies are needed to investigate if inhibition of PGE2 levels in degenerated IVDs provides effective analgesia and exerts a protective role in the process of IVD degeneration and the development of IVD disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0635-6) contains supplementary material, which is available to authorized users.

Experimental Application of Bone Marrow Mesenchymal Stem Cells for the Repair of Intervertebral Disc Annulus Fibrosus

“…The results indicated that transplantation of BMSCs was effective in repairing intervertebral disc annulus fibrosus, which is consistent with the findings of Chen et al [9]. As shown in Table 2, although the level of type II collagen was decreased after surgery in both groups, it was significantly higher in the observation group than in the control group at 2, 4, 8, and 12 weeks after surgery, which is consistent with the findings of Yi et al [10]. In the control group, the level of type II collagen slightly increased at 4 weeks compared to 2 weeks when the treatment began, but then gradually decreased.…”

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine

“…Therefore, evidence linking wear debris-induced activation of immune cells to pain sensitization would establish a mechanism unique to the physiology of the lumbar spine. It is well accepted from studies on painful DDD that the pathology involves the proliferation of fibroblasts and infiltration of macrophages into the annulus fibrosus in conjunction with the production of pain-associated proteins [4,8,43]. Specifically, activated macrophages have been reported to contribute to experimental pain states by releasing factors such as TNFa, IL-1b, IL-8, NGF, nitric oxide, and prostanoids [22,33,37].…”

17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway

“…TNF-α is one type of inflammatory cytokines which is secreted by monocytes and macrophages, and plays an important role in inflammatory response, cells proliferation, and apoptosis [36,37]. TNF-α is also a critical inflammatory cytokines causing IVDD [38,39]. Andrade et al [38] found that when compared with first time lumbar disc herniation (LDH) patients, recurrent LDH patients had higher levels of TNF-α, and they discovered that TNF-α and its receptors (TNFR) were correlated with the severity of pre- and post-operative leg pain in LDH patients; conclusions which our study supports.…”