TNF-Alpha in Nucleus Pulposus Induces Sensory Nerve Growth

Hayashi, Shinu; Taira, Akiko; Inoue, Gen; Koshi, Takana; Ito, Toshinori; Yamashita, Masaomi; Yamauchi, Kazuyo; Suzuki, Mitsuaki; Takahashi, Kazuhisa; Ohtori, Seiji

doi:10.1097/brs.0b013e318178e5ea

Cited by 56 publications

(12 citation statements)

References 25 publications

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“…There is accumulating evidence that IL-1β is capable of upregulating zinc-based matrix degrading enzymes, in particular matrix metalloproteinases, disintegrins, and metalloproteinases with thrombospondin motif, which may lead to degradation of collagen II and proteoglycan, as a result of losing ECM and severely reducing the ability of the NP to retain water 26 . TNF-α has been implicated in disc herniation and nerve root pain 27 . Teixeira et al showed a new therapeutic method for IVD degeneration by diclofenac-nanoparticles intradiscal injection, based on the modulation of inflammation 28 .…”

Section: Discussionmentioning

confidence: 99%

Prolactin inhibits the progression of intervertebral disc degeneration through inactivation of the NF-κB pathway in rats

Liu

Guo

et al. 2018

Cell Death Dis

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Intervertebral disc degeneration (IVDD) is one of the key predisposing factors for low back pain. Although the exact mechanism remains unclear, inflammatory response and nucleus pulposus (NP) apoptosis are known to play important roles in this process. Prolactin protects against inflammation-associated chondrocyte apoptosis in arthritis. Based on prior studies, we hypothesized that prolactin might have therapeutic effects on IVDD by inhibiting the apoptosis of degenerative human disc NP cells. An experimental model of IVDD was established in 3-month-old Sprague-Dawley rats by submitting them to percutaneous disc puncture with a 20-gauge needle on levels 7–8 and 8–9 of the coccygeal vertebrae. Then the rats were injected with 20 or 200 ng prolactin on a weekly basis. Radiologic and histologic analyses were performed on days 4, 7, 14, and 28. The expression of prolactin and its receptor was analyzed in human tissue obtained from symptomatic patients undergoing microencoscopy discectomy, or from scoliosis patients undergoing deformity correction surgery. The results showed that intradiscal injection of prolactin maintained disc height and the mean signal intensity of the punctured disc. Histological analysis indicated that prolactin treatment significantly retained the complete structure of the NP and annulus fibrosus compared with the vehicle group. In addition, more collagen II, but fewer collagen I-containing tissues were detected in the prolactin treatment groups compared to the vehicle group. Moreover, low levels of tumor necrosis factor-α, interleukin-1β, cleaved-caspase 3, and TUNEL staining were observed in the prolactin treatment groups. We also demonstrated that prolactin impaired puncture-induced inflammation and cell apoptosis by downregulating activation of the NF-κB pathway. The degenerated NP tissues from patients had decreased expression of prolactin and its receptor, whereas expression was increased in the NP tissues removed from scoliosis patients. These results suggest that prolactin may be a novel therapeutic target for the treatment of IVDD.

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Section: Discussionmentioning

confidence: 99%

Prolactin inhibits the progression of intervertebral disc degeneration through inactivation of the NF-κB pathway in rats

Liu

Guo

et al. 2018

Cell Death Dis

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“…Homeostatic TNFSF/TNFRSF expression in the brain of mammals appears to be important for multiple neurological functions, including promoting nerve growth (Hayashi et al, 2008; Mi, 2008), differentiation (Hou et al, 2008), innervations (O’Keeffe et al, 2008), sensitization (Czeschik et al, 2008), and dendrite formation (Shao et al, 2005), and is supported by several streams of evidence. Firstly, TNFSF/TNFRSF expression occurs in the normal brain of the fetus, neonate, adolescent and adult mammal in developmentally regulated patterns and does not appear to induce neurological disease or inflammation (Twohig et al, 2010).…”

Section: The Neurological Expression Of the Tnfsf/tnfrsf Proteins Is mentioning

confidence: 96%

The role of tumor necrosis factor receptor superfamily members in mammalian brain development, function and homeostasis

Twohig

Cuff

Yong

et al. 2011

Reviews in the Neurosciences

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Tumor necrosis factor receptor superfamily (TNFRSF) members were initially identified as immunological mediators, and are still commonly perceived as immunological molecules. However, our understanding of the diversity of TNFRSF members' roles in mammalian physiology has grown significantly since the first discovery of TNFRp55 (TNFRSF1) in 1975. In particular, the last decade has provided evidence for important roles in brain development, function and the emergent field of neuronal homeostasis. Recent evidence suggests that TNFRSF members are expressed in an overlapping regulated pattern during neuronal development, participating in the regulation of neuronal expansion, growth, differentiation and regional pattern development. This review examines evidence for non-immunological roles of TNFRSF members in brain development, function and maintenance under normal physiological conditions. In addition, several aspects of brain function during inflammation will also be described, when illuminating and relevant to the non-immunological role of TNFRSF members. Finally, key questions in the field will be outlined.

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“…Secreted proinflammatory mediators include TNF-α, IL-1 α/β, IL-6, IL-17, IL-8, IL-2, IL-4, IL-10, IFN-γ, chemokines, prostaglandin (PGE)2, of these TNF-α and IL-1β are probably the most studied 20–24 . TNF-α has been implicated in disc herniation and nerve irritation and ingrowth 25,26 , while both TNF-α and IL-1β induce upregulation of genes encoding matrix-degrading enzymes 20,27,28 . It has been demonstrated that expression of IL-1β and IL-1R are increased in degenerated disc tissue 20,21 .…”

Section: Introductionmentioning

confidence: 99%

Role of cytokines in intervertebral disc degeneration: pain and disc content

2013

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Degeneration of the intervertebral disc is the major contributor to back/neck and radicular pain. It is characterized by an elevation in levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1 α/β, IL-6 and IL-17 secreted by the disc cells themselves; these cytokines promote matrix degradation, chemokine production and changes in cell phenotype. The resulting imbalance between catabolic and anabolic responses leads to degeneration, as well as herniation and radicular pain. Release of chemokines from degenerating discs promote infiltration and activation of T and B cells, macrophages, neutrophils, and mast cells further amplifying the inflammatory cascade. Immunocyte migration into the disc is accompanied by the appearance of microvasculature and nerve fibers arising from the dorsal root ganglion (DRG). In this inflammatory milieu, neurogenic factors in particular nerve growth factor (NGF) and brain-derive neurotrophic factor (BDNF) generated by disc and immune cells induce expression of pain associated cation channels in DRGs. Depolarization of these channels is likely to promote discogenic and radicular pain and reinforce the cytokine-mediated degenerative cascade. Taken together, the enhanced understanding of the contribution of cytokines and immune cells to catabolic and nociceptive processes provide new targets for treating symptomatic disc disease.

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TNF-Alpha in Nucleus Pulposus Induces Sensory Nerve Growth

Cited by 56 publications

References 25 publications

Prolactin inhibits the progression of intervertebral disc degeneration through inactivation of the NF-κB pathway in rats

Prolactin inhibits the progression of intervertebral disc degeneration through inactivation of the NF-κB pathway in rats

The role of tumor necrosis factor receptor superfamily members in mammalian brain development, function and homeostasis

Role of cytokines in intervertebral disc degeneration: pain and disc content

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