Significant overlap of inflammatory and degenerative features on imaging among patients with degenerative disc disease, diffuse idiopathic skeletal hyperostosis and axial spondyloarthritis: a real-life cohort study.

BACKGROUND: Differentiating between degenerative disc disease (DDD), diffuse idiopathic skeletal hyperostosis (DISH), and axial spondyloarthritis (axSpA) represents a diagnostic challenge in patients with low back pain (LBP). We aimed to evaluate the distribution of inflammatory and degenerative imaging features in a real-life cohort of LBP patients referred to a tertiary university rheumatology center. METHODS: In a retrospective cross-sectional analysis of patients referred for LBP, demographics, symptom information, and available imaging were collected. SpA-like changes were considered in the spine in the presence of one of the following lesions typically related to SpA: erosions, sclerosis, squaring, and syndesmophytes on conventional radiographs (CR) and bone marrow oedema (BMO), erosions, sclerosis, and fat lesions (FL) on MRI. SIJ CR were graded per New York criteria; on MRIs, SIJs were evaluated by quadrant for BMO, erosions, FL, sclerosis and ankylosis, similar to the approach used by the Berlin SIJ MRI scoring system. The final diagnosis made by the rheumatologist was the gold standard. Data were presented descriptively, by patient and by quadrant, and compared among the three diagnosis groups. RESULTS: Among 136 referred patients, 71 had DDD, 38 DISH, and 27 axSpA; median age 62 years [IQR55-73], 63% males. On CR, SpA-like changes were significantly higher in axSpA in the lumbar (50%, vs. DDD 23%, DISH 22%), in DISH in the thoracic (28%, vs. DDD 8%, axSpA 12%), and in DDD in the cervical spine (67% vs. DISH 0%, axSpA 33%). On MRI, BMO was significantly higher in DISH in the thoracic (37%, vs. DDD 22%, axSpA 5%) and equally distributed in the lumbar spine (35-42%). FL were significantly more frequently identified in DISH and axSpA in the thoracic (56% and 52%) and DDD and axSpA in the lumbar spine (65% and 74%, respectively). Degenerative changes were frequent in the three groups. Sacroiliitis (NY criteria) was identified in 49% (axSpA 76%, DDD 48%, DISH 29%). CONCLUSION: A significant overlap was found among DDD, DISH, and axSpA for inflammatory and degenerative imaging features. Particularly, SpA-like spine CR features were found in one-fourth of patients with DISH, and MRI BMO was found in one-third of those patients.

Melatonin: Evolving Physiological Understanding and Potential Therapeutic Role in Pain Medicine Including Intervertebral Disc Degeneration.

BACKGROUND: Melatonin, one of the most versatile hormones in the body, is well appreciated in managing circadian rhythm and for antioxidant properties. Produced in the pineal gland and within mitochondria, melatonin influences many physiologic processes through receptor mediated and direct effects. OBJECTIVE: The present investigation explores the evolving pharmacologic properties of melatonin, as well as current therapeutic uses in areas where mitigating oxidative stress, inflammation, and cellular senescence. This review also delves into novel therapeutic potential of melatonin and how current research is revealing a wide array of therapeutic promise in pain medicine. STUDY DESIGN: A systematic review of randomized controlled trials (RCTs) and observational studies was performed using various search engines focused on melatonin and its role in pain medicine. METHODS: The available literature on melatonin and pain medicine was reviewed. A comprehensive literature search of multiple databases from 1966 to July 2024, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included studies and best evidence synthesis were incorporated into qualitative and quantitative evidence synthesis. OUTCOME MEASURES: The primary outcome measure was the proportion of patients receiving melatonin with significant relief and functional improvement of greater than 50% of at least 3 months. Duration of relief was categorized as short-term (less than 6 months) and long-term (greater than 6 months). RESULTS: Melatonin can affect intervertebral disc (IVD) health through the enhancement of survival and function of nucleus pulposus cells, primarily through activation of the ERK1/2 signaling pathway. Melatonin also influences the biochemical environment of the IVD by modulating inflammation and oxidative stress, crucial factors in the pathogenesis of disc degeneration. Melatonin has been shown to reduce senescence and promote autophagy within disc cells, vital for clearing out damaged cellular components, preserving cellular function and preventing deterioration associated with aging and degenerative diseases. LIMITATIONS: Despite the availability of multiple studies, the paucity of clinical pain related literature is considered as the major drawback. CONCLUSION: Based on the present systematic review, melatonin plays a critical role in sleep, but evolving studies have demonstrated substantive roles in mitigating degenerative conditions in various tissues, including IVD degeneration. Ongoing studies will better clarify the role of melatonin as a potential therapeutic agent, including the targeted delivery to various body regions.

Percutaneous nucleoplasty and intradiscal electrothermal therapy in the management of lumbar discogenic pain: A retrospective comparative study.

Percutaneous lumbar nucleoplasty (PLN) and intradiscal electrothermal therapy (IDET) are effective treatment options for discogenic low back pain (D-LBP). We evaluated the effectiveness of PLN and IDET and the positive predictive factors associated with intradiscal procedures. We reviewed the medical records of 205 patients who underwent IDET or PLN in patients with D-LBP followed by positive provocation discography. A successful outcome was defined as ≥ 50% pain relief on the numerical rating scale (NRS) pain score at the 6-month follow-up visit. The relationship between the outcome of the intradiscal procedure and clinical variables was investigated using multivariate analyses. Of the 142 patients (89 with PLN and 53 with IDET), 86 (60.5%) experienced a successful outcome, which was more substantial in PLN (n = 61, 68.5%) than in IDET (n = 25, 47.2%; P = .010). The high-grade Modified Dallas Discogram Scale in provocation discography and a procedure at the L3/L4 spinal level were independent positive predictors of successful outcomes (P = .023 and .010, respectively). Coexisting psychiatric disorders, such as depression and anxiety, were negative predictors of successful treatment (P = .007). No serious complications related to the intradiscal procedures were reported during the 6-month follow-up period. PLN and IDET might be effective for managing low back pain (LBP) from internal disc disruption (IDD). The high-grade Modified Dallas Discogram, a procedure at the L3/4 spinal level, and the absence of neuropsychiatric disorders could be positive factors for the successful outcome of the intradiscal procedure.

Efficacy and safety of navigation robot-assisted versus conventional oblique lateral lumbar interbody fusion with internal fixation in the treatment of lumbar degenerative diseases: A retrospective study.

Effective internal fixation with pedicle screw is a key factor in the success of lumbar fusion with internal fixation. Whether navigation robots can improve the efficacy and safety of screw placement is controversial. Thirty-eight patients who underwent oblique lateral lumbar interbody fusion internal fixation from March 2022 to May 2023 were retrospectively analyzed, 16 cases in the navigational robot group and 22 cases in the fluoroscopy group. Using visual analog score (VAS) for the low back and lower limbs, Oswestry Disability Index to compare the clinical efficacy of the 2 groups; using perioperative indexes such as the duration of surgery, intraoperative blood loss, intraoperative fluoroscopy times, and postoperative hospital stay to compare the safety of the 2 groups; and using accuracy of pedicle screws (APS) and the facet joint violation (FJV) to compare the accuracy of the 2 groups. Postoperative follow-up at least 6 months, there was no statistically significant difference between the 2 groups in the baseline data (P > .05). The navigational robot group's VAS-back was significantly lower than the fluoroscopy group at 3 days postoperatively (P < .05). However, the differences between the 2 groups in VAS-back at 3 and 6 months postoperatively, and in VAS-leg and Oswestry Disability Index at 3 days, 3 months, and 6 months postoperatively were not significant (P > .05). Although duration of surgery in the navigational robot group was significantly longer than in the fluoroscopy group (P > .05), the intraoperative blood loss and the intraoperative fluoroscopy times were significantly lower than in the fluoroscopy group (P < .05). The difference in the PHS between the 2 groups was not significant (P > .05). The APS in the navigation robot group was significantly higher than in the fluoroscopy group, and the rate of FJV was significantly lower than in the fluoroscopy group (P < .05). Compared with the traditional fluoroscopic technique, navigation robot-assisted lumbar interbody fusion with internal fixation provides less postoperative low back pain in the short term, with less trauma, less bleeding, and lower radiation exposure, as well as better APS and lower FJV, resulting in better clinical efficacy and safety.

Causal effects of skin microbiota on intervertebral disk degeneration, low back pain and sciatica: a two-sample Mendelian randomization study.

OBJECTIVE: The purpose of this study is to use two-sample Mendelian randomization (MR) to investigate the causal relationship between skin microbiota, especially Propionibacterium acnes, and intervertebral disc degeneration (IVDD), low back pain (LBP) and sciatica. METHODS: We conducted a two-sample MR using the aggregated data from the whole genome-wide association studies (GWAS). 150 skin microbiota were derived from the GWAS catalog and IVDD, LBP and sciatica were obtained from the IEU Open GWAS project. Inverse-variance weighted (IVW) was the primary research method, with MR-Egger and Weighted median as supplementary methods. Perform sensitivity analysis and reverse MR analysis on all MR results and use multivariate MR to adjust for confounding factors. RESULTS: MR revealed five skin microbiota associated with IVDD, four associated with LBP, and two with sciatica. Specifically, P.acnes in sebaceous skin environments were associated with reduced risk of IVDD; IVDD was found to increase the abundance of P.acnes in moist skin. Furthermore, ASV010 [Staphylococcus (unc.)] from dry skin was a risk factor for LBP and sciatica; ASV045 [Acinetobacter (unc.)] from dry skin and Genus Rothia from dry skin exhibited potential protective effects against LBP; ASV065 [Finegoldia (unc.)] from dry skin was a protective factor for IVDD and LBP. ASV054 [Enhydrobacter (unc.)] from moist skin, Genus Bacteroides from dry skin and Genus Kocuria from dry skin were identified as being associated with an increased risk of IVDD. Genus Streptococcus from moist skin was considered to be associated with an increased risk of sciatica. CONCLUSIONS: This study identified a potential causal relationship between skin microbiota and IVDD, LBP, and sciatica. No evidence suggests skin-derived P.acnes is a risk factor for IVDD, LBP and sciatica. At the same time, IVDD can potentially cause an increase in P.acnes abundance, which supports the contamination theory.

CT-based surrogate parameters for MRI-based disc height and endplate degeneration in the lumbar spine.

PURPOSE: This study investigated potential use of computed tomography (CT)-based parameters in the lumbar spine as a surrogate for magnetic resonance imaging (MRI)-based findings. METHODS: In this retrospective study, all individuals, who had a lumbar spine CT scan and MRI between 2006 and 2012 were reviewed (n = 198). Disc height (DH) and endplate degeneration (ED) were evaluated between Th12/L1-L5/S1. Statistics consisted of Spearman correlation and univariate/multivariable regression (adjusting for age and gender). RESULTS: The mean CT-DH increased kranio-caudally (8.04 millimeters (mm) at T12/L1, 9.17 mm at L1/2, 10.59 mm at L2/3, 11.34 mm at L3/4, 11.42 mm at L4/5 and 10.47 mm at L5/S1). MRI-ED was observed in 58 (29%) individuals. CT-DH and MRI-DH had strong to very strong correlations (rho 0.781-0.904, p < .001). MRI-DH showed higher absolute values than CT-DH (mean of 1.76 mm). There was a significant association between CT-DH and MRI-ED at L2/3 (p = .006), L3/4 (p = .002), L4/5 (p < .001) and L5/S1 (p < .001). A calculated cut-off point was set at 11 mm. CONCLUSIONS: In the lumbar spine, there is a correlation between disc height on CT and MRI. This can be useful in trauma and emergency cases, where CT is readily available in the lack of an MRI. In addition, in the middle and lower part of the lumbar spine, loss of disc height on CT scans is associated with more pronounced endplate degeneration on MRIs. If the disc height on CT scans is lower than 11 mm, endplate degeneration on MRIs is likely more pronounced. LEVEL AND DESIGN: Level III, a retrospective study.

Dysregulated lipid metabolism and intervertebral disc degeneration: the important role of ox-LDL/LOX-1 in endplate chondrocyte senescence and calcification.

BACKGROUND: Lipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification. METHODS: Human intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated ß-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways. RESULTS: Our study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-κB signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model. CONCLUSIONS: So our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-κB signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD.

Assessment of Tie2-Rejuvenated Nucleus Pulposus Cell Transplants from Young and Old Patient Sources Demonstrates That Age Still Matters.

Cell transplantation is being actively explored as a regenerative therapy for discogenic back pain. This study explored the regenerative potential of Tie2+ nucleus pulposus progenitor cells (NPPCs) from intervertebral disc (IVD) tissues derived from young (<25 years of age) and old (>60 years of age) patient donors. We employed an optimized culture method to maintain Tie2 expression in NP cells from both donor categories. Our study revealed similar Tie2 positivity rates regardless of donor types following cell culture. Nevertheless, clear differences were also found, such as the emergence of significantly higher (3.6-fold) GD2 positivity and reduced (2.7-fold) proliferation potential for older donors compared to young sources. Our results suggest that, despite obtaining a high fraction of Tie2+ NP cells, cells from older donors were already committed to a more mature phenotype. These disparities translated into functional differences, influencing colony formation, extracellular matrix production, and in vivo regenerative potential. This study underscores the importance of considering age-related factors in NPPC-based therapies for disc degeneration. Further investigation into the genetic and epigenetic alterations of Tie2+ NP cells from older donors is crucial for refining regenerative strategies. These findings shed light on Tie2+ NPPCs as a promising cell source for IVD regeneration while emphasizing the need for comprehensive understanding and scalability considerations in culture methods for broader clinical applicability.

A structured biomimetic nanoparticle as inflammatory factor sponge and autophagy-regulatory agent against intervertebral disc degeneration and discogenic pain.

Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration.

Anterior percutaneous full-endoscopic transcorporeal decompression for cervical disc herniation: a finite element analysis and long-term follow-up study.

OBJECTIVE: The purpose of this study was to investigate the long-term consequences on the cervical spine after Anterior transcorporeal percutaneous endoscopy cervical discectomy (ATc-PECD) from the biomechanical standpoint. METHODS: A three-dimensional model of the normal cervical spine C2-T1 was established using finite element method. Subsequently, a disc degeneration model and degeneration with surgery model were constructed on the basis of the normal model. The same loading conditions were applied to simulate flexion, extension, lateral bending and axial rotation of the cervical spine. We calculated the cervical range of motion (ROM), intradiscal pressure, and intravertebral body pressure under different motions for observing changes in cervical spine biomechanics after surgery. At the same time, we combined the results of a long-term follow-up of the ATc-PECD, and used imaging methods to measure vertebral and disc height and cervical mobility, the Japanese Orthopaedic Association (JOA) score and visual analog scale (VAS) score were used to assess pain relief and neurological functional recovery. RESULTS: The long-term follow-up results revealed that preoperative JOA score, neck VAS score, hand VAS score, IDH, VBH, and ROM for patients were 9.49 ± 2.16, 6.34 ± 1.68, 5.14 ± 1.48, 5.95 ± 0.22 mm, 15.41 ± 1.68 mm, and 52.46 ± 9.36° respectively. It changed to 15.71 ± 1.13 (P < 0.05), 1.02 ± 0.82 (P < 0.05), 0.77 ± 0.76 (P < 0.05), 4.73 ± 0.26 mm (P < 0.05), 13.67 ± 1.48 mm (P < 0.05), and 59.26 ± 6.72° (P < 0.05), respectively, at 6 years postoperatively. Finite element analysis showed that after establishing the cervical spondylosis model, the overall motion range for flexion, extension, lateral bending, and rotation decreased by 3.298°, 0.753°, 3.852°, and 1.131° respectively. Conversely, after establishing the bone tunnel model, the motion range for these actions increased by 0.843°, 0.65°, 0.278°, and 0.488° respectively, consistent with the follow-up results. Moreover, analysis of segmental motion changes revealed that the increased cervical spine mobility was primarily contributed by the surgical model segments. Additionally, the finite element model demonstrated that bone tunneling could lead to increased stress within the vertebral bodies and intervertebral discs of the surgical segments. CONCLUSIONS: Long-term follow-up studies have shown that ATc-PECD has good clinical efficacy and that ATc-PECD can be used as a complementary method for CDH treatment. The FEM demonstrated that ATc-PECD can lead to increased internal stresses in the vertebral body and intervertebral discs of the operated segments, which is directly related to cervical spine degeneration after ATc-PECD.

Advances in the interaction between lumbar intervertebral disc degeneration and fat infiltration of paraspinal muscles: critical summarization, classification, and perspectives.

More than 619 million people in the world suffer from low back pain (LBP). As two potential inducers of LBP, intervertebral disc degeneration (IVDD) and fat infiltration of paraspinal muscles (PSMs) have attracted extensive attention in recent years. So far, only one review has been presented to summarize their relationship and relevant mechanisms. Nevertheless, it has several noticeable drawbacks, such as incomplete categorization and discussion, lack of practical proposals, etc. Consequently, this paper aims to systematically summarize and classify the interaction between IVDD and fat infiltration of PSMs, thus providing a one-stop search handbook for future studies. As a result, four mechanisms of IVDD leading to fat infiltration of PSMs and three mechanisms of fat infiltration in PSMs causing IVDD are thoroughly analyzed and summarized. The typical reseaches are tabulated and evaluated from four aspects, i.e., methods, conclusions, benefits, and drawbacks. We find that IVDD and fat infiltration of PSMs is a vicious cycle that can promote the occurrence and development of each other, ultimately leading to LBP and disability. Finally, eight perspectives are proposed for future in-depth research.

Self-powered triboelectric-responsive microneedles with controllable release of optogenetically engineered extracellular vesicles for intervertebral disc degeneration repair.

Excessive exercise is an etiological factor of intervertebral disc degeneration (IVDD). Engineered extracellular vesicles (EVs) exhibit excellent therapeutic potential for disease-modifying treatments. Herein, we fabricate an exercise self-powered triboelectric-responsive microneedle (MN) assay with the sustainable release of optogenetically engineered EVs for IVDD repair. Mechanically, exercise promotes cytosolic DNA sensing-mediated inflammatory activation in senescent nucleus pulposus (NP) cells (the master cell population for IVD homeostasis maintenance), which accelerates IVDD. TREX1 serves as a crucial nuclease, and disassembly of TRAM1-TREX1 complex disrupts the subcellular localization of TREX1, triggering TREX1-dependent genomic DNA damage during NP cell senescence. Optogenetically engineered EVs deliver TRAM1 protein into senescent NP cells, which effectively reconstructs the elimination function of TREX1. Triboelectric nanogenerator (TENG) harvests mechanical energy and triggers the controllable release of engineered EVs. Notably, an optogenetically engineered EV-based targeting treatment strategy is used for the treatment of IVDD, showing promising clinical potential for the treatment of degeneration-associated disorders.

Angina Pectoris Is Associated with Cervical Disc Disease: A Cross-Sectional, Population-Based Study Using the Medicare Expenditure Panel Survey (MEPS).

Atherosclerotic disease in the vessels that supply the cervical spine may lead to degenerative disease. In angina pectoris (AP), atherosclerotic disease leads to coronary vessel occlusion and resulting symptoms. This study aims to determine the relationship between AP and neck pain. Analysis was focused on respondents who had a history of cervical pain disorders, adjusting for demographic, education, and mental health confounders. A total of 30,461 participated in the survey. Of 1,049 respondents, 21% reported neck pain. Mean age of the respondents was 62.6 ± 16.1 years. Nonwhite race, current everyday smokers, lower family income, hypertension, and diabetes had higher prevalence of neck pain (p < 0.05). On multivariate analysis, AP was associated with increased odds of neck pain (odds ratio [OR] = 1.42 [95% confidence interval (CI) 1.04 to 1.92], p = 0.026). AP was independently associated with 42% increased odds of having neck pain. Further study into the association of cardiovascular disease with degenerative disc disease pain should be performed. (Journal of Surgical Orthopaedic Advances 33(2):093-096, 2024).

The role of melatonergic system in intervertebral disc degeneration and its association with low back pain: a clinical study.

Objective: The mechanisms of intervertebral disc degeneration (IVDD) in low back pain (LBP) patients are multiples. In this study, we attempt to investigate whether melatonergic system plays a potential role in IVDD patients with LBP by analyzing their clinical specimens. The fucus will be given to the correlation between the melatonin receptor expression and intervertebral disc tissue apoptosis. Methods: In this clinical study, 107 lumbar intervertebral disc nucleus pulposus (NP) specimens from patients with LBP were collected with patients' consents. The disc height (DH) discrepancy ratio, range of motion and sagittal parameters of the pathological plane were measured and Pfirrmann grade was used to classified the grades of IVDD level. Discs at grades 1-3 were served as normal control and grades 4-5 were considered as IVDD. The expression levels of melatonin receptor 1A (MT1) and 1B (MT2) were measured by immunohistochemistry. The apoptosis of NP was assessed using TUNEL staining. Their potential associations among MT1/2, DH, apoptosis, sagittal parameters with IVDD and LBP were evaluated with statistical analysis. Results: The incidence of IVDD was positively associated with age and negatively related to VAS scores for LBP (p < 0.001). Patients with higher degree of IVDD also have higher DH discrepancy ratio (p < 0.001), higher prevalence of lumbar instability (p = 0.003) and higher cell apoptosis compared to the control. Nevertheless, no statistically significant correlation was identified between Pfirrmann grade and lumbar sagittal parameters. MT1 and MT2 both were highly expressed in the NP tissues. Importantly, MT1 expression but not MT2 was significantly increased in the intervertebral disc tissue of patients with IVDD and its level correlated well with cell apoptosis level and the severity of IVDD as well as lower VAS scores for LBP. Conclusion: The highly elevated MT1 expression was found in NP tissues of patients with IVDD and LBP compared to the control. This phenomenon probably reflects the compensating response of the body to the pathological alteration of the IVDD and LBP. Therefore, these findings provide the novel information to use selective agonists of MT1 to target IVDD and LBP clinically.

Exosomes derived from human urine-derived stem cells ameliorate IL-1ß-induced intervertebral disk degeneration.

BACKGROUND: Human intervertebral disk degeneration (IVDD) is a sophisticated degenerative pathological process. A key cause of IVDD progression is nucleus pulposus cell (NPC) degeneration, which contributes to excessive endoplasmic reticulum stress in the intervertebral disk. However, the mechanisms underlying IVDD and NPC degeneration remain unclear. METHODS: We used interleukin (IL)-1ß stimulation to establish an NPC-degenerated IVDD model and investigated whether human urine-derived stem cell (USC) exosomes could prevent IL-1ß-induced NPC degeneration using western blotting, quantitative real-time polymerase chain reaction, flow cytometry, and transcriptome sequencing techniques. RESULTS: We successfully extracted and identified USCs and exosomes from human urine. IL-1ß substantially downregulated NPC viability and induced NPC degeneration while modulating the expression of SOX-9, collagen II, and aggrecan. Exosomes from USCs could rescue IL-1ß-induced NPC degeneration and restore the expression levels of SOX-9, collagen II, and aggrecan. CONCLUSIONS: USC-derived exosomes can prevent NPCs from degeneration following IL-1ß stimulation. This finding can aid the development of a potential treatment strategy for IVDD.

Rescue of nucleus pulposus cells from an oxidative stress microenvironment via glutathione-derived carbon dots to alleviate intervertebral disc degeneration.

The senescence of nucleus pulposus (NP) cells (NPCs), which is induced by the anomalous accumulation of reactive oxygen species (ROS), is a major cause of intervertebral disc degeneration (IVDD). In this research, glutathione-doped carbon dots (GSH-CDs), which are novel carbon dot antioxidant nanozymes, were successfully constructed to remove large amounts of ROS for the maintenance of NP tissue at the physical redox level. After significantly scavenging endogenous ROS via exerting antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity, GSH-CDs with good biocompatibility have been demonstrated to effectively improve mitochondrial dysfunction and rescue NPCs from senescence, catabolism, and inflammatory factors in vivo and in vitro. In vivo imaging data and histomorphological indicators, such as the disc height index (DHI) and Pfirrmann grade, demonstrated prominent improvements in the progression of IVDD after the topical application of GSH-CDs. In summary, this study investigated the GSH-CDs nanozyme, which possesses excellent potential to inhibit the senescence of NPCs with mitochondrial lesions induced by the excessive accumulation of ROS and improve the progression of IVDD, providing potential therapeutic options for clinical treatment.

Causal relationship between bone mineral density and intervertebral disc degeneration: a univariate and multivariable mendelian randomization study.

BACKGROUND: Although previous studies have suggested a possible association between bone mineral density (BMD) and intervertebral disc degeneration (IDD), the causal relationship between them remains unclear. Evidence from accumulating studies indicates that they might mutually influence one another. However, observational studies may be affected by potential confounders. Meanwhile, Mendelian randomization (MR) study can overcome these confounders to assess causality. OBJECTIVES: This Mendelian randomization (MR) study aimed to explore the causal effect of bone mineral density (BMD) on intervertebral disc degeneration (IDD). METHODS: Summary data from genome-wide association studies of bone mineral density (BMD) and IDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for four potential confounders, body mass index (BMI), Type2 diabetes, hyperthyroidism and smoking. A reverse MR analysis was conducted to assess potential reverse causation. RESULTS: In the univariate MR analysis, femoral neck bone mineral density (FNBMD), heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) had a direct causal effect on intervertebral disc degeneration (IDD) [FNBMD-related analysis: OR(95%CI) = 1.17 (1.04 to 1.31), p = 0.008, eBMD-related analysis: OR(95%CI) = 1.06 (1.01 to 1.12), p = 0.028, LSBMD-related analysis: OR(95%CI) = 1.20 (1.10 to 1.31), p = 3.38E-7,TB BMD-related analysis: OR(95%CI) = 1.20 (1.12 to 1.29), p = 1.0E-8]. In the MVMR analysis, it was revealed that, even after controlling for confounding factors, heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) still maintained an independent and significant causal association with IDD(Adjusting for heel bone mineral density: beta = 0.073, OR95% CI = 1.08(1.02 to 1.14), P = 0.013; Adjusting for lumbar spine bone mineral density: beta = 0.11, OR(95%CI) = 1.12(1.02 to 1.23), P = 0.03; Adjusting for total body bone mineral density: beta = 0.139, OR95% CI = 1.15(1.06 to 1.24), P = 5.53E - 5). In the reverse analysis, no evidence was found to suggest that IDD has an impact on BMD. CONCLUSIONS: The findings from our univariate and multivariable Mendelian randomization analysis establish a substantial positive causal association between BMD and IDD, indicating that higher bone mineral density may be a significant risk factor for intervertebral disc degeneration. Notably, no causal effect of IDD on these four measures of bone mineral density was observed. Further research is required to elucidate the underlying mechanisms governing this causal relationship.

Comparison of robot-assisted versus fluoroscopy-guided transforaminal lumbar interbody fusion (TLIF) for lumbar degenerative diseases: a systematic review and meta-analysis of randomized controlled trails and cohort studies.

BACKGROUND: As an emerging technology in robot-assisted (RA) surgery, the potential benefits of its application in transforaminal lumbar interbody fusion (TLIF) lack substantial support from current evidence. OBJECTIVE: We aimed to investigate whether the RA TLIF is superior to FG TLIF in the treatment of lumbar degenerative disease. METHODS: We systematically reviewed studies comparing RA versus FG TLIF for lumbar degenerative diseases through July 2022 by searching PubMed, Embase, Web of Science, CINAHL (EBSCO), Chinese National Knowledge Infrastructure (CNKI), WanFang, VIP, and the Cochrane Library, as well as the references of published review articles. Both cohort studies (CSs) and randomized controlled trials (RCTs) were included. Evaluation criteria included the accuracy of percutaneous pedicle screw placement, proximal facet joint violation (FJV), radiation exposure, duration of surgery, estimated blood loss (EBL), and surgical revision. Methodological quality was assessed using the Cochrane risk of bias and ROBINS-I Tool. Random-effects models were used, and the standardized mean difference (SMD) was employed as the effect measure. We conducted subgroup analyses based on surgical type, the specific robot system used, and the study design. Two investigators independently screened abstracts and full-text articles, and the certainty of evidence was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: Our search identified 539 articles, of which 21 met the inclusion criteria for quantitative analysis. Meta-analysis revealed that RA had 1.03-folds higher "clinically acceptable" accuracy than FG (RR: 1.0382, 95% CI: 1.0273-1.0493). And RA had 1.12-folds higher "perfect" accuracy than FG group (RR: 1.1167, 95% CI: 1.0726-1.1626). In the case of proximal FJV, our results indicate a 74% reduction in occurrences for patients undergoing RA pedicle screw placement compared to those in the FG group (RR: 0.2606, 95%CI: 0.2063- 0.3293). Seventeen CSs and two RCTs reported the duration of time. The results of CSs suggest that there is no significant difference between RA and FG group (SMD: 0.1111, 95%CI: -0.391-0.6131), but the results of RCTs suggest that the patients who underwent RA-TLIF need more surgery time than FG (SMD: 3.7213, 95%CI: 3.0756-4.3669). Sixteen CSs and two RCTs reported the EBL. The results suggest that the patients who underwent RA pedicle screw placement had fewer EBL than FG group (CSs: SMD: -1.9151, 95%CI: -3.1265-0.7036, RCTs: SMD: -5.9010, 95%CI: -8.7238-3.0782). For radiation exposure, the results of CSs suggest that there is no significant difference in radiation time between RA and FG group (SMD: -0.5256, 95%CI: -1.4357-0.3845), but the patients who underwent RA pedicle screw placement had fewer radiation dose than FG group (SMD: -2.2682, 95%CI: -3.1953-1.3411). And four CSs and one RCT reported the number of revision case. The results of CSs suggest that there is no significant difference in the number of revision case between RA and FG group (RR: 0.4087,95% CI 0.1592-1.0495). Our findings are limited by the residual heterogeneity of the included studies, which may limit the interpretation of the results. CONCLUSION: In TLIF, RA technology exhibits enhanced precision in pedicle screw placement when compared to FG methods. This accuracy contributes to advantages such as the protection of adjacent facet joints and reductions in intraoperative radiation dosage and blood loss. However, the longer preoperative preparation time associated with RA procedures results in comparable surgical duration and radiation time to FG techniques. Presently, FG screw placement remains the predominant approach, with clinical surgeons possessing greater proficiency in its application. Consequently, the integration of RA into TLIF surgery may not be considered the optimal choice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023441600.

Application of network pharmacology and dock of molecules on the exploration of the mechanism of frankincense-myrrh for lumbar intervertebral disc degeneration: A review.

To investigate the efficacy of Frankincense-Myrrh in lumbar Intervertebral degenerative diseases (LIDD). The active components of frankincense-myrrh was retrieved with a unique system pharmacology platform for Traditional Chinese Medicine Systems Pharmacology (TCMSP). The LIDD-related target genes were screened with DisGeNET and Genecards databases. Then, STRING & Cytoscape were used for analyzing the Protein-Protein Interaction network. DAVID was used for analyzing Gene Ontology (GO) & Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, molecules of AutoDockVina and Pymol were used for docking the molecules for verifying active ingredients and key targets' binding force. The 105 LIDD-related targets identified in Ruxiang (RX)-Moyao (MY) involve 53 active ingredients. In addition, topological analysis was conducted for identifying the 12 key targets. According to the analysis results of GO & KEGG, RX-MY is significant for treating LIDD through participating in many pathways and biological processes, such as signaling pathways of inflammatory response reactive process, MAP kinase activity, TNF, and MAPK, etc. According to the dock results, the active components oxo-tirucalic, acid, isofouquierone, (7S, 8R, 9S, 10R, 13S, 14S,17Z)-17-ethylidene-7-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta [a] phenanthrene-3,16-dion in RX-MY binds actively. The basic pharmacological action and RX-MY-related mechanism in the treatment of LIDD was revealed in this study for the first time. It is predicted that the results may provide a treatment plan for RX-MY with replacement of NSAIDs and warrant investigation of new therapeutic alternatives for LIDD. However, these predictions should be validated by relevant pharmacological trials.