Molecular Basis of Intervertebral Disc Degeneration

Gopal, Dipika; Ho, Allen L.; Shah, Amol; John, H.

doi:10.1007/978-1-4614-4090-1_8

Cited by 49 publications

(32 citation statements)

References 105 publications

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“…Glycosaminoglycan is an important type of proteoglycan that maintains the osmotic gradient . Therefore, the GAG content was analyzed by DMMB assay, normalized with DNA content .…”

Section: Discussionmentioning

confidence: 99%

Functional self‐assembled peptide scaffold inhibits tumor necrosis factor‐alpha‐induced inflammation and apoptosis in nucleus pulposus cells by suppressing nuclear factor‐κB signaling

Cheng

et al. 2017

J Biomedical Materials Res

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Although nucleus pulposus (NP) tissue engineering has achieved tremendous success, researches still face the huge obstacles in maintaining cell survival and function. A novel functional self-assembled peptide RADA-KPSS was constructed by conjugating BMP-7 short active fragment (KPSS) to the C-terminus of RADA16-I that displays anti-inflammatory and anti-apoptosis effects. However, whether this functional self-assembled RADA-KPSS peptide can alleviate inflammation and NPC apoptosis induced by tumor necrosis factor-alpha (TNF-α) has not been studied. Therefore, we cultured NPCs treated with TNF-α for 48 h with the RADA-KPSS peptide, and compared the results to those with RADA16-I peptide. The cell apoptosis rate, inflammatory mediator secretion, expression of matrix-degrading enzymes, and extracellular matrix (ECM) protein levels were evaluated. The expression of nuclear factor-κB-p65 (NF-κB-p65) protein was also tested. TNF-α-treated NPCs cultured with the RADA16-I peptide showed up-regulated gene expression for matrix-degrading enzymes, such as matrix metalloproteinases-3 (MMP-3), MMP-9, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4), and down-regulated gene expression for ECM proteins such as aggrecan, collagen II, and Sox-9. The RADA-KPSS peptide could attenuate the expression of MMP-3, MMP-9, and ADAMTS-4, promote accumulation of ECM proteins, and increase secretion of glycosaminoglycan as compared with the RADA16-I peptide. Moreover, the TNF-α-damaged NPCs was further demonstrated to inhibit NF-κB-p65, IL-1, IL-6, and prostaglandin E-2 proteins and decrease cell apoptosis in RADA-KPSS peptide. In conclusion, the functional self-assembled RADA-KPSS peptides have anti-inflammatory and anti-apoptotic effects by promoting anabolic processes and inhibiting catabolic processes in intervertebral disk degeneration. These peptides may be feasible for clinical applications in NP tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1082-1091, 2018.

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“…Glycosaminoglycan is an important type of proteoglycan that maintains the osmotic gradient . Therefore, the GAG content was analyzed by DMMB assay, normalized with DNA content .…”

Section: Discussionmentioning

confidence: 99%

Functional self‐assembled peptide scaffold inhibits tumor necrosis factor‐alpha‐induced inflammation and apoptosis in nucleus pulposus cells by suppressing nuclear factor‐κB signaling

Cheng

et al. 2017

J Biomedical Materials Res

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“…This is also a global problem, as demonstrated by the World Health Organization’s declaration that back pain is an epidemic, affecting 80% of the population at some point in their lives [3]. Although the majority of back and neck issues can be treated conservatively, a significant proportion of patients go on to develop progressive issues including instability, deformity, neurologic deficit, and intractable pain [4,5]. The treatment in severe cases is arthrodesis (or fusion), where vertebrae are fixed together by an endoprosthetic, and an osteoconductive material is positioned between the vertebrae in an attempt to prompt bone growth.…”

Section: Introductionmentioning

confidence: 99%

An allograft generated from adult stem cells and their secreted products efficiently fuses vertebrae in immunocompromised athymic rats and inhibits local immune responses

et al. 2017

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BACKGROUND CONTEXT Spine pain and the disability associated with it are epidemic in the United States. According to the National Center for Health Statistics, more than 650,000 spinal fusion surgeries are performed annually in the United States, and yet there is a failure rate of 15%–40% when standard methods employing current commercial bone substitutes are used. Autologous bone graft is the gold standard in terms of fusion success, but the morbidity associated with the procedure and the limitations in the availability of sufficient material have limited its use in the majority of cases. A freely available and immunologically compatible bone mimetic with the properties of live tissue is likely to substantially improve the outcome of spine fusion procedures without the disadvantages of autologous bone graft. PURPOSE This study aimed to compare a live human bone tissue analog with autologous bone grafting in an immunocompromised rat model of posterolateral fusion. DESIGN/SETTING This is an in vitro and in vivo preclinical study of a novel human stem cell–derived construct for efficacy in posterolateral lumbar spine fusion. METHODS Osteogenically enhanced human mesenchymal stem cells (OEhMSCs) were generated by exposure to conditions that activate the early stages of osteogenesis. Immunologic characteristics of OEhMSCs were evaluated in vitro. The secreted extracellular matrix from OEhMSCs was deposited on a clinical-grade gelatin sponge, resulting in bioconditioned gelatin sponge (BGS). Bioconditioned gelatin sponge was used alone, with live OEhMSCs (BGS+OEhMSCs), or with whole human bone marrow (BGS+hBM). Efficacy for spine fusion was determined by an institutionally approved animal model using 53 nude rats. RESULTS Bioconditioned gelatin sponge with live OEhMSCs did not cause cytotoxicity when incubated with immunologically mismatched lymphocytes, and OEhMSCs inhibited lymphocyte expansion in mixed lymphocyte assays. Bioconditioned gelatin sponge with live OEhMSC and BGS+hBM constructs induced profound bone growth at fusion sites in vivo, with a comparable rate of fusion with syngeneic bone graft (negative [0 of 10], BGS alone [0 of 10], bone graft [7 of 10], BGS+OEhMSC [10 of 15], and BGS+hBM [8 of 8]). CONCLUSIONS Collectively, these studies demonstrate that BGS+OEhMSC constructs possess low immunogenicity and drive vertebral fusion with efficiency matching syngeneic bone graft in rodents. We also demonstrate that BGS serves as a promising scaffold for spine fusion when combined with hBM.

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“…[3] In addition, there is a growing body of researches to suggest that the pathology mechanism and autoimmunity mechanism of LDH play a vital role in explaining the disc herniation-derived low back pain and leg radicular pain, but their exact effects and the mechanisms involved remain obscure. [4,5] Available efficacy data supported that the use of analgesics, nonsteroidal anti-inflammatory drugs and epidural steroid injections probably could relieve the associated pain and improve the quality of life without radically changing the midterm outcome. [6] In our study, based on researches of mechanisms of LDH and injection therapy, we speculate that local irrigation of herniated lumber disc area may have a positive effect.…”

Section: Introductionmentioning

confidence: 99%

Does local lavage influence functional recovery during lumber discectomy of disc herniation?

Zhu

Ren²,

Yuan³

et al. 2016

Medicine

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Lumbar disc herniation (LDH) is a common disease and lumbar discectomy is the most common surgical procedure carried out for patients with low back pain and leg symptoms. Although most researchers are focusing on the surgical techniques during operation, the aim of this study is to evaluate the effect of local intervertebral lavage during microdiscectomy.In this retrospective study, 410 patients were operated on by microdiscectomy for LDH during 2011 to 2014. Retrospectively, 213 of them (group A) accepted local intervertebral irrigation with saline water before wound closure and 197 patients (group B) only had their operative field irrigated with saline water. Systematic records of visual analog scores (VAS), Oswestry disability Index (ODI) questionnaire scale scores, use of analgesia, and hospital length of stay were done after hospitalization.The majority (80.49%) of the cases were diagnosed with lumber herniation at the levels of L4/5 and L5/S1. Fifty-one patients had herniations at 2 levels. There were significant decreases of VAS scores and ODI in both groups between preoperation and postoperation of different time points. VAS scores decreased more in group A than group B at early stage of postoperation follow-up. However, there were no statistically significant differences between 2 groups in using analgesia, VAS and ODI up to 1 month of follow-up.Microdiscectomy for LDH offers a marked improvement in back and radicular pain. Local irrigation of herniated lumber disc area could relief dick herniation-derived low back pain and leg radicular pain at early stage of post-operation. However, the pain relief of this intervention was not noticeable for a long period.

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Molecular Basis of Intervertebral Disc Degeneration

Cited by 49 publications

References 105 publications

Functional self‐assembled peptide scaffold inhibits tumor necrosis factor‐alpha‐induced inflammation and apoptosis in nucleus pulposus cells by suppressing nuclear factor‐κB signaling

Functional self‐assembled peptide scaffold inhibits tumor necrosis factor‐alpha‐induced inflammation and apoptosis in nucleus pulposus cells by suppressing nuclear factor‐κB signaling

An allograft generated from adult stem cells and their secreted products efficiently fuses vertebrae in immunocompromised athymic rats and inhibits local immune responses

Does local lavage influence functional recovery during lumber discectomy of disc herniation?

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