Degenerative Intervertebral Disc Disease Research Articles

Protective Effects of Growth Differentiation Factor-6 on the Intervertebral Disc: An In Vitro and In Vivo Study.

Growth differentiation factors (GDFs) regulate homeostasis by amplifying extracellular matrix anabolism and inhibiting pro-inflammatory cytokine production in the intervertebral disc (IVD). The aim of this study was to elucidate the effects of GDF-6 on human IVD nucleus pulposus (NP) cells using a three-dimensional culturing system in vitro and on rat tail IVD tissues using a puncture model in vivo. In vitro, Western blotting showed decreased GDF-6 expression with age and degeneration severity in surgically collected human IVD tissues (n = 12). Then, in moderately degenerated human IVD NP cells treated with GDF-6 (100 ng/mL), immunofluorescence demonstrated an increased expression of matrix components including aggrecan and type II collagen. Quantitative polymerase chain reaction analysis also presented GDF-6-induced downregulation of pro-inflammatory tumor necrosis factor (TNF)-α (p = 0.014) and interleukin (IL)-6 (p = 0.016) gene expression stimulated by IL-1β (10 ng/mL). Furthermore, in the mitogen-activated protein kinase pathway, Western blotting displayed GDF-6-induced suppression of p38 phosphorylation (p = 0.041) under IL-1β stimulation. In vivo, intradiscal co-administration of GDF-6 and atelocollagen was effective in alleviating rat tail IVD annular puncture-induced radiologic height loss (p = 0.005), histomorphological degeneration (p < 0.001), matrix metabolism (aggrecan, p < 0.001; type II collagen, p = 0.001), and pro-inflammatory cytokine production (TNF-α, p < 0.001; IL-6, p < 0.001). Consequently, GDF-6 could be a therapeutic growth factor for degenerative IVD disease.

Reparative effects of chronic intermittent hypobaric hypoxia pre‑treatment on intervertebral disc degeneration in rats.

Previous studies have indicated that chronic intermittent hypobaric hypoxia (CIHH) preconditioning can inhibit TNF-α and other related inflammatory cytokines and exerts protective effect on intervertebral disc degeneration disease (IDD) in rats; however, the mechanism is still unclear. The present study aimed to explore the repair mechanisms of CIHH on IDD in rats. In the experiment, 48 adult Sprague-Dawley rats were selected and randomly divided into an experimental group (CIHH-IDD), a degenerative group (IDD) and a control group (CON). The CIHH-IDD group of rats (n=16) were treated with CIHH (simulated 3000 m altitude, 5 h per day, 28 days; PO2=108.8 mmHg) before disc degeneration surgery. The IDD group of rats (n=16) underwent tail-vertebral intervertebral disc surgery to establish a model of intervertebral disc degeneration. The CON group of rats (n=16) did not receive any treatments. After surgery, the disc height index was calculated using X-ray analysis of rat tail vertebrae, the degeneration process was observed and repair was evaluated by chemically staining degenerative intervertebral disc tissue slices. The expression levels of basic fibroblast growth factor (bFGF), TGFβ1, Collagen I and Collagen II were measured in the intervertebral disc tissue using western blotting; while the expression levels of bFGF, TGFβ1 and hypoxia-inducible factor 1-α (HIF-1α) were measured in rat serum using ELISA. The results demonstrated that: i) The degree of intervertebral disc height degeneration in CIHH-IDD rats was significantly lower compared with that in IDD rats (P<0.05); ii) the expression levels of bFGF, TGFβ1 and HIF-1α were higher in CIHH-IDD rat serum compared with those in IDD rat serum (P<0.05); iii) optical microscopy revealed that the degree of disc degeneration was relatively mild in CIHH-IDD rats; and iv) the protein expression levels of bFGF, TGFβ1 and collagen II were increased in CIHH-IDD rat intervertebral disc tissues compared with those of IDD rats, while the overexpression of collagen I protein was inhibited. Overall, after CIHH pre-treatment, the expression levels of bFGF and TGFβ1 were up-regulated, which play notable roles in repairing degenerative intervertebral discs in rats.

Biomaterials and Cell-Based Regenerative Therapies for Intervertebral Disc Degeneration with a Focus on Biological and Biomechanical Functional Repair: Targeting Treatments for Disc Herniation.

Intervertebral disc (IVD) degeneration is a common cause of low back pain and most spinal disorders. As IVD degeneration is a major obstacle to the healthy life of so many individuals, it is a major issue that needs to be overcome. Currently, there is no clinical treatment for the regeneration of degenerated IVDs. However, recent advances in regenerative medicine and tissue engineering suggest the potential of cell-based and/or biomaterial-based IVD regeneration therapies. These treatments may be indicated for patients with IVDs in the intermediate degenerative stage, a point where the number of viable cells decreases, and the structural integrity of the disc begins to collapse. However, there are many biological, biomechanical, and clinical challenges that must be overcome before the clinical application of these IVD regeneration therapies can be realized. This review summarizes the basic research and clinical trials literature on cell-based and biomaterial-based IVD regenerative therapies and outlines the important role of these strategies in regenerative treatment for IVD degenerative diseases, especially disc herniation.

Intervertebral Disc-on-a-Chip as Advanced In Vitro Model for Mechanobiology Research and Drug Testing: A Review and Perspective.

Discogenic back pain is one of the most diffused musculoskeletal pathologies and a hurdle to a good quality of life for millions of people. Existing therapeutic options are exclusively directed at reducing symptoms, not at targeting the underlying, still poorly understood, degenerative processes. Common intervertebral disc (IVD) disease models still do not fully replicate the course of degenerative IVD disease. Advanced disease models that incorporate mechanical loading are needed to investigate pathological causes and processes, as well as to identify therapeutic targets. Organs-on-chip (OoC) are microfluidic-based devices that aim at recapitulating tissue functions in vitro by introducing key features of the tissue microenvironment (e.g., 3D architecture, soluble signals and mechanical conditioning). In this review we analyze and depict existing OoC platforms used to investigate pathological alterations of IVD cells/tissues and discuss their benefits and limitations. Starting from the consideration that mechanobiology plays a pivotal role in both IVD homeostasis and degeneration, we then focus on OoC settings enabling to recapitulate physiological or aberrant mechanical loading, in conjunction with other relevant features (such as inflammation). Finally, we propose our view on design criteria for IVD-on-a-chip systems, offering a future perspective to model IVD mechanobiology.

Comparison between T2-weighted two-dimensional and three-dimensional fast spin-echo MRI sequences for characterizing thoracolumbar intervertebral disc disease in small-breed dogs.

Magnetic resonance imaging (MRI) is a standard test for diagnosis and treatment planning in dogs with degenerative thoracolumbar intervertebral disc disease (IVDD). However, published studies evaluating three-dimensional fast-spin echo (3D-FSE) pulse sequences for dogs with IVDD are currently limited. Aims of this retrospective, observational study were to compare findings from T2-weighted two- and three-dimensional fast spin-echo sequences (2D- and 3D-FSE, respectively) for a group of small breed dogs with thoracolumbar IVDD. Inclusion criteria were dogs with IVDD that underwent 1.5-Tesla MRI using both 2D-FSE and 3D-FSE sequences. For each dog and sequence, five pathologic indices were recorded: epidural fat discontinuation, vertebral canal compromise, spinal cord signal change, disc degeneration, and nerve root compression. Two independent investigators also scored visibility of the facet joint, intervertebral foramen, nerve roots, spinal cord grey-white matter differentiation, intervertebral discs, and epidural fat. The Wilcoxon signed-rank test was used to evaluate the between-sequence differences in pathologic indices and visibility scores. Interobserver agreement was measured using Cohen's weighted kappa along with 95% confidence intervals. A total of 21 dogs were sampled. The 3D-FSE sequences had higher pathologic indices of vertebral canal compromise (P=0.020) and spinal cord signal change (P=0.046) than 2D-FSE sequences. Furthermore, 3D-FSE sequences had higher visibility scores for the facet joint, intervertebral foramen, and nerve root structures (P<0.001). Findings from the current supported the use of 3D-FSE sequences over 2D-FSE sequences for the evaluation of IVDD and visualization of spinal structures in small breed dogs.

ESTUDO DO DIÂMETRO DO CORREDOR OBLÍQUO EM DECÚBITO LATERAL E DECÚBITO DORSAL: ESTUDO RADIOLÓGICO

ABSTRACT Introduction: Degenerative intervertebral disc disease and its impact on quality of life when associated with sagittal misalignmentis a current topic in the literature. The technique known as OLIF derives from the need to use anterior cage stop romote stabilization of the affected segment, indirect decompression, restoration of segmental lordosis, and sagittal balance. Methods: Single-center, non-randomized, comparative, observational study. The following variables were measured using magnetic resonance imaging of the lumbar spine in dorsal and lateral decubitus, establishing a comparison between the size of the OLIF corridor in the L3L4 and L4L5 segments, as well as a comparison of corridor size between the different positions. Results: There was no difference incorridor size in the comparison between decubitus. However, when the L3L4 and L4L5 levels were compared, there was a significant difference in the size of the corridor in both the lateral and dorsal positions. Conclusion: The present study did not show any difference between the size of the OLIF corridor in L3L4 and L4L5 in the different decubitus, suggesting that thee valuation of the corridor in convention al magnetic resonance images appearstobe safe andreflects the actual size when positio ned for performing the OLIF technique. Level of evidence III; Retrospective study.

Risk factors of unsatisfactory outcomes after percutaneous laser decompression of lumbar intervertebral discs

To study the risk factors of unsatisfactory clinical results after percutaneous laser decompression of the lumbar intervertebral disc (PLDD). A retrospective observational single-center study included medical records of patients who underwent lumbar PLDD for degenerative spine disease. We analyzed clinical and instrumental parameters potentially affecting the results of lumbar PLDD. Clinical study included 82 patients who underwent PLDD for lumbar intervertebral disc degenerative disease. Mean postoperative follow-up period was 30.8±13.3 months. In 22 (26%) patients, unsatisfactory clinical outcomes were observed. According to binary logistic regression model, comorbidities (p=0.03), duration of disease over 12 months (p=0.03), low preoperative quality of life according to ODI score (more than 50%) (p=0.04), high body mass index (over 25 kg/m2) (p=0.02), severe intervertebral disc (p=0.04) and facet joint degeneration (p=0.01) and intervertebral disc height decrease more than 50% (p=0.01) were significantly associated with unsatisfactory clinical outcomes after lumbar PLDD for degenerative spine disease. Identification of these risk factors of unsatisfactory clinical outcomes is important stage of preoperative preparation in patients scheduled for lumbar PLDD.

The experimental study of regeneration of annulus fibrosus using decellularized annulus fibrosus matrix/poly(ether carbonate urethane)urea-blended fibrous scaffolds with varying elastic moduli.

Although tissue engineering has attracted increasing attention for the treatment of degenerative intervertebral disc disease, the biochemical properties, structural organization, and mechanical characteristics of annulus fibrosus tissue have restricted progress. Differentiation of annulus fibrosus-derived stem cells (AFSCs) can be regulated by the elasticity of substrates such as poly(ether carbonate urethane)urea (PECUU). Decellularized annulus fibrosus matrix (DAFM) has good biocompatibility and biodegradability, making it suitable for cell adhesion, proliferation, and differentiation. In this study, we used a coaxial electrospinning method to synthesize DAFM/PECUU-blended fibrous scaffolds with elasticities approximating that of native inner and outer annulus fibrosus tissue. AFSCs cultured on DAFM/PECUU-blended fibrous scaffolds exhibited increased collagen type I gene expression with increasing elasticity of the scaffold material; notably, collagen type II and aggrecan gene expression exhibited the opposite trend. Regarding extracellular matrix secretion, collagen type I content gradually increased with substrate elasticity, while collagen type II and aggrecan contents decreased. In vivo evaluations employing magnetic resonance imaging, hematoxylin and eosin staining, and immunohistochemistry indicated that DAFM/PECUU-blended fibrous scaffolds could effectively repair defects of annulus fibrosus tissue. Our findings provide a theoretical and practical basis for the development of bionic annulus fibrosus tissue that closely mimics the biological properties, mechanical function, and matrix composition of native tissue.

Analysis of in-hospital analgesic pharmacotherapy costs and regimen and impact on postoperative pain-related function in degenerative lumbar intervertebral disc disease

BackgroundPain medication may affect clinical and economic outcomes, and a detailed description of pain medication use is advocated in the literautre for better assessment of clinical outcomes of spine surgery, which otherwise clould be misleading. ObjectivesTo analyze the impact of in-hospital analgesic pharmacotherapy after spine surgery on subjective quality of life and pain relief in patients with degenerative lumbar intervertebral disc disease (DLIVD), and also to analyze pharmacotherapy costs. DesignA single-center study included 50 patients with L5/S1 or L4/L5 DLIVD, eligible for spine surgery. InterventionNeurosurgery for DLIVD. Main endpointsOutcomes in terms of postoperative pain and function were recorded prospectively using standardized questionnaires. Data for cost analysis and pharmcotherapy regimen were obtained retrospectively from case histories, doctors’ request cards and hospital discharge summaries. ResultsMean total pharmacotherapy cost amounted to €453.42±49.09. Mean pharmacotherapy cost amounted to €314.76±54.21 preoperatively, and €138.66±25.54 postoperatively. The greatest improvement in function and quality of life was in patients treated with non-opioids. ConclusionThis study supports the notion that analgesic pharmacotherapies could be differentiated in terms of overall impact on quality of life, and that pain-related distress might be the most relevant factor in this setting.

CircSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3

The abnormal expression of circular RNAs (circRNAs) is associated with numerous human diseases. This study investigated the mechanism by which circRNA acts as competitive endogenous RNA in the regulation of degenerative intervertebral disc disease (IVDD). Decreased expression of circSPG21 was detected in degenerated nucleus pulposus cells (NPCs), the function of circSPG21 in NPCs was explored and verified, and the downstream target of circSPG21 was investigated. The interaction between circSPG21 and miR-1197 and its target gene (ATP1B3) was studied by online database prediction and molecular biological verification. Finally, the circSPG21/miR-1197/ATP1B3 axis was verified in the mouse tail-looping model. The expression of circSPG21 in the nucleus pulposus in IVDD was directly related to an imbalance of anabolic and catabolic factors, which affected cell senescence. circSPG21 was found to play a role in human NPCs by acting as a sponge of miR-1197 and thereby affecting ATP1B3. The regulation of circSPG21 provides a potentially effective therapeutic strategy for IVDD.

The Ultrasonic Electrical Stimulation Treating Recent Pain after Minimally Invasive Intervention with Disc Degenerative Diseases

Objective:To explore the analgesic effect of ultrasonic electrical stimulation for recent pain after minimally invasive interventional therapy for intervertebral disc degenerative diseases (DDD). Methods:From January to August 2019, 130 patients with DDD who were treated by minimally invasive intervention of intervertebral disc, and then were randomly divided into electrical stimulation group and conservative treatment group. After minimally invasive intervention, the electrical stimulation group was treated by ultrasonic electrical stimulation once a day for 7 days. The conservative treatment group was treated with conventional acupuncture and massage once a day for 3 days.The pain degree of before treatment and 3 days, 7 days and 1 month(m) after treatment were evaluated by pain numberical rating scale (NRS), the curative effect of 1 m post-cure was evaluated by NRS weighting method. Results:There was no significant difference of NRS score between the two groups before treatment (P &gt; 0.05). NRS of electrical stimulation group were significant lower than those in conservative treatment group, which was evaluated at several time point for 3 days, 7 days and one month after treatment (P &lt; 0.001). The curative effect of electrical stimulation group on one month after interventional treatment was significantly higher than that of conservative treatment group (P &lt; 0.001). Conclusion:The therapeutic effect of ultrasonic electrical stimulation is better than that of traditional acupuncture and massage for recent pain after minimally invasive interventional therapy with DDD, it is worthy to popularize in clinical treatment. Key words: After interventional therapy with DDD; The recent pain; ultrasonic electrical stimulation

Inverse Agonist of Retinoid-Related Orphan Receptor-Alpha Prevents Apoptosis and Degeneration in Nucleus Pulposus Cells via Upregulation of YAP.

Intervertebral disc degenerative disease (IDD) is the most common degenerative spine disease, which leads to chronic low back pain and symptoms in the lower extremities. In this study, we found that RORα, a member of the retinoid-related orphan receptor family, is significantly elevated in nucleus pulposus tissue in IDD patients. The elevation of RORα is associated with increased apoptosis of nucleus pulposus (NP) cells. Therefore, we applicated a well-established inverse agonist of RORα, SR3335, to investigate its role in regulating NP cell metabolism and apoptosis. To further investigate the mechanism that SR3335 regulates the pathogenesis of IDD in vitro, tumor necrosis factor alpha (TNF-α) stimulation was used in human NP cells to mimic the hostile environment that leads to degeneration. We found that SR3335 treatment reversed the trend of increased apoptosis in NP cells induced by TNF-α treatment. Next, TNF-α treatment upregulated the expression of type II collagen and aggrecan and downregulated MMP13 (matrix-degrading enzyme matrix metalloproteinase 13) and ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4). However, these effects were reversed after SR3335 treatment. Furthermore, we find that SR3335 mediated the effect in NP cells by regulating the YAP signaling pathway, especially by affecting the phosphorylation state of YAP. In conclusion, the reduction of matrix degradation enzymes and apoptosis upon SR3335 treatment suggests that SR3335 is a promising drug in reversing the deleterious microenvironment in IDD patients.

Effect of Transforming Growth Factor Beta (TGF-β) on the Degeneration of Intervertebral Discs by Regulating Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells/Mammalian Target of Rapamycin (NF-fcB/mTOR) Signaling Pathway

Intervertebral disc degenerative disease (IDDD) is common in orthopedics. TGF-β involves in inflammation and tissue repair. But its role in IDDD remains unclear. IDDD patients and normal intervertebral disc nucleus pulposus tissues were collected. IDDD was divided into prominent group and prolapse group. IDDD nucleus pulposus cells were isolated and divided into control group, TGF-β agonist group and TGF-β inhibitor group followed by analysis of cell proliferation by MTT, cell apoptosis by flow cytometry BALP and OC expression by Real time PCR, NF-/&lt;B/mTOR signaling protein expression by Western blot as well as IL-1 and IL-6 secretion by ELISA. Compared with normal group, TGF-β mRNA and serum level in patients with IDDD was significantly decreased (P &lt; 0.05), with more significant changes in prolapse group (P &lt; 0.01). Pfirrmann grading scores were negatively correlated with TGF-β serum level (P &lt; 0.001). TGF-β agonists can significantly promote cell proliferation, inhibit apoptosis, upregulate BALP and OC expression, inhibit NF-κB expression, increased p-mTOR level and decrease IL-1 and IL-6 secretion (P &lt; 0.05). All these changes were significantly reversed by TGF-β inhibitors (P &lt; 0.05). TGF-β expression in IDDD is reduced and associated with disease severity. Promoting TGF-β expression can inhibit inflammatory factors secretion, promote BALP and OC expression and cell proliferation, and inhibit the degeneration of intervertebral discs by regulating NF-/&lt;B/mTOR signaling.

Establishment of a New Model of Lumbar Intervertebral Disc Degeneration With Pathological Characteristics.

A prospective study. Intervertebral disc degenerative disease is a common and frequently-occurring disease in adults and is the main cause of lower back pain. However, there is a lack of universal animal models to study disc degeneration. Forty-two male New Zealand white rabbits aged 12 months were used in this study. We established an endplate ischemic disc degeneration model though surgical ligation of rabbit lumbar vertebral body segment arteries. Two weeks after surgery, 6 experimental animals were randomly selected for follow-up tests. First, ischemia and lumbar disc degeneration were confirmed using imaging techniques. Then, immunohistochemical staining was performed to observe the growth of the annulus fibrosus. Finally, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting were used to detect mRNA expression and protein content of IL-1α, TNFα, collagen II, MMP-3, aggrecan, and PLA2 in the nucleus pulposus of the disc. Imaging examination confirmed the successful construction of a lumbar disc degeneration model. Histological analysis and biochemical analysis showed a damaged intervertebral disc structure, and collagen II and aggrecan, the key extracellular matrix components of intervertebral discs, were reduced in synthesis and content. The synthesis and expression of IL-1α, TNFα, PLA2, and MMP-3 related to disc catabolism and inflammatory response were enhanced. We successfully constructed a lumbar disc degeneration ischemia model, which provides a novel approach to study the pathological mechanisms involved in discogenic low back pain and to prevent and treat discogenic low back pain.

Recent advances of hydrogel-based biomaterials for intervertebral disc tissue treatment: A literature review.

Low back pain is an increasingly prevalent symptom mainly associated with intervertebral disc (IVD) degeneration. It is highly correlated with aging, as the nucleus pulposus (NP) dehydrates and annulus fibrosus fissure formatting, which finally results in the IVD herniation and related clinical symptoms. Hydrogels have been drawing increasing attention as the ideal candidates for IVD degeneration because of their unique properties such as biocompatibility, highly tunable mechanical properties, and especially the water absorption and retention ability resembling the normal NP tissue. Numerous innovative hydrogel polymers have been generated in the most recent years. This review article will first briefly describe the anatomy and pathophysiology of IVDs and current therapies with their limitations. Following that, the article introduces the hydrogel materials in the classification of their origins. Next, it reviews the recent hydrogel polymers explored for IVD regeneration and analyses what efforts have been made to overcome the existing limitations. Finally, the challenges and prospects of hydrogel-based treatments for IVD tissue are also discussed. We believe that these novel hydrogel-based strategies may shed light on new possibilities in IVD degeneration disease.

Lower Plasma Melatonin in the Intervertebral Disk Degeneration Patients Was Associated with Increased Proinflammatory Cytokines.

BackgroundIntervertebral disc degeneration (IDD) was considered to be the pathological basis of intervertebral disc herniation (IDH). However, the plasma melatonin in the IDD cases and healthy controls remained unclear.MethodsIn this case–control study, a total of 71 IDD cases and 54 healthy controls were enrolled between April 2020 and August 2020. The diagnostic effect of plasma melatonin for IDD was detected using receiver operating characteristic curve. The correlations between two continuous variables were detected with the Pearson linear analyses.ResultsIt was found that lower melatonin concentration was detected in the IDD cases (1.906 ± 1.041 vs 3.072 ± 0.511 pg/mL, P<0.001). Through receiver operating characteristic curve analyses, it was found that plasma melatonin could be used as a diagnostic biomarker for IDD (area under curve=0.808, P<0.001). In advanced correlation analyses, it was found that plasma melatonin concentration was negatively associated with the age, symptom durations, IDD disease severity and proinflammatory factors, including IL-6 and TNF-α concentrations (P<0.05). Comparing with the higher melatonin groups, significantly increased IL-6 (0.601 ± 0.085 vs 0.507 ± 0.167 pg/mL, P=0.028) and TNF-α (3.022 ± 0.286 vs 2.353 ± 0.641, P<0.001) were detected in the patients with lower melatonin concentration.ConclusionThe plasma melatonin concentration was significantly decreased in the IDD cases and plasma melatonin could be used as a diagnostic biomarker for IDD. Lower plasma melatonin was associated with longer disease durations, elevated disease severity and higher inflammatory cytokines levels in IDD patients.

Crosstalk between Autophagy and Apoptosis in Intervertebral Disc Degeneration

Objective: To describe the relationship between autophagy and apoptosis and the possible signaling pathways involved in degenerative lumbar intervertebral disc. Summary of Background Data: Autophagy and apoptosis are regulatory cellular mechanisms that determine many pathologies, including degenerative intervertebral disc disease. The interactions between these events in the damage or protection of intervertebral disc cells and in cellular homeostasis remain controversial. Methods: The sample size was twenty patients who underwent lumbar spine surgery for symptomatic disc herniation or spondylolisthesis. Intervertebral discs were classified by magnetic resonance as Pfirrmann grade IV and grade V. Six patients were operated on two levels, resulting in twenty-six intervertebral discs that were submitted to immunohistochemistry to verify the protein expression of autophagy and apoptosis markers. Results: The autophagic markers had greater protein expression in the human intervertebral disc (Pfirrmann Grades IV and V). Under these conditions, autophagy and apoptosis showed a negative correlation. Regarding apoptosis, caspase 8 presented the highest protein expression, which allows inferring the preference for the extrinsic pathway in cell death. Conclusions: Autophagy had the greatest protein expression negative profile compared to apoptosis. Caspase 8 had the highest protein expression in apoptosis.

The c-Jun signaling pathway has a protective effect on nucleus pulposus cells in patients with intervertebral disc degeneration.

Among a range of diverse clinical symptoms, intervertebral disc degeneration (IDD) contributes mostly to the onset of lower back pain. The present study aimed to investigate the effects of c-Jun on nucleus pulposus (NP) cells of IDD and its regulation on molecular mechanisms. Intervertebral disc (IVD) tissues were collected from patients suffering from IDD disease, and NP cells were subsequently isolated and cultured. By overexpressing c-Jun in NP cells, expression levels of mRNAs and proteins of IDD-related genes and inflammatory cytokines were subjected to reverse transcription-quantitative PCR, western blot and ELISA assays. Additional transforming growth factor-β (TGF-β) antibodies were administrated to suppress the function of TGF-β. Cell proliferation and apoptosis were determined via Cell Counting Kit-8 and TUNEL assays, respectively. The results demonstrated that the overexpression of c-Jun robustly upregulated both mRNA and protein expression of TGF-β, TIMP metallopeptidase inhibitor 3, aggrecan and collagen type II alpha 1 chain and simultaneously downregulated the expression of the inflammatory cytokines TNF-α, interleukin (IL)-1β, IL-6 and IL-17. Furthermore, following c-Jun overexpression, survival rates of NP cells were increased while apoptosis rates were decreased. However, the addition of a TGF-β antibody significantly promoted apoptosis and restricted cell survival, which differed from the results of the c-Jun overexpression group. The present study hypothesized therefore that c-Jun may positively regulate TGF-β expression within NP cells of IDD, which could promote the proliferation of IDD-NP cells and accelerate cell viability via reducing apoptosis and the inflammatory response.

Regeneration of annulus fibrosus tissue using a DAFM/PECUU-blended electrospun scaffold

Low back pain and disc degeneration affect quality of life and imposes an enormous financial burden. Although annulus fibrosus (AF) tissue engineering provides an alternative therapeutic possibility in the treatment of degenerative intervertebral disc disease, it is restricted by the biochemical properties, organizational structure, and mechanical characteristics of the scaffold. The ideal scaffold should closely mimic the natural extracellular matrix (ECM) in structure and function for long-term stability and survival. Poly(ether carbonate urethane) urea (PECUU) can be electrospun into nanofibrous scaffolds to mimic ECM architecture with the appropriate mechanical properties. However, PECUU scaffolds lack the bioactivity of natural ECM. On the other hand, a decellularized annulus fibrosus matrix (DAFM) has good biocompatibility and biodegradability and has been shown to promote secretion of AF-related ECM. Herein, DAFM/PECUU-blended electrospun scaffolds were fabricated with the help of coaxial electrospinning technology for the first time. AF-derived stem cells were cultured on DAFM/PECUU electrospun scaffolds, and cellular metabolic activity, morphology, and gene expression assays as well as AF-related ECM synthesis were performed. The results showed that AF-derived stem cells proliferated well on the scaffolds. Gene expression and ECM secretion of collagen type I and II and aggrecan from AF-derived stem cells cultured on DAFM/PECUU electrospun scaffolds were higher than from those on PECUU fibrous scaffolds. Thus, DAFM/PECUU electrospun scaffolds are a potential candidate for AF tissue engineering applications.

Exosomes derived from stem cells as an emerging therapeutic strategy for intervertebral disc degeneration.

Intervertebral disc (IVD) degenerative diseases are a common problem in the world, and they cause substantial social and economic burdens for people. The current methods for treating IVD degenerative diseases mainly include surgery and conservative treatment, which cannot fundamentally restore the normal structure of the disc. With continuous research on the mechanism of degeneration and the development of regenerative medicine, rapid progress has been made in the field of regenerative medicine regarding the use of stem cell-derived exosomes, which are active biological substances used in intercellular communication, because they show a strong effect in promoting tissue regeneration. The study of exosomes in the field of IVD degeneration has just begun, and many surprising achievements have been made. This paper mainly reviews the biological characteristics of exosomes and highlights the current status of exosomes in the field of IVD degeneration, as well as future developments regarding exosomes.