Emodin ameliorates matrix degradation and apoptosis in nucleus pulposus cells and attenuates intervertebral disc degeneration through LRP1 in vitro and in vivo.

Low back pain (LBP) is the leading cause of disability worldwide, with a strong correlation to intervertebral disc degeneration (IDD). Inflammation-induced extracellular matrix (ECM) degradation plays a major role in IDD's progression. Emodin, known for its anti-inflammatory effects and ability to inhibit ECM degradation in osteoarthritis, but its role in IDD is unclear. Our study aimed to explore emodin's role and mechanisms on IDD both in vivo and in vitro. We discovered that emodin positively regulated anabolic markers (COL2A1, aggrecan) and negatively impacted catabolic markers (MMP3, MMP13) in nucleus pulposus cells, while also inhibiting cell apoptosis under inflammation environment. We revealed that emodin inhibits inflammation-induced NF-ĸB activation by suppressing the degradation of LRP1 via the proteasome pathway. Additionally, LRP1 was validated as essential to emodin's regulation of ECM metabolism and apoptosis, both in vitro and in vivo. Ultimately, we demonstrated that emodin effectively alleviates IDD in a rat model. Our findings uncover the novel pathway of emodin inhibiting ECM degradation and apoptosis through the inhibition of NF-κB via LRP1, thus alleviating IDD. This study not only broadens our understanding of emodin's role and mechanism in IDD treatment but also guides future therapeutic interventions.

Comprehensive analysis of angiogenesis pattern and related immune landscape for individual treatment in osteosarcoma.

Postoperative recurrence and metastasis are the main reasons for the poor prognosis of osteosarcoma (OS). Currently, an ideal predictor for not only prognosis but also drug sensitivity and immunotherapy responses in OS patients is urgently needed. Angiogenesis plays a crucial role in tumour progression, which suggests its immense potential for predicting prognosis and responses to immunotherapy for OS. Angiogenesis patterns in OS were explored in depth in this study to construct a prognostic model called ANGscore and clarify the underlying mechanism involved in the immune microenvironment. The efficacy and robustness of the model were validated in multiple datasets, including bulk RNA-seq datasets (TARGET-OS, GSE21257), a single-cell RNA-seq dataset (GSE152048) and immunotherapy-related datasets (GSE91061, GSE173839). OS patients with a high ANGscore had a worse prognosis, accompanied by the immune desert phenotype. Pseudotime and cellular communication analyses in scRNA-seq data revealed that as the ANGscore increased, the malignant degree of cells increased, and IFN-γ signalling was involved in tumour progression and regulation of the tumour immune microenvironment. Furthermore, the ANGscore was associated with immune cell infiltration and the response rate to immunotherapy. OS patients with high ANGscore might be resistant to uprosertib, and be sensitive to VE821, AZD6738 and BMS.345541. In conclusion, we established a novel ANGscore system by comprehensively analysing the expression pattern of angiogenesis genes, which can accurately differentiate the prognosis and immune characteristics of OS populations. Additionally, the ANGscore can be used for patient stratification during immunotherapy, and guide individualized treatment strategies.

TAK-715 alleviated IL-1ß-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo.

BACKGROUND: Intervertebral disc degeneration (IDD) is one of the most common disorders related to the spine. Inflammation, apoptosis and extracellular matrix (ECM) degradation contribute to disc degeneration in nucleus pulposus cells (NPCs). This study focused on the role and mechanism of the p38 inhibitor TAK-715 in intervertebral disc degeneration. METHODS: NPCs were treated with IL-1ß to mimic apoptosis, followed by the addition of TAK-715. It was determined that apoptosis, inflammatory mediators (COX-2), inflammatory cytokines (HMGB1), and ECM components (collagen II, MMP9, ADAMTS5, and MMP3) existed in NPCs. In addition, the p38MAPK signaling pathways were examined. The role of TAK-715 in vivo was determined by acupuncture-induced intervertebral disc degeneration. Following an intradiscal injection of TAK-715, MRI and a histopathological analysis were conducted to assess the degree of degeneration. RESULTS: IL-1ß-induced apoptosis was alleviated by TAK-715 in vitro, and antiapoptotic proteins were upregulated. Furthermore, TAK-715 blocked IL-1ß-induced inflammatory mediator production (COX-2) and inflammatory cytokine production (HMGB1) and degraded the ECM (collagen II, MMP9, ADAMTS5, and MMP3). By inhibiting the phosphorylation of p38, TAK-715 exerted its effects. In a rat tail model, TAK-715 ameliorates puncture-induced disc degeneration based on MRI and histopathology evaluations. CONCLUSION: TAK-715 attenuated intervertebral disc degeneration in vitro and in vivo, suggesting that it might be an effective treatment for IDD.

Correlation between posterior paraspinal muscle atrophy and lumbar intervertebral disc degeneration in patients with chronic low back pain.

BACKGROUND: Although enormous studies have been devoted to solving the problem of intervertebral disc degeneration/herniation, little attention is paid to the effect of paraspinal muscles on it. We aimed to investigate the correlation between paraspinal muscle atrophy and lumbar disc degeneration to recognize paraspinal muscle atrophy and its importance to the spine. PATIENTS AND METHODS: A total of 107 patients were enrolled in the study (65 females, 42 males; age 50.87 ± 15.391 years old). Cross-sectional area, functional cross-sectional area, and fatty infiltration of the posterior paraspinal muscles were measured at the level of L4/5, and the degree of facet joint degeneration was evaluated at the levels of L3/4, L4/5, and L5/S1 by MRI. After controlling the confounding factors by multiple linear regression, the correlations among paraspinal muscle atrophy, disc degeneration, and facet joint degeneration were analyzed. Meanwhile, Pearson/Spearson rank analysis was used to analyze the correlation between clinical symptoms (VAS and ODI) and paraspinal muscle atrophy. RESULTS: There was a strong correlation between paraspinal muscle atrophy and disc degeneration after controlling the confounding factors (p < 0.05, R > 0.5). There was a weak correlation between paraspinal muscle atrophy and facet joint degeneration (p < 0.05, R < 0.5). There was a significant correlation between facet joint degeneration and intervertebral disc degeneration (p < 0.05, R > 0.7). The fatty infiltration of paraspinal muscle was weakly correlated with ODI (p < 0.05, R < 0.3), but VAS was not. CONCLUSIONS: The degree of paraspinal muscle atrophy increased with lumbar disc degeneration and facet joint degeneration and fatty infiltration of multifidus was more susceptible to weight.

AOSRV: Development and preliminary performance assessment of a new robotic system for autonomous percutaneous vertebroplasty.

BACKGROUND: Percutaneous vertebroplasty (PVP) is one of the most effective treatments for patients with vertebral fracture that need surgical treatment, and surgical robotics are promising tools to provide surgeons with improved precision, surgical efficiency and reduce radiation exposure. However, there are currently few robotics that are developed to help assist with PVP. METHODS: A new spinal surgical robotic system 'AOSRV' for autonomous vertebral puncture and bone cement injection was designed and customised in this study. To investigate its practical abilities and the advantages, we performed single-segment/double-segment PVP simulation surgeries on pig spinal specimens manually and using AOSRV. RESULTS: By contrast with the freehand group (FG) in single-segment (SS)/double-segment (DS) surgery, the robotic group (RG) was superior in the operation time (RGSS = 21.14 ± 4.11 min, FGSS = 33.17 ± 6.83 min; RGDS = 42.39 ± 7.31 min, FGDS = 62.86 ± 20.39 min), puncture adjustments (RGSS = 2.30 ± 1.77, FGSS = 14.86 ± 5.46; RGDS = 3.91 ± 1.76, FGDS = 20.00 ± 7.76), intraoperative fluoroscopies (RGSS = 4.10 ± 1.52, FGSS = 20.57 ± 5.44; RGDS = 7.82 ± 1.40, FGDS = 25.91 ± 7.23) and bone cement leakage rate (RGSS = 30%, FGSS = 71.4%; RGDS = 38.6%, FGDS = 83.3%). CONCLUSIONS: AOSRV was successfully developed and had a promising preliminary performance. An innovative attempt was made for the blank space of the autonomous vertebroplasty surgical robotics, and it may shed a light on more promising applications in the future.

Glomus tumor of uncertain malignant potential within the cervical spine: a case report.

The case report details the first glomus tumor (GT) of uncertain malignant potential within the cervical spine. The patient had been experiencing neck pain and numbness of the left side of her body for 3 months. Magnetic resonance imaging (MRI) revealed a lesion with the dimensions 22 mm × 11 mm in the left side of the intervertebral foramen and epidural of C1-5. When the patient appeared aggravating symptoms, we performed an emergency surgery to relieve the spinal cord compression resulting from the growing tumor. During the surgery, a grey-brown friable tumor was observed, and the tumor was located both outside and inside of the cervical spine. Morphological and immunohistochemical (IHC) analysis showed that the lesion was a globular tumor with uncertain malignant potential. After the surgery, the patient received adjuvant radiotherapy consisting of 58.9 Gy in 23 fractions postoperatively. The MRI at 4 months after the surgery showed a progression of the tumor, at which point the patient ceased treatment. GT of uncertain malignant potential within the cervical spine lacks specific clinical manifestations and reliable non-invasive means of examination, so its diagnosis depends on pathological biopsy and IHC examination. Surgical excision is the first treatment to relieve the symptoms of nerve compression. Further research of postoperative radiotherapy and chemotherapy is required to improve treatment options.

Prediction of a Potential Mechanism of Intervertebral Disc Degeneration Based on a Novel Competitive Endogenous RNA Network.

Low back pain which resulted from intervertebral disc degeneration (IDD) is a common health problem that afflicts people all over the world. Due to the lack of an overall understanding of the molecular interactions involved in IDD, we hope to better understand the pathogenetic mechanisms that drive the degenerative process. The purpose of this study is to obtain mRNAs, miRNAs, lncRNAs, and circRNAs associated with IDD gained from public databases and to establish an interaction network. According to the results of microarray analysis and bioinformatics analysis from the contrast of IDD and normal nucleus pulposus tissues, a total of 49 mRNAs, 10 miRNAs, 30 lncRNAs, and 4 circRNAs were obtained and a lncRNA/circRNA-miRNA-mRNA interaction network was constructed. NEAT1-miR-5100-COL10A1 and miR663AHG/HEIH/hsa-circ-0003600-miR-4741-HAS2/HYAL1/LYVE1 might be potential interaction axes of the molecular mechanism in IDD. The increased expression of NEAT1 might inhibit miR-5100 and subsequently upregulate the expression of COL10A1, which leads to IDD, while the increased expression of miR663AHG/HEIH/hsa-circ-0003600 might inhibit miR-4741 and indirectly upregulate HAS2/HYAL1/LYVE1, and leads to the protection from IDD. More interaction axes are to be exploited to provide theoretical bases for further study on IDD.