Recovery of Intervertebral Disc Degeneration Post Enzymatic Treatment is Mediated by Matrix Metalloproteinases

2011 ◽  
Author(s):  
Nadeen Chahine ◽  
Nate Stetson ◽  
Neena Rajan ◽  
Daniel Grande ◽  
Mitchell Levine
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Enzymatic Degradation ◽  
Intervertebral Disc Degeneration ◽  
Biomechanical Properties ◽  
Enzymatic Treatment ◽  
Disc Injury ◽  
Herniated Discs ◽  
Dose Dependent

Enzymatic degradation of the intervertebral disc (IVD) with chondroitinase ABC (ChABC) reduces proteoglycan content of the IVD, thus simulating the GAG loss seen clinically in patients suffering from disc degeneration. This approach has been employed in models of disc injury in rats, rabbits and goats when administered over a large range of dosages [1–3]. Moreover, ChABC has also been used to induce repair of herniated discs in rabbits via chemonucleolysis [4, 5]. Despite the effectiveness of ChABC treatment to reduce the GAG content of the IVD, several recent studies including our own, have shown that this GAG loss is reversible at extended time points post enzymatic treatment [2,6,7]. The goal of the current study is to examine the dose dependent response of IVDs to degradation by ChABC in vivo. We hypothesize that administration of ChABC will result in dose dependent GAG loss and reduced mechanical properties. We administered ChABC at 0.1 U/ml, 1.0 U/ml and 10 U/ml and examined the changes in biomechanical properties, biochemical content, and gene expression in order to examine the biophysical and molecular mechanism by which GAG loss occurs in this model.

scholarly journals Quercetin Suppresses Apoptosis and Attenuates Intervertebral Disc Degeneration via the SIRT1-Autophagy Pathway

2020 ◽  
Vol 8 ◽  
Author(s):  
Dong Wang ◽  
Xin He ◽  
Di Wang ◽  
Pandi Peng ◽  
Xiaolong Xu ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Protective Effect ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Specific Effect ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Autophagy Pathway ◽  
Dose Dependent

Intervertebral disc degeneration (IDD) has been generally accepted as the major cause of low back pain (LBP), which causes an enormous socioeconomic burden. Previous studies demonstrated that the apoptosis of nucleus pulposus (NP) cells and the dyshomeostasis of extracellular matrix (ECM) contributed to the pathogenesis of IDD, and effective therapies were still lacking. Quercetin, a natural flavonoid possessing a specific effect of autophagy stimulation and SIRT1 activation, showed some protective effect on a series of degenerative diseases. Based on previous studies, we hypothesized that quercetin might have therapeutic effects on IDD by inhibiting the apoptosis of NP cells and dyshomeostasis of ECM via the SIRT1-autophagy pathway. In this study, we revealed that quercetin treatment inhibited the apoptosis of NP cells and ECM degeneration induced by oxidative stress. We also found that quercetin promoted the expression of SIRT1 and autophagy in NP cells in a dose-dependent manner. Autophagy inhibitor 3-methyladenine (3-MA) reversed the protective effect of quercetin on apoptosis and ECM degeneration. Moreover, SIRT1 enzymatic activity inhibitor EX-527, suppressed quercetin-induced autophagy and the protective effect on NP cells, indicating that quercetin protected NP cells against apoptosis and prevented ECM degeneration via SIRT1-autophagy pathway. In vivo, quercetin was also demonstrated to alleviate the progression of IDD in rats. Taken together, our results suggest that quercetin prevents IDD by promoting SIRT1-dependent autophagy, indicating one novel and effective therapeutic method for IDD.

scholarly journals An in vivo study of the effect of c-Jun on intervertebral disc degeneration in rats

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 4320-4330
Author(s):  
Ming Lei ◽  
Kangcheng Zhao ◽  
Wenbin Hua ◽  
Kun Wang ◽  
Shuai Li ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
In Vivo Study

scholarly journals Denosumab Alleviates Intervertebral Disc Degeneration Adjacent to a Lumbar Fusion by Inhibiting Endplate Osteochondral Remodeling and Vertebral Osteoporosis in Ovariectomized Rats

2020 ◽  
Author(s):  
Qi Sun ◽  
Fa-Ming Tian ◽  
Fang Liu ◽  
Jia-Kang Fang ◽  
Yun-Peng Hu ◽  
...  
Keyword(s):  
Bone Formation ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Lumbar Fusion ◽  
Biomechanical Properties ◽  
Disc Height ◽  
X Ray ◽  
Manual Palpation ◽  
Trap Staining

Abstract Background: Although adjacent segmental intervertebral disc degeneration (ASDD) is one of the most common complications after lumbar fusion, its exact mechanism remains unclear. As an antibody to RANKL, denosumab (Dmab) effectively reduces bone resorption and stimulates bone formation, which can increase bone mineral density (BMD) and improve osteoporosis. However, it has not been confirmed whether Dmab has a reversing or retarding effect on ASDD. Methods: Three-month-old female Sprague-Dawley rats that underwent L4–L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation four weeks after OVX surgery were given Dmab four weeks after PLF surgery (OVX+PLF+Dmab group). In addition, the following control groups were defined: Sham, OVX, PLF, and OVX+PLF (n=12 each).Then, manual palpation and X-ray were used to evaluate the state of lumbar fusion. The bone microstructure in the lumbar vertebra and endplate as well as the disc height index (DHI) of the L5/6 were evaluated by microcomputed tomography (μCT). The characteristic alterations of ASDD were identified via Safranin-O green staining staining. Osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining and the biomechanical properties of vertebra were evaluated. Aggrecan (Agg), metalloproteinase-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) expression in the intervertebral disc were detected by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) analysis.Results: Manual palpation showed clear evidence of the fused segment’s immobility. Compared to the OVX+PLF group, more new bone formation was observed by X-ray examination in the OVX+PLF+Dmab group. Dmab significantly alleviated ASDD by retaining disc height index (DHI), decreasing porosity of endplate, and increasing the biomechanical properties and BMD of vertebra. TRAP staining results showed a significantly decreased number after Dmab treatment, especially in subchondral bone and cartilaginous endplate. Moreover, the results of protein and mRNA expression in intervertebral disc (IVD) showed that Dmab not only inhibited matrix degradation by decreasing MMP-13 and ADAMTS-4 but also promoted matrix synthesis by increasing Agg. Conclusions: These results suggest that Dmab may be a novel therapeutic target for the treatment of ASDD.

scholarly journals Antiaging Factor Klotho Retards the Progress of Intervertebral Disc Degeneration through the Toll-Like Receptor 4-NF-κB Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fangfang Bi ◽  
Wenbo Liu ◽  
Zongtao Wu ◽  
Chen Ji ◽  
Cuicui Chang
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Acute Inflammation ◽  
Protective Effects ◽  
Toll Like Receptor ◽  
Inhibitory Effects ◽  
Toll Like Receptor 4 ◽  
Disc Injury ◽  
Anti Inflammation

Antiaging protein Klotho exhibits impressive properties of anti-inflammation, however is declined early after intervertebral disc injury, making Klotho restoration an attractive strategy of treating intervertebral disc inflammatory disorders. Here, we have found that Klotho is enriched in nucleus pulposus (NP) cells and Klotho overexpression attenuates H2O2-induced acute inflammation essentially via suppressing Toll-like receptor 4 (TLR4). The proinflammatory NF-κB signaling and cytokine expressions paralleled with Klotho repression and TLR4 elevation in both NP cells (H2O2 treatment) and rat intervertebral disc (needle puncture treatment). Overexpression of TLR4 downregulated expression of Klotho, whereas interfering TLR4 expression diminished the inhibitory effects of H2O2 on Klotho in NP cells. Consistently, Klotho knockdown by RNA interferences largely diminished the anti-inflammatory and intervertebral disc protective effects in an Intervertebral Disc Degeneration (IDD) model. Thus, our study indicates that TLR4-NF-κB signaling and Klotho form a negative-feedback loop in NP cells. Also, we demonstrate that the expression of Klotho is regulated by the balance between upregulation and downregulation of TLR4-NF-κB signaling.

scholarly journals A novel in vivo mouse intervertebral disc degeneration model induced by compressive suture

2021 ◽  
Vol 398 (1) ◽  
pp. 112359
Author(s):  
Zhuochao Liu ◽  
Qi Zhou ◽  
Jiancheng Zheng ◽  
Changwei Li ◽  
Weibin Zhang ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration

scholarly journals Dietary polyphenols as a safe and novel intervention for modulating pain associated with intervertebral disc degeneration in an in-vivo rat model

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0223435 ◽  
Author(s):  
Alon Lai ◽  
Lap Ho ◽  
Thomas W. Evashwick-Rogler ◽  
Hironobu Watanabe ◽  
Jonathan Salandra ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Rat Model ◽  
Intervertebral Disc Degeneration ◽  
Dietary Polyphenols

8:42 An in vivo study of Sox9 gene therapy for intervertebral disc degeneration

2002 ◽  
Vol 2 (5) ◽  
pp. 50 ◽  
Author(s):  
Nikola Nenadovich ◽  
Frank Phillips ◽  
T.C. He ◽  
Rex Haydon ◽  
Hongwei Cheng
Keyword(s):  
Gene Therapy ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
In Vivo Study ◽  
Sox9 Gene
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