Extracellular vesicles (EVs), defined as cell-secreted nanoscale vesicles that carry bioactive molecules, have emerged as a promising therapeutic strategy in tumor and tissue regeneration. Their potential in repairing intervertebral disc degeneration (IDD) through multidimensional regulatory mechanisms is a rapidly advancing field of research. This paper provided an overview of the mechanisms of EVs in IDD repair, thoroughly reviewed recent literature on EVs for IDD, domestically and internationally, and summarized their therapeutic mechanisms. In IDD repair, EVs could act through different mechanisms at the molecular, cellular, and tissue levels. At the molecular level, EVs could treat IDD by inhibiting inflammatory reactions, suppressing oxidative stress, and regulating the synthesis and decomposition of extracellular matrix. At the cellular level, EVs could treat IDD by inhibiting cellular pyroptosis, ferroptosis, and apoptosis and promoting cell proliferation and differentiation. At the tissue level, EVs could treat IDD by inhibiting neovascularization. EVs have a strong potential for clinical application in the treatment of IDD and deserve more profound study.
Extracellular Vesicles/physiology* ; Humans ; Intervertebral Disc Degeneration/therapy* ; Apoptosis ; Cell Proliferation ; Oxidative Stress ; Cell Differentiation ; Extracellular Matrix/metabolism* ; Animals ; Pyroptosis

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

OBJECTIVE: To summarize recent research progress in hydrogel-based growth factors for treatment of intervertebral disc degeneration (IDD). METHODS: The relevant literature on hydrogel-based growth factors for IDD treatment at home and abroad was extensively reviewed, and their advantages and therapeutic effects in repairing IDD were analyzed and summarized. RESULTS: Hydrogels exhibit high hydration, biocompatibility, and biodegradability, enabling targeted delivery and sustained release of growth factors such as growth differentiation factors and transforming growth factors. This facilitates enhanced efficacy in promoting cell proliferation, extracellular matrix synthesis, and reducing inflammatory responses. Consequently, hydrogels demonstrate broad application prospects in the repair of IDD. CONCLUSION Research on hydrogel-based growth factors for treating IDD demonstrates advantages such as avoiding disc damage caused by repeated injections and controlling growth factor release concentrations. However, drawbacks include the limited variety of loaded growth factors and the need to verify the long-term stability and biocompatibility of hydrogels. Therefore, further research is required on aspects such as the types of loaded growth factors and the long-term stability and biocompatibility of hydrogels to establish an experimental foundation for their clinical application.
Intervertebral Disc Degeneration/therapy* ; Hydrogels/chemistry* ; Humans ; Intercellular Signaling Peptides and Proteins/administration & dosage* ; Biocompatible Materials/chemistry* ; Animals ; Tissue Engineering/methods* ; Cell Proliferation/drug effects* ; Drug Delivery Systems

OBJECTIVE: To explore mechanisms of acid-sensing ion channel 1 (ASIC1) mediated lumbar nucleus pulposus cell apoptosis through extracellular-signalregulated protein kinase 5 (ERK5) signaling pathway and mitochondrial dysfunction pathway. METHODS: Totally 34 patients with degenerative lumbar disc herniation (LDH) admitted from January 2020 to December 2022 were collected as research objects, including 21 males and 13 females;aged from 29 to 52 years old with an average of (37.43±4.75) years old;22 patients with grade Ⅱ and 12 patients with grade Ⅳ, according to Pfirrmann grading criteria;15 patients with L_4,5 and 19 patients with L₅S₁. The expression of ASIC1 in nucleus pulposus of LDH patients was measured by immunohistochemical staining. Nucleus pulposus cells were cultured by primary culture method, identified by toluidine blue staining and immunohistochemical staining, and the expression of ASIC1 protein was located by immunofluorescence staining. According to the addition of siRNA-ASIC1, ASIC1 overexpression plasmid, and ERK5 inhibitors, the nucleus pulpocyte was divided into three groups, named as SIRNA-silenced group, overexpression group, and inhibitor group, with 3 patients in each group. Cells of each group were collected at 72 h after intervention, expression of ASIC1, ERK5, BCL-xL/BCL-2-associated Death promoter (Bad), B-cell lymphoma-2 associated X (Bax) and B-cell lymphoblast-2 gene (Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR);intracellular calcium ion levels were detected by calcium ion kit, mitochondrial membrane potential was detected by JC-1 kit, and apoptosis was observed by AV-PI kit. RESULTS: In LDH patients with grade Ⅳ, nucleus pulposus tissue removed during operation revealed poor elasticity, white color and poor ductility, and immunohistochemical results showed increased ASIC1 expression. There was no significant difference in mRNA relative expression of ASIC1 between siRNA silencing group (0.31±0.03) and inhibitor group (0.39±0.05) (P>0.05). The mRNA relative expression level of ERK5 in siRNA silencing group(0.32±0.05) was significantly higher than that in inhibitor group (0.15±0.04)(P<0.05), which suggested ERK5 was the downstream molecule of ASIC1. The mRNA relative expression levels of apoptosis promoting factor Bad and Bax in siRNA silencing group and inhibitor group were lower than those in overexpression group(P<0.05), the relative expression level of anti-apoptosis factor Bcl-2 mRNA was significantly increased (P<0.05). The calcium content in overexpression group was higher than that in siRNA silencing and inhibitor groups (P<0.05), the normal proportion of mitochondrial membrane potential in overexpression group was lower than that in siRNA silencing and inhibitor group (P<0.05), and the apoptosis rate in overexpression group was higher than that in siRNA silencing and inhibitor group (P<0.05). CONCLUSION After the activation of ASIC1 channel protein, calcium ions could enter the cells and act as a second messenger molecule to regulate apoptosis of nucleus pulposus cells by ERK5 signaling pathway and mitochondrial disorder pathway.
Humans ; Acid Sensing Ion Channels/physiology* ; Male ; Female ; Apoptosis ; Middle Aged ; Adult ; Signal Transduction ; Mitogen-Activated Protein Kinase 7/physiology* ; Mitochondrial Diseases/genetics* ; Nucleus Pulposus/metabolism* ; Intervertebral Disc Degeneration/metabolism* ; Mitochondria/metabolism* ; Intervertebral Disc Displacement/genetics*

OBJECTIVE: To explore the potential causal relationship between intervertebral disc degeneration and certain autoimmune diseases. METHODS: Genome-wide association study (GWAS) data of 5 autoimmune diseases were obtained from large-scale GWAS databases. Data on internal vertebral disc degeneration (IVDD) were derived from the FinnGen consortium, which included 294, 770 controls and 41, 669 cases. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to investigate the potential causal relationship between the 5 autoimmune diseases and IVDD. Multiple analytical methods were adopted, including MR methods such as inverse variance weighting(IVW), MR-Egger, weighted median, weighted mode, and simple mode. Cochran's Q test, leave-one-out analysis, and MR-Egger intercept test were conducted to assess heterogeneity, robustness, and pleiotropy. For the robustness of the results, MR-PRESSO was used to detect outliers, and MR analysis was re-conducted after removing the outliers. RESULTS: The MR analysis results showed that there might be a bidirectional causal relationship between ankylosing spondylitis(AS) and IVDD:AS on IVDD, OR=1.038, 95%CI (1.024, 1.053), P=0.000;and IVDD on AS, OR=2.117, 95%CI(1.065, 4.207), P=0.032. There might be a positive correlation between IVDD and rheumatoid arthritis(RA) as well as systemic lupus erythematosus(SLE):IVDD on RA, OR=1.184, 95%CI(1.071, 1.309), P=0.001;and IVDD on SLE, OR=1.678, 95%CI(1.187, 2.372), P=0.003. There was no significant correlation between ulcerative colitis(UC), autoimmune thyroiditis(ATD) and IVDD. After removing outliers by MR-PRESSO and re-conducting MR analysis, the results did not change qualitatively. Sensitivity analysis indicated that the results were robust to potential sources of bias. CONCLUSION AS and IVDD may be risk factors for each other, and IVDD may be a potential risk factor for RA and SLE. These findings provide a basis for guiding the prevention and combined diagnosis and treatment of IVDD, AS, RA, and SLE, while the specific underlying mechanisms still require further experimental basic research.
Humans ; Intervertebral Disc Degeneration/etiology* ; Mendelian Randomization Analysis ; Autoimmune Diseases/complications* ; Genome-Wide Association Study ; Spondylitis, Ankylosing/genetics* ; Arthritis, Rheumatoid/genetics*

OBJECTIVE: To investigate the early clinical efficacy, safety, and application value of one-hole split endoscopy (OSE)-assisted transforaminal lumbar interbody fusion(TLIF) in the treatment of lumbar degenerative diseases. METHODS: A retrospective analysis was conducted on 17 patients with lumbar degenerative diseases who underwent OSE-assisted TLIF between June 2023 and June 2024. There were 10 males and 7 females, with a mean of (55.30±6.52) years old ranging 43 to 65 years. The disease duration ranged from 3 to 36 months with a mean of(12.4±13.3) months. The disease distribution was as follows:lumbar disc herniation (7 cases), lumbar spinal stenosis (5 cases), and lumbar spondylolisthesis (2 cases). Operative time, incision length, intraoperative blood loss, number of intraoperative fluoroscopic exposures, time to ambulation, postoperative hospital stay, and complications were recorded. The dural sac area at the affected segment, visual analogue scale (VAS) for low back pain and leg pain, and Oswestry disability index (ODI) were recorded preoperatively and postoperatively. The modified MacNab criteria were used to evaluate the surgical outcome at the final follow-up. RESULTS: All 17 patients successfully underwent surgery and were followed up for 3 to 15 months with a mean of (8.4±3.3) months. The operative time was 120 to 200 minutes with a mean of (143.2±22.0) minutes, the incision length on the decompression side was 1.80 to 4.00 cm with a mean of (2.56±0.65) cm, intraoperative blood loss was 50 to 300 ml with a mean of (161.2±72.5) ml, the number of fluoroscopic exposures was 15 to 38 with a mean of (23.4±6.5), time to ambulation was 24 to 72 hours with a mean of (49.2±11.9) hours, and postoperative hospital stay was 3 to 9 days with a mean of (4.9±1.5) days. Two patients developed transient lower limb pain and numbness, which completely resolved with conservative treatment. The postoperative dural sac area was (121.47±14.90) mm², which was significantly larger than the preoperative area (51.47±7.69) mm²(P<0.001). The VAS for low back pain were (6.23±1.64), (2.94±1.43), and (1.94±0.75) at preoperation, 3 days postoperation, and final follow-up, respectively;the VAS for leg pain were (7.06±1.43), (2.35±1.17), and (2.06±0.90) at the same time points. The VAS at all postoperative time points were significantly lower than preoperative scores (P<0.001). The ODI at final follow-up was (25.29±8.15)%, which was significantly better than the preoperative ODI of(82.35±5.16)%(P<0.001). At the final follow-up, the MacNab surgical outcome was excellent in 11 cases, good in 4 cases, and fair in 2 cases. CONCLUSION OSE-assisted TLIF is an effective, safe, and minimally invasive technique with a gentle learning curve for the treatment of lumbar degenerative diseases, capable of effectively relieving symptoms and improving function.
Humans ; Male ; Female ; Middle Aged ; Lumbar Vertebrae/surgery* ; Adult ; Aged ; Spinal Fusion/methods* ; Retrospective Studies ; Endoscopy/methods* ; Intervertebral Disc Degeneration/surgery* ; Spondylolisthesis/surgery* ; Treatment Outcome

OBJECTIVE: To investigate the clinical value of MRI modified water-lipid separation technique (mDIXON-Quant) in terms of T2* values and fat fraction (FF) values for evaluating the degree of cervical intervertebral disc degeneration. METHODS: A total of 118 patients who underwent routine MRI of the cervical vertebra and the mDIXON-Quant examination in Fuyang People's Hospital from March 2019 to January 2024 were collected. The T2* values of C2/3 to C6/7 intervertebral discs and FF values of the upper and lower vertebral bodies were measured. Cervical intervertebral disc degeneration was graded according to the Pfirrmann criteria. The T2* values and FF values of different patients were compared with the Pfirrmann grades, and the correlation between T2* values, FF values, and Pfirrmann grades was analyzed by Spearman correlation. RESULTS: The T2* values of cervical intervertebral discs in grades I, II, III, IV, and V all showed a decreasing trend ( P＜0.05). The decreasing order of FF values in the upper cervical vertebra was IV, V, III, II, and I ( F=93.28, P＜0.05), and the decreasing order of FF values in the lower cervical vertebra was IV, III, V, II, and I ( F=112.037, P＜0.05). Spearman correlation analysis showed that the T2* values of cervical intervertebral discs were negatively correlated with the Pfirrmann grades ( P＜0.05), and the FF values of the upper and lower vertebrae were positively correlated with the Pfirrmann grades ( P＜0.05). CONCLUSION The mDIXON-Quant technique can be used to quantify the T2* values and FF values of cervical intervertebral disc degeneration and plays an important role in accurate clinical diagnosis and evaluation of treatment effects.
Humans ; Intervertebral Disc Degeneration/diagnostic imaging* ; Cervical Vertebrae/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Adult ; Intervertebral Disc/diagnostic imaging* ; Lipids

Intervertebral disc degeneration (IDD) is the main cause of low back pain. Immune cells play an extremely important role in regulating the progression of IDD by interacting with nucleus pulposus (NP) cells and the extracellular matrix (ECM). Healthy NP tissue is a vascular-free and immune-privileged tissue that does not normally interact with macrophages. However, the establishment of neovascularization channels in damaged intervertebral discs has led to extensive cross-talk between NP and macrophages, with different results depending on microenvironmental stimuli. Based on this, this review reviewed the correlation between IDD and low back pain, summarized the source and function of macrophages, and discussed the possible regulatory mechanism between macrophages and discogenic pain. Finally, potential therapies targeting macrophages to delay IDD in recent years were also discussed, aiming to emphasize the important role of immunology in IDD and provide a new direction for the prevention and treatment of IDD.
Humans ; Intervertebral Disc Degeneration/complications* ; Macrophages/immunology* ; Low Back Pain/immunology* ; Nucleus Pulposus ; Animals ; Extracellular Matrix

OBJECTIVE: To compare the effectiveness of robot-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open freehand TLIF for the treatment of single-level degenerative lumbar spondylolisthesis (DSL) and analyse the influence on postoperative adjacent segmental degeneration (ASD). METHODS: The clinical data of 116 patients with L _4、5 DLS who were admitted between November 2019 and October 2021 and met the selection criteria were retrospectively analyzed. According to the surgical methods, they were divided into the robotic group (45 cases, who underwent robot-assisted MIS-TLIF) and the open group (71 cases, who underwent open freehand TLIF). There was no significant difference in baseline data such as gender, age, body mass index, DLS Meyerding grading, and preoperative Pfirrmann grading, Weishaupt grading, L _{3, 4} intervertebral disc height (DH), L _{3, 4} intervertebral mobility, sagittal parameters [including pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT)], and Cage height ( P>0.05). The grade of facet joint violation (FJV) by pedicle screws on the superior articular process was assessed postoperatively. Sagittal parameters, L _{3, 4} DH, L _{3, 4} DH loss, and L _{3, 4} intervertebral mobility were measured preoperatively and at last follow-up in order to determine whether ASD occurred. Based on the occurrence of postoperative ASD, logistic regression analysis was used to identify the risk factors for ASD after TLIF. RESULTS: Patients in both groups were followed up 21-47 months, with a mean of 36.1 months; there was no significant difference in the follow-up time between the two groups ( P>0.05). The occurrence of postoperative FJV was significantly better in the robotic group than in the open group ( P<0.05). At last follow-up, the difference in the change values of sagittal parameters PI, PT, SS, and LL was not significant when comparing the two groups of patients ( P>0.05); the change values of L _{3, 4} DH and L _{3, 4} DH loss in the robotic group were smaller than those in the open group, and the change value of L _{3, 4} intervertebral mobility was larger than that in the open group, and the differences were significant ( P<0.05). At last follow-up, ASD occurred in 8 patients (17.8%) in the robotic group and 35 patients (49.3%) in the open group, and the difference in ASD incidence between the two groups was significant ( P<0.05). logistic regression analysis showed that open surgery, preoperative Pfirrmann grading Ⅳ-Ⅴ, preoperative Weishaupt grading ≥2, and postoperative FJV grading ≥1 were risk factors for the development of ASD after TLIF ( P<0.05). CONCLUSION Compared with traditional open surgery, orthopedic robot-assisted MIS-TLIF in the treatment of single-level DLS can more accurately insert pedicle screws, reduce the loss of DH and the occurrence of FJV, and effectively reduce the incidence of mid-postoperative ASD. Preoperative disc and synovial joint degeneration in adjacent segments, nonrobotic-assisted minimally invasive therapy, and FJV are risk factors for ASD after TLIF.
Humans ; Spinal Fusion/methods* ; Spondylolisthesis/surgery* ; Lumbar Vertebrae/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Robotic Surgical Procedures/methods* ; Male ; Treatment Outcome ; Female ; Intervertebral Disc Degeneration/surgery* ; Retrospective Studies ; Postoperative Complications/etiology* ; Risk Factors ; Middle Aged

OBJECTIVE: To observe the early clinical efficacy of the zero-remember cervical Solis fusion device in the treatment of adjacent segment degeneration(ASD) revision after anterior cervical discectomy and fusion(ACDF). METHODS: A retrospective analysis was performed for 13 patients with adjacent spondylosis after anterior cervical discectomy bone graft fusion with Solis fusion device, including 5 males and 8 females, aging from 56 to 78 years old. The patients had intractable neck pain or superficial paresthesia of upper extremities before operation, and the effect of conservative treatment was not good. The operation time, intraoperative blood loss and postoperative complications were recorded. Before operation, 1 week postoperative and final follow-up, the visual analogue scale(VAS) and Japanese Orthopaedic Association(JOA) scores were used to assess clinical efficacy. X-ray and CT of the cervical spine were performed to measure and evaluate the height of the intervertebral space and intervertebral fusion. RESULTS: All patients were followed up from 18 to 36 months. All 13 patients successfully completed revision surgery with single gaps. The operation time was 63 to 93 min, the intraoperative blood loss was 15 to 83 ml. The pain VAS was reduced from 4 to 7 points before surgery to 1 to 3 points at 1 week and 1 to 2 points at the final follow-up. The height of the intervertebral space was increased from 5.2 to 7.2 mm before surgery to 6.4 to 8.0 mm at 1 week after surgery and 6.4 to 7.9 mm at the final follow-up. The JOA score was increased from 11 to 17 points before surgery to 13 to 17 points at 1 week after surgery and 16 to 17 points at the final follow-up visit. At the final follow-up, AP and lateral X-ray films of cervical spine showed homogeneous bone fusion of the Solis fusion. One patient developed transient left upper limb weakness after surgery, which recovered at follow-up, and all patients had no dysphagia, incision hematoma or infection, and displacement. CONCLUSION The early clinical efficacy of Solis fusion device in the treatment of orthospondylosis after anterior cervical intervertebral fusion is satisfactory, and it has the advantages of less surgical trauma, adequate decompression, high osseointegration rate and fewer complications, which can provide a new option for minimally invasive treatment of orthospondylosis after cervical spine surgery.
Humans ; Male ; Female ; Middle Aged ; Spinal Fusion/methods* ; Aged ; Diskectomy/methods* ; Cervical Vertebrae/surgery* ; Retrospective Studies ; Bone Transplantation/methods* ; Intervertebral Disc Degeneration/surgery* ; Reoperation