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Intervertebral disc degeneration (IVDD) is a degenerative disease accompanied by the loss of nucleus pulposus cells and the degradation of extracellular matrix (ECM), which tends to be associated with lower back pain. The ECM and various types of cell death in IVDD are regulated by multiple factors, such as inflammatory responses and oxidative stress. The glutathione (GSH) redox system is the most important antioxidant defense system in cells. GSH is one of the most abundant thiol antioxidants in mammalian cells, which functions directly and indirectly by scavenging peroxides through the GSH redox system. In these reactions, GSH is oxidized by electrophilic substances, such as reactive oxygen species and free radicals, to form glutathione disulfide to exert antioxidative effects. It has been reported that GSH can protect cells against the damage of oxidative stress and various pathophysiological stimulus that can lead to different types of cell death. In addition, it was reported that the level of GSH widely participates in apoptosis, autophagy, ferroptosis, and oxidative stress in many diseases including osteoarthritis and IVDD. Therefore, we summarized the effects of GSH on ECM metabolism and cells' functions during IVDD. In addition, we summarized the regulatory effects of small molecule compounds on GSH to explore potential ways to regulate the level of GSH. Better understanding the underlying role of GSH in regulating IVDD will facilitate the goal of preventing and retarding the progress of IVDD in the future., Competing Interests: No conflicts of interest need to be explained., (Copyright © 2024 Fudong Li et al.)

Purposes: To propose a new lumbar degenerative staging system using the current radiological classification system., Methods: A cross-sectional analysis of retrospective databases between January 2018 and December 2022 was performed. Total of 410 patients for Modic changes, paravertebral muscle fat infiltration, disc degeneration, articular process degeneration, vertebral endplate degeneration and other structures, and disc displacement, Spondylolisthesis, and stenosis, and grouped patients according to stage were assessed. Visual analog scale, Japanese Orthopaedic Association, and Oswestry Disability Index scores were used to assess low back pain strength, neurological function, and quality of life, respectively., Results: The lumbar degeneration staging system consists of 8 variables, which can be divided into 3 steps: early, middle and late, and the correlation between each variable is strong (P < 0.05). The later the staging, the worse the Japanese Orthopaedic Association, visual analog scale, and Oswestry Disability Index scores., Conclusions: Patients with later stages have worse clinical scores. This staging system recommends a uniform classification to assess lumbar degeneration., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Low back pain resulting from intervertebral disc degeneration (IVDD) is a prevalent global concern; however, its underlying mechanism remains elusive. Single-cell sequencing analyses revealed the critical involvement of pyroptosis in IVDD. Considering the involvement of reactive oxygen species (ROS) as the primary instigator of pyroptosis and the lack of an efficient intervention approach, this study developed carbonized Mn-containing nanodots (MCDs) as ROS-scavenging catalytic biomaterials to suppress pyroptosis of nucleus pulposus (NP) cells to efficiently alleviate IVDD. Catalytic MCDs have superior efficacy in scavenging intracellular ROS and rescuing homeostasis in the NP microenvironment compared with N-acetylcysteine, a classical antioxidant. The data validates that pyroptosis plays a vital role in mediating the protective effects of catalytic MCDs against oxidative stress. Systematic in vivo assessments substantiate the effectiveness of MCDs in rescuing a puncture-induced IVDD rat model, further demonstrating their ability to suppress pyroptosis. This study highlights the potential of antioxidant catalytic nanomedicine as a pyroptosis inhibitor and mechanistically unveils an efficient strategy for the treatment of IVDD., (© 2024 Wiley‐VCH GmbH.)

Neuromodulation-related intervertebral disc degeneration (IVDD) is a novel IVDD pattern and are proposed recently. However, the mechanistic basis of neuromodulation and intervertebral disc (IVD) homeostasis remains unclear. Here, this study aimed to investigate the expression of postganglionic sympathetic nerve fiber-derived vasoactive intestinal peptide (VIP) system in human IVD tissue, and to assess the role of VIP-related neuromodulation in IVDD. Patient samples and in vitro cell experiments showed that the expression of receptors for VIP is negatively correlated with the severity of IVDD, and the administration of exogenous VIP can ameliorate interleukin 1β-induced nucleus pulposus (NP) cell apoptosis and inflammation. Further mRNA-seq analysis revealed that fibroblast growth factor 18- (FGF18)-mediated activation of V-akt murine thymoma viral oncogene homolog signaling pathway is involved in the protective effects of VIP on inflammation-induced NP cell degeneration. Further analysis identified VIP via its receptor vasoactive intestinal peptide receptor 2 can directly result in decreased expression of miR-15a-5p, which targeted FGF18. Finally, in vivo mice lumbar IVDD model confirmed that focally exogenous administration of VIP can effectively ameliorated the progression of IVDD, as shown by the radiological and histological analysis. In conclusion, these results indicated that sympathetic neurotransmitter, VIP, delayed IVDD via FGF18/FGFR2-mediated activation of V-akt murine thymoma viral oncogene homolog signaling pathway, which will broaden the horizon concerning how the neuromodulation correlates with IVDD and shed new light on novel therapeutical alternatives to IVDD., (© 2023 Wiley-VCH GmbH.)

Intervertebral disc degeneration (IVDD) is a prevalent and debilitating condition characterized by chronic back pain and reduced quality of life. Strontium ranelate (SRR) is a compound traditionally used for treating osteoporosis via activating TGF-β1 signaling pathway. Recent studies have proved the anti-inflammatory effect of SRR on chondrocytes. Although the exact mechanism of IVDD remains unclear, accumulating evidences have emphasized the involvement of multifactorial pathogenesis including inflammation, oxidative stress damage, and etc. However, the biological effect of SRR on IVDD and its molecular mechanism has not been investigated. Firstly, this study proved the decreased expression of Transforming Growth Factor-beta 1(TGF-β1) in degenerated human intervertebral disc tissues. Subsequently, we confirmed for the first time that SRR could promote cell proliferation, mitigate inflammation and oxidative stress in human nucleus pulposus cells in vitro via increasing the expression of TGF-β1 and suppressing the Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) pathway. The molecular docking result proved the interaction between SRR and TGF-β1 protein. To further verify this interaction, gain- and loss- of function experiments were conducted. We discovered that both TGF-β1 knockdown and overexpression influenced the activation of the NF-κB pathway. Taken together, SRR could mitigate IL-1β induced-cell dysfunction in human nucleus pulposus cells by regulating TGF-β1/NF-κB axis in vitro . Finally, the in vivo therapeutic effect of SRR on IVDD was confirmed. Our findings may contribute to the understanding of the complex interplay between inflammation and degenerative processes in the intervertebral disc and provide valuable insights into the development of targeted treatment-based therapeutics for IVDD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be, therefore, enlightening that investigating the exact pathogenesis of IVDD and developing target-specific molecular drugs in the future. Ferroptosis is a new form of programmed cell death characterized by glutathione (GSH) depletion, and inactivation of the regulatory core of the antioxidant system (glutathione system) GPX4. The close relationship of oxidative stress and ferroptosis has been studied in various of diseases, but the crosstalk between of oxidative stress and ferroptosis has not been explored in IVDD. At the beginning of the current study, we proved that Sirt3 decreases and ferroptosis occurs after IVDD. Next, we found that knockout of Sirt3 (Sirt3 -/- ) promoted IVDD and poor pain-related behavioral scores via increasing oxidative stress-induced ferroptosis. The (immunoprecipitation coupled with mass spectrometry) IP/MS and co-IP demonstrated that USP11 was identified to stabilize Sirt3 via directly binding to Sirt3 and deubiquitinating Sirt3. Overexpression of USP11 significantly ameliorate oxidative stress-induced ferroptosis, thus relieving IVDD by increasing Sirt3. Moreover, knockout of USP11 in vivo (USP11 -/- ) resulted in exacerbated IVDD and poor pain-related behavioral scores, which could be reversed by overexpression of Sirt3 in intervertebral disc. In conclusion, the current study emphasized the importance of the interaction of USP11 and Sirt3 in the pathological process of IVDD via regulating oxidative stress-induced ferroptosis, and USP11-mediated oxidative stress-induced ferroptosis is identified as a promising target for treating IVDD., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2023. Published by Elsevier B.V.)

Background: Intervertebral disc degeneration (IDD) is a complex phenomenon and a multifactorial degenerative disease that creates a heavy economic burden on health systems globally. Currently, there is no specific treatment proven to be effective in reversing and delaying the progression of IDD., Method: This study consisted of animal and cell culture experiments. The role of DNA methyltransferase 1 (DNMT1) on regulating the M1/M2 macrophages polarization and pyroptosis, as well as its effect on Sirtuin 6 (SIRT6) expression in an IDD rat model and in tert-butyl hydroperoxide (TBHP)-treated nucleus pulposus cells (NPCs) were explored. Rat models were constructed, followed by transfection with lentiviral vector to inhibit DNMT1 or overexpress SIRT6. The NPCs were treated with THP-1-cells conditioned medium, and their pyroptosis, apoptosis, and viability were evaluated. Western blot, histological and immunohistochemistry staining, ELISA, PCR, and flow cytometry were all used to evaluate the role of DNMT1/ SIRT6 on macrophage polarization., Results: Silencing DNMT1 inhibited apoptosis, the expression of related inflammatory mediators (e.g., iNOS) and inflammatory cytokines (e.g., IL6 and TNF-α). Moreover, silencing DNMT1 significantly inhibited the expression of pyroptosis markers IL- 1β, IL-6, and IL-18 and decreased the NLRP3, ASC, and caspase-1 expression. On the other hand, M2 macrophage specific markers CD163, Arg-1, and MR were overexpressed upon silencing DNMT1 or SIRT6 overexpression. At the same time, silencing DNMT1 exerted a regulatory effect on increasing the SIRT6 expression., Conclusions: DNMT1 may be a promising potential target for IDD treatment due to its ability to ameliorate the progression of the disease.

Intervertebral disc degeneration (IVDD), a widely known contributor to low back pain (LBP), has been proved to be a global health challenging conundrum. Hesperidin (hesperetin-7-O-rutinoside, HRD) is a flavanone glycoside that belongs to the subgroup of citrus flavonoids with therapeutic effect on various diseases due to its anti-inflammatory, antioxidant properties. However, the effect of HRD on IVDD remains elusive. The human nucleus pulposus tissues were harvested for isolating human nucleus pulposus (HNP) cells to verify the expression of Nrf2. The biological effect of HRD on HNP cells were assessed in vitro, and the in vivo therapeutic effects of HRD were assessed in mice. Firstly, we found that the expression of Nrf2 was decreased with the progression of degeneration in degenerated human nucleus pulposus tissue. Subsequently, we confirmed that HRD could mitigate oxidative stress-induced ferroptosis in nucleus pulposus cells via enhancing the expression of Nrf2 axis and suppressing the NF-κB pathway to protect intervertebral disc from degeneration in vitro. Finally, the therapeutic effects of HRD were confirmed in vivo. The current study proved for the first time that HRD may protect HNP cells from degeneration by suppressing ferroptosis in an oxidative stress-dependent via enhancing the expression of Nrf2 and suppressing the NF-κB pathway. The evidence will provide a possible basis for future targeted treatment for IVDD.

Background: As an important part of spinal fusion procedure, the selection of fusion cage size is closely related to the curative effect of the surgery. It mainly depends on the clinical experience of surgeons, and there is still a lack of objective standards. The purpose of this study is to propose the concept of relative intervertebral tension (RIT) for the first time and its grading standards to improve the surgical procedures of lumbar interbody fusion., Methods: This retrospective study was conducted from January 2018 to July 2019. A total of 83 eligible patients including 45 men and 38 women with lumbar degenerative disease underwent transforaminal lumbar interbody fusion (TLIF) were included in this study. A total of 151 fusion segments were divided into group A, group B and group C according to the grading standards of RIT. In addition, parameters of intervertebral space angle (ISA), intervertebral space height (ISH), intervertebral space foramen (IFH), fusion rates, cage-related complications and cage heights were also compared among the three groups., Results: The ISA in group A was the smallest among three groups in contrast with group C with largest ISA at the final follow-up(P < 0.05). The group A presented the smallest ISH and IFH values(P < 0.05), compared with group B with the largest ISH and IFH values(P < 0.05). These two parameters in the group C were in-between. The fusion rates of group A, group B and group C were 100%, 96.3% and 98.8% at the final follow-up, respectively. No statistical difference in fusion rates and cage-related complications occurred among the three groups(P > 0.05), and a certain correlation between ISH and RIT was also observed., Conclusions: The concept of RIT and the application of its clinical grading standards could simplify the surgical procedures of spinal fusion and reduce cage-related complications., (© 2023. The Author(s).)

Intervertebral disc degeneration (IVDD) has been the major contributor to chronic lower back pain (LBP). Abnormal apoptosis, senescence, and pyroptosis of IVD cells, extracellular matrix (ECM) degradation, and infiltration of immune cells are the major molecular alternations during IVDD. Changes at tissue level frequently occur at advanced IVD tissue. Ectopic ingrowth of nerves within inner annulus fibrosus (AF) and nucleus pulposus (NP) tissue has been considered as the primary cause for LBP. Innervation at IVD tissue mainly included sensory and sympathetic nerves, and many markers for these two types of nerves have been detected since 1940. In fact, in osteoarthritis (OA), beyond pain transmission, the direct regulation of neuropeptides on functions of chondrocytes have attracted researchers' great attention recently. Many physical and pathological similarities between joint and IVD have shed us the light on the neurogenic mechanism involved in IVDD. Here, an overview of the advances in the nervous system within IVD tissue will be performed, with a discussion on in the role of nerve fibers and their neurotransmitters in regulating IVDD. We hope this review can attract more research interest to address neuromodulation and IVDD itself, which will enhance our understanding of the contribution of neuromodulation to the structural changes within IVD tissue and inflammatory responses and will help identify novel therapeutic targets and enable the effective treatment of IVDD disease., Competing Interests: Competing interests The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Intervertebral foramen endoscopy has developed rapidly, but compared with transforaminal lumbar interbody fusion (TLIF), the progress of degeneration is unknown. We aim to compare the changes of intervertebral disc and intervertebral foramen in adjacent segments after TLIF and endoscopic discectomy for patients with lumbar disc herniation (LDH)., Methods: From 2014 to 2017, 87 patients who were diagnosed with single-level LDH and received surgery of TLIF (group T, n = 43) or endoscopic discectomy (group F, n = 44) were retrospectively analyzed. X-ray, MRI, CT and clinical symptoms were recorded before operation and at the last follow-up (FU). The neurological function was originally evaluated by the Japanese Orthopaedic Association (JOA) scores. Radiological evaluation included the height of intervertebral space (HIS), intervertebral foramen height (FH), intervertebral foramen area (FA), lumbar lordosis (CA) and intervertebral disc degeneration Pfirrmann scores., Results: There was no significant difference in baseline characteristics, JOA improvement rate, reoperation rate and complications between the two groups. The age, average blood loss, average hospital stays and average operation time in group F were lower than those in group T. During the last FU, HIS, CA and FA decreased in both groups, and the changes in group T were more significant than those in group F (P < .05). There was no significant difference in FH changes between the two groups (P > .05)., Conclusion: Both TLIF and endoscopic surgery can achieve good results in the treatment of LDH, but the risk of lumbar disc height loss and intervertebral foramina reduction in the adjacent segment after endoscopic surgery is lower., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Intervertebral disc degeneration (IVDD) has been a complex disorder resulted from genetic and environmental risk factors. The aim of this study was to identify the risk factors associated with IVDD in orthopaedic patients and develop a prediction model for predicting the risk of IVDD. A total of 309 patients were retrospectively included in the study and randomly divided into the training group and the validation group. The least absolute shrinkage and selection operator regression (LASSO) and the univariate logistic regression analysis were used to optimize factors selection for the IVDD risk model. Multivariable logistic regression analysis was used to establish a predicting nomogram model incorporating the factors. In addition, discrimination, calibration, and clinical usefulness of the nomogram model were evaluated via the C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). Then, based on the results above, the relationship between IVDD and angiotensin II (AngII) level in peripheral blood was examined prospectively. The predictors of the nomogram include age, sex, hypertension, diabetes, gout, working posture, and exercising hours per week. The C -index values of the training and validation groups were 0.916 (95% CI, 0.876-0.956) and 0.949 (95% CI, 0.909-0.989), respectively, which indicated that the model displayed good discrimination. In addition, the area under the curve (AUC) values of the ROC curve of the training and the validation group were 0.815 (95% CI, 0.759-0.870) and 0.805 (95% CI, 0.718-0.892), respectively, revealing the satisfactory discrimination performance of the model. The prospective investigation showed that the average AngII level in the degenerated group (97.62 ± 44.02 pg/mL) was significantly higher than that in the nondegenerated group (52.91 ± 9.01 pg/mL) ( p < 0.001). This present study explored the risk factors for IVDD and established a prediction model, which would effectively predict the risk of IVDD. In addition, based on the prediction model, AngII was revealed to be a potentially auxiliary clinical diagnostic marker for IVDD., Competing Interests: We declare there are no conflicts of interests., (Copyright © 2022 Fudong Li et al.)

Chronic low back pain (CLBP) has been proved to be the dominating cause of disability in patients with lumbar degenerative diseases. Of the various etiological factors, intervertebral disc degeneration (IVDD) has been the dominating cause. In the past few decades, the role and changes of nerve systems, especially the peripheral sensory fibers and their neurotransmitters, in the induction and progression of IVDD have attracted growing concerns. The expression of many neuropeptides, such as SP, NPY, and CGRP, in the nociceptive pathways is increased during the progression of IVDD and responsible for the discogenic pain. Here, the role of CGRP in the progression of IVDD was firstly investigated both in vitro and in vivo. Firstly, we confirmed that human degenerated intervertebral disc tissue exhibited elevated expression of CGRP and its receptor. Secondly, in vitro experiments suggested that CGRP could inhibit the proliferation and induce apoptosis in human nucleus pulposus (NP) cells, as well as promote inflammation and degenerated phenotypes through activating NF- κ B and MAPK signaling pathways. Thirdly, CGRP receptor antagonist, Rimegepant, can ameliorate the adverse effects of CGRP imposed on NP cells, which were confirmed in vitro and in vivo. Our results will bring about a brand-new insight into the roles of neuromodulation in IVDD and related therapeutic attempts., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Kaiqiang Sun et al.)

Lumbar intervertebral disc degeneration (IDD) has been the major contributor to low back pain (LBP). IDD is an chronic inflammation process, with the activation of plentiful inflammation-related cytokines and ECM degradation-related enzymes. In the past few years, hypertension has been reported to correlate with LBP. In addition, the local tissue renin-angiotensin system (tRAS) has been identified in multiple tissues, including the spinal cord, skin, kidney, heart, and bone. Recently, tRAS has also been established in both bovine and human intervertebral disc tissues, especially in the degenerated disc tissue. However, the exact of tRAS and IDD remains unknown. In this present study, proteomic analysis, molecular biology analysis, and animal model were all used. Firstly, we revealed that tRAS was excessively activated in the human degenerated intervertebral disc tissue via proteomic analysis and molecular biology analysis. Then, in vitro experiment suggested that Ang II could decrease the cell viability of human NP cells and promote NP cell apoptosis, senescence, oxidative stress, and NLRP3 activation in human NP cells. In addition, Ang II could also trigger degeneration and fibrosis phenotype in human NP cells. Finally, the animal model demonstrated that the local activated ACE/Ang II axis in the NP tissue could accelerate IDD in aging spontaneously hypertensive rats (SHR). Collectively, the degenerated intervertebral disc tissue showed excessively activated tRAS, and local activated tRAS could induce NP cell senescence, apoptosis, oxidative stress, and inflammatory reaction to promote IDD. These biological effects of Ang II on human NP cells may provide novel insight into further treatment of IDD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Kaiqiang Sun et al.)

Study Design: This is a prospective case-controlled study., Purpose: The purpose of this study is to investigate the effect of a modified transforaminal lumbar interbody fusion (TLIF) on the immediate post-operative symptoms in patients with lumbar disc herniation (LDH) accompanied with stenosis., Methods: A total of 204 LDH patients with single-level TLIF were enrolled. According to the sequence of the placement of rods and cage, patients were divided into group R (rod-prior-to-cage) and group C (cage-prior-to-rod). Neurological function was evaluated by the Japanese Orthopedic Association (JOA) score. Radiological assessment includes height of intervertebral space (HIS), foraminal height (FH), foraminal area (FA), and segmental lordosis (SL). Change of original symptoms (pain/numb) and new-onset symptoms (pain/numb) after surgery were also recorded., Results: Patients in group R had less change of HIS at L3/4, L4/5, and L5/S1 levels compared with pre-operation (all p > 0.05), whereas group C had larger change (all p < 0.05). No statistical difference was found in FH between the two groups before and after surgery at L3/4, L4/5, and L5/S1, respectively (all p > 0.05). In terms of FA, patients in group R had better improvement after surgery than those in group C at L3/4 and L4/5 (both p < 0.05). Patients in both groups acquired good improvement of neurological function. However, there were fewer patients in group R who experienced post-operative leg pain or numb compared with those in group C (p < 0.05)., Conclusion: The modified open TLIF can significantly reduce the incidence of immediate post-operative symptoms for patients with single-level lumbar disc herniation via installation of rods prior to insertion of cage and the "neural standard" should serve as the goal of decompression for spine surgeons to restore disc/foraminal height and to minimize nerve distraction.

Inflammation plays an essential role in the development of lumbar disc degeneration (LDD), although the exact effects of macrophage subtypes on LDD remain unclear. Based on previous studies, we hypothesized that M2-polarization of local macrophages and simultaneous suppression of their production of fibrotic transforming growth factor beta 1 (TGFβ1) could inhibit progression of LDD. Thus, we applied an orthotopic injection of adeno-associated virus (AAV) carrying shRNA for DNA Methyltransferase 1 (DNMT1) and/or shRNA for TGFβ1 under a macrophage-specific CD68 promoter to specifically target local macrophages in a mouse model for LDD. We found that shDNMT1 significantly reduced levels of the pro-inflammatory cytokines TNFα, IL-1β and IL-6, significantly increased levels of the anti-inflammatory cytokines IL-4 and IL-10, significantly increased M2 macrophage polarization, significantly reduced cell apoptosis in the disc degeneration zone and significantly reduced LDD-associated pain. The anti-apoptotic and anti-pain effects were further strengthened by co-application of shTGFβ1. Together, these data suggest that M2 polarization of macrophages induced by both epigenetic modulation and suppressed production and release of TGFβ1 from polarized M2 macrophages, may have a demonstrable therapeutic effect on LDD.

The functional changes of nucleus pulposus (NP) cells are considered to be the initiating factors of intervertebral disc degeneration (IDD), and the differentially expressed circRNAs in NP cells may play an important role in the process of IDD. To identify circular RNAs (circRNAs) associated with human IDD, we isolated the NP cells from human degenerated and non-degenerated intervertebral disc and identified NP cells by microscopy and cell proliferation. CircRNA microarray expression profiles were obtained from NP cells of degenerated and non-degenerated intervertebral disc and further validated by quantitative reverse transcription PCR (qRT-PCR). The expression data were analyzed by bioinformatics. Microarray analysis identified 7294 circRNAs differentially expressed in degenerated human IDD NP cells. Among them, 3724 circRNAs were up-regulated and 3570 circRNAs were down-regulated by more than 2 folds. After validating by qRT-PCR, we predicted the possible miRNAs of the top dysregulated circRNAs using TargetScan, and miRanda. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most modulated circRNAs regulate the viability, degradation, apoptosis and oxidative stress in NP cells, and the possible mechanism underlying IDD was discussed. These results revealed that circRNAs may play a role in IDD and might be a promising candidate molecular target for gene therapy., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Our aim was to investigate the biological effects of bone morphogenic protein 2 (BMP2) on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocyte-like cells in platelet-rich plasma (PRP) gel in vitro. In addition, the effectiveness of BMP2-transduced BMSCs in combined with PRP gel to repair the degenerated intervertebral disc in a rabbit model was also evaluated. Previous studies have shown that tissue engineering provides many promising advantages to treating disc degeneration and may reverse the pathological process of disc degeneration., Methods: The expressions of types I, II and X collagen, aggrecan and Sox9 of the BMP2-transduced BMSCs in monolayer or PRP gel were examined by reverse transcriptase polymerase chain reaction (RT-PCR). Sixty New Zealand white rabbits were divided into five groups: 12 normal controls; 12 puncture operated with only disc degeneration being induced; 12 PRP transplantation animals; 12 BMSC and PRP-transplantation animals; 12 BMP2-transduced BMSCs and PRP-transplantation animals. The effect of BMP2-transduced BMSCs on degenerated discs were evaluated by magnetic resonance image (MRI) scan, histology, immunohistochemistry and Western blot analysis., Results: BMP2 could facilitate chondrogenic differentiation of BMSCs in monolayer or PRP gel. The discs treated with BMP2-transduced BMSCs exhibited relatively well-preserved nucleus pulposus (NP) structure. Significantly higher T2-weighted signal intensity and a greater amount of extracellular matrix were observed in the BMP2-transduced BMSC group compared with other groups. In addition, the presences of BMP2-transduced BMSCs were identified at week 12 postoperatively in vivo., Conclusions: BMP2-transduced BMSCs can maintain the chondrocyte-like phenotype in PRP gel in vitro, and the combined use of these two agents can significantly promote repair of the degenerated discs in vivo.

Study Design: Intervertebral disc calcification of T6-T7, T7-T8 discs associated with ossification of posterior longitudinal ligament (OPLL) in a child is reported., Objective: To discuss the natural history and management of calcification of T6-T7, T7-T8 discs with OPLL., Summary of Background Data: Calcified intervertebral discs are rare in children. Cervical disc calcification has already been described. However, thoracic disc calcification associated with OPLL has not been reported., Methods: An 11-year-old boy presented with progressive back pain for 6 months. Neurologic examination showed numbness in both lower extremities. The knee jerk reflex of the patient was hypertonic. The muscle strength of both lower extremities were Grade 4, with reduction. He was treated with a lumbar belt for 2 weeks., Results: Initial thoracic spine radiograph and CT scan showed two adjacent calcified discs of T6-T7, T7-T8 associated with T6-T7 OPLL, resulting in marked spinal canal stenosis. His neurologic symptoms subsided and his back pain disappeared after a 2-week conservative treatment. Three months later CT scan showed that the calcification of T6-T7, T7-T8 discs was aggravated, but the T6-T7 OPLL was relieved., Conclusion: The natural history of intervertebral disc calcification is usually benign. In this case, the improvement of OPLL is associated with the stabilization of the maturely fused calcified disc. Spontaneous resolution of the OPLL and recovery of normal neurologic function can be expected with conservative treatment.

Intervertebral disc degeneration (IDD) is characterized by excessive inflammatory reaction, and neuropeptide Y (NPY) was reported to have anti-inflammatory effect. However, the effect of NPY on NP cells has not been investigated up to date. This study aimed to clarify the role of NPY on the process of IDD. Fourteen fresh human lumbar intervertebral discs were harvested, and degeneration-related proteins were examined. Pfirrmann grading system was used to evaluate IDD. Rat nucleus pulposus (NP) cells were used to investigate the effect of NPY on the proliferation, apoptosis, and extracellular matrix (ECM) in NP cell induced by IL-1βin vitro. The expression levels of NPY and its receptors (type 1 receptor, Y1R, and type 2 receptor, Y2R) were detected via immunohistochemical analysis, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and proliferation were explored using cell counting kit-8 assay, western blot, and immunofluorescence analysis. Cell apoptosis was investigated by Hoechst staining, JC-1 Staining, annexin V-FITC/PI double staining, and western blot. The secretion of NPY from NP cells was determined via enzyme-linked immunosorbent assay (ELISA). The expression of anabolic and catabolic gene was analyzed by qRT-PCR, western blot, immunofluorescence analysis, and ELISA. The expression of Y2R was significantly increased in both human degenerative intervertebral discs and IL-1β-induced NP cells. Although no positive results for NPY indicated by western blot both in vivo and in vitro, ELISA results demonstrated that the secretion of NPY from NP cells was increased by low-concentration IL-1β, but was decreased when the concentration of IL-1β was 30 ng/ml and above. In addition, NPY could promote NP cells proliferation and protect NP cells against IL‑1β‑induced apoptosis via suppressing mitochondrial-mediated apoptosis pathway. What's more, NPY can suppress the expression of catabolic gene and ameliorate IL-1β- induced matrix degeneration in NP cells. In conclusion, NPY could promote NP cell proliferation and alleviate IL‑1β‑induced cell apoptosis via mitochondrial pathway. In addition, NPY can suppress the expression of ECM‑catabolic proteinases and ameliorate IL-1β- induced ECM degeneration in vitro. [ABSTRACT FROM AUTHOR]