Intervertebral disc degeneration (IVDD) represents a prevalent degenerative pathology of the spinal, primarily precipitated by inflammatory processes and the deterioration of extracellular matrix (ECM). Baicalin has an effective anti-inflammatory effect on degenerative diseases. In addition, the P38 mitogen-activated protein kinase (MAPK) signaling pathway plays a crucial role in the pathogenesis of IVDD.

To investigate the therapeutic potential of baicalin in modulating pathological changes in IVDD.

To design an in vitro model of degeneration of nucleus pulposus cells (NPCs) stimulated by IL-1β and an in vivo mouse model of needling to assess the protective effect of baicalin against IVDD and its underlying mechanism.

Baicalin down-regulated inflammatory factors (INOS, COX-2, IL-6) and catabolic factors (MMP-3, MMP-13, ADAMTS-5) while up-regulating anabolic factors (collagen II, SOX-9) by inhibiting the activation of the p38 MAPK signaling pathway, in addition to slowing down the progression of IVDD in the mouse acupuncture model.

Our study demonstrated in vitro experiments that baicalin attenuates IL-1β-stimulated IVDD by inhibiting activation of the P38 MAPK signaling pathway. Meanwhile, the effects of baicalin were also confirmed in vivo experiments, Consequently, we propose that baicalin is a promising therapeutic agent for the treatment of disc degeneration.

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain that incurs large socioeconomic burdens. Growing evidence reveals that macroautophagy/autophagy dysregulation contributes to IVDD, but the exact role of autophagy and its regulatory mechanisms remain largely unknown. Here, we found that mechanical overloading impaired the autophagic flux of nucleus pulposus (NP) cells in vivo and in vitro. Mechanistically, the impairment of autophagic flux was attributed to lysosomal dysfunction induced by overloading. Overloading could also lead to lysosomal membrane permeabilization and consequent lysosome-dependent cell death. As critical effectors of lysosomal quality control pathways, CHMP4B (charged multivesicular body protein 4B) and TFEB (transcription factor EB) were downregulated in overloading-treated NP cells and degenerative discs. Restoring lysosomal function by CHMP4B or TFEB overexpression attenuated autophagic flux impairment of NP cells and protected against overloading-induced IVDD. Additionally, human IVDD was associated with impaired autophagy, and defective lysosomal quality control was also linked to human IVDD. Collectively, these findings highlighted that lysosomal defects were crucial for mechanical overloading-induced autophagic flux impairment and death of NP cells, suggesting the potential therapeutic relevance of restoring lysosomal function for IVDD.Abbreviations: ADAMTS4: ADAM metallopeptidase with thrombospondin type 1 motif 4; Ad: adenovirus; AO: acridine orange; BafA1: bafilomycin A1; CHMP4B: charged multivesicular body protein 4B; CTSD: cathepsin D; CV%: coefficient of variation; DMSO: dimethyl sulfoxide; ESCRT: endosomal sorting complex required for transport; HE: haemotoxylin and eosin; IVDD: intervertebral disc degeneration; LAMP: lysosomal associated membrane protein; LMP: lysosomal membrane permeabilization; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MFI: mean fluorescence intensity; MMP3: matrix metallopeptidase 3; MRI: magnetic resonance imaging; NP: nucleus pulposus; PG: Pfirrmann grade; PI: propidium iodide; RT-qPCR: reverse transcription-quantitative PCR; SOFG: safranin O fast green; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TFEB: transcription factor EB.

To analyze the electromyographic activity (EMG) and thermographic patterns of the masseter and temporalis muscles and pressure of the orofacial tissues in individuals with intervertebral disc degeneration (IDD).

This study had two distinct groups: with IDD (n = 16) and controls (n = 16). EMG at rest, protrusion, right and left laterality, and maximum voluntary contraction were evaluated. Tongue, orbicularis oris, and buccinator muscles pressures were measured by Iowa Oral Performance Instrument. The thermographic patterns were analyzed using infrared thermography.

Comparisons between groups showed significant differences regarding at rest [right (p = 0.05) and left (p = 0.05) masseter and right temporal (p = 0.05)], orofacial tissue pressure [tongue (p = 0.001), orbicularis oris (p = 0.01), and buccinator (p = 0.0001)], but no significant differences for the thermographic patterns.

IDD modifies the functionality of the craniomandibular complex, influencing the performance of the stomatognathic system.

Assessing the bone condition in patients with spinal disease is clinically valuable. However, evaluating bone strength in the presence of spine degenerative changes is challenging. Quantitative computed tomography (QCT) and finite element analysis (FEA) have been proposed as methods for more accurate bone quality assessment. This study investigates the relationship between bone strength predicted by FEA and other relevant biological parameters. This retrospective cross-sectional study included 127 patients with spinal disease who underwent preoperative CT scans between 2014 and 2020. Baseline patient characteristics, volumetric bone mineral density (vBMD) measured by QCT, and vertebral bone strength predicted by FEA were collected. The degree of degeneration was evaluated by classifying osteophyte formation, disc height narrowing, vertebral sclerosis, and spondylolisthesis into a grading scale ranging from 0 to 2. Multiple linear regression analysis was conducted to assess the effect of each factor on bone strength predicted by FEA. Of 127 patients, 120 patients (median age was 62 years) were included. The median vBMD and vertebral strength were 114.3 mg/cm3 and 7892.9 N, respectively. After adjusting for age, sex, body mass index, smoking status, diabetes mellitus, vBMD, and degenerative changes, multiple linear regression analysis revealed that sex, vBMD, and degree of degeneration independently increased the vertebral strength measured by FEA. This study suggests that in patients with spinal disease, vertebral bone strength is affected not only by sex and bone mineral density but also by degenerative changes. Thus, bone strength could be predicted more accurately in patients with spinal disease using FEA.

The assessment of disc degeneration remains a significant challenge in clinical research. Pfirrmann grade is a frequently used classification for lumbar disc degeneration on MRI. However, there has been no gold standard for cervical spine disc degeneration. Recently, we introduced the Disc Signal Intensity Index (DSI2) as a quantitative disc assessment for the lumbar spine, which is easily measurable in the cervical spine.

The aim of this study was to apply DSI2 in the cervical intervertebral disc and investigate the factors associated with the cervical disc degeneration.

Cross-sectional study using retrospectively collected data.

Cervical MRIs from a database of patients undergoing ACDF between 2015 and 2018 were retrospectively reviewed.

Demographic variables included age, sex, body mass index (BMI), race, smoking status, and comorbidities such as diabetes, chronic kidney disease, and coronary artery disease.

DSI2 measurements were performed on midsagittal T2-weighted MRI images by determining the intensity within regions of interest (ROI). One ROI was set in the cerebrospinal fluid (CSF) and three ROIs were set per disc at the anterior, middle, and posterior third. The mean of the three measurements per disc was then divided by that of the CSF to calculate the DSI2 score. Multivariable linear regression analyses with mixed model were conducted to determine the potential contributing factors for disc degeneration.

A total of 149 patients and 770 discs were included in the final analysis. Ninety-three patients (37.6%) were female and the mean (SD) age was 55.6 (11.7) years. The distribution of DSI2 scores among the different Pfirrmann grades was as follows: Grade 1: 0.259±NA; Grade 2: 0.226±0.090; Grade 3: 0.175±0.070; Grade 4: 0.136±0.060; Grade 5: 0.131±0.050. Multivariable linear mixed-effect regression analysis, setting with DSI2 as the objective variable, demonstrated that age (β=-0.130, p<.05), BMI (β=-2.06, p<.05), Modic changes (Type1 β= -2.70, p<.01) were independent contributors to disc degeneration. The segments C4/5 and C7/T1 were less prone to disc degeneration (C4/5: β=1.37, p<.001; C7/T1: β=2.63, p<.001) and the history of diabetes (β=5.31, p<.01) was associated with high DSI2.(p<.01).

The present study provides valuable insights for identifying risk factors in degenerative cervical conditions utilizing the DSI2. The DSI2 method emerges as a promising alternative for future disc research, excelling in the detection of subtle progressions of degeneration and distinguishing itself from the subjective Pfirrmann grading system.

The collagen and elastin are important components of extracellular matrix (ECM) in the nucleus pulposus (NP), which can produce water-insoluble proteins through cross-linkages to stabilize ECM. Lysyl oxidase (LOX), a copper-dependent amine oxidase, insolubilizes ECM proteins to keep the stability of ECM by initiating collagen and elastin cross-linkages. The present study aimed to investigate the relationships between intervertebral disc (IVD) degeneration and LOX expression in human NP. A total of 22 cases with lumbar IVD degeneration were designed to the observed group and the control group consisted of 4 young patients with the need of surgically removing the IVD due to lumbar vertebra fracture caused by sudden trauma. These patients were grouped based on Pfirrmann grades of IVDs. The control group represented grade I (group A) and the observed group was subdivided into 4 group: Grade II (group B), grade III (group C), grade IV (group D) and grade V (group E). The herniated NP of each group was prepared for immunohistochemistry, western blotting and reverse transcription-quantitative PCR. The present results showed that the number of NP cells and the components of ECM were significantly lower in the observed group than in the control group. There was an inverse association of the expression rate of LOX NP cells with Pfirrmann grades and age. The protein expression of LOX in group A, B, C, D and E was 2.69±0.24, 2.24±0.32, 1.34±0.19, 1.3±0.32 and 1.01±0.12, respectively. The mRNA expression of LOX in Group A, B, C, D and E was 1±0.03, 0.83±0.07, 0.71±0.09, 0.53±0.09 and 0.27±0.05, respectively. With increasing IVD degeneration, the protein and mRNA expression levels of LOX in NP decreased gradually. Taken together, the findings of the present study revealed that the protein and mRNA expression levels of LOX were decreased with increasing IVD degeneration. These findings provide new insights that LOX might involve in the occurrence and development of IVD degeneration.

This study aims to use ultrasound guidance to locate the intervertebral disc (IVD) of a mouse caudal spine, establish a mouse model of IVD herniation by needle puncture and cyclic pump pressure, and perform ultrasound to longitudinally detect paravertebral tissue swelling to help evaluate the pathological progression after IVD herniation.

An animal ultrasound was used to scan the caudal spine of mice to locate the IVDs. IVD herniation was induced in the mice by puncturing the caudal IVDs (Co4/5, Co5/6, and Co6/7) with a 26-G needle and applying cyclic pump pressure using an improved microinjection pump. Magnetic resonance imaging (MRI) was used to detect IVD degeneration, and ultrasound was performed to assess swelling in the paravertebral tissue before and at one, two, and four weeks after surgery. Additionally, a parallel cross-sectional cohort of mice was euthanized at each time point. Alcian Blue/Orange staining was utilized to evaluate inflammation, and immunofluorescence staining detected the location of nucleus pulposus (NP) cells in the IVDs. Finally, the relationship between swelling volume and inflammation or IVD degeneration was evaluated using linear regression analysis.

The IVD was identified based on the pixel of ultrasound images, which aligns with the IVD location for AB/OG staining in the IVDs. In the mouse model of IVD herniation, a bilateral rupture of the annulus fibrosus and the herniation of the NP tissue into the paravertebral tissue were observed 24 h after surgery. The Pfirrmann grade and peak separation value from magnetic resonance T2 weighted (MRT2) images showed that the IVD degenerated one week after surgery compared to before surgery (grade 1 and 3, P < 0.0001; P = 0.001). There was no significant difference between one and two weeks post-surgery (grade 3 and 3, P = 0.851; P = 0.469). However, a difference was observed between two and four weeks post-surgery in the Pfirrmann grade and peak separation value (grade 3 and 4, P = 0.037; P = 0.011). Additionally, there was a strong negative correlation (r = - 0.875, P < 0.0001) between the Pfirrmann grade and the peak separation value. Meanwhile, paravertebral tissue swelling and inflammation peaked one week after surgery (P < 0.0001; P < 0.0001), decreased at two weeks (P < 0.0001; P = 0.004), and reduced further by four weeks (P = 0.001; P = 0.270). Furthermore, there was a stronger correlation between paravertebral tissue swelling and inflammation (r = 0.832, P < 0.0001) compared to the Pfirrmann grade (r = 0.364, P = 0.041) or the peak separation value (r = - 0.324, P = 0.007).

Ultrasound can guide IVD localization, which may assist in establishing a mouse model of IVD herniation. Additionally, ultrasound can provide longitudinal measurements of swelling in paravertebral tissue, which may contribute to the pathological investigation of IVD herniation.

Magnetic Resonance Elastography (MRE) is a non-invasive imaging technique that quantifies tissue stiffness by analyzing shear wave propagation. While MRE is widely used in hepatic imaging, its application in the lumbar spine remains an emerging field. Understanding the repeatability and reproducibility of MRE measurements in the lumbar spine is crucial for its clinical implementation. This scoping review aims to summarize current evidence on the use and applicability of MRE for assessing lumbar spine structures, including intervertebral discs and paraspinal muscles.

A systematic literature search was conducted in MEDLINE (PubMed), CINAHL, Embase, and The Cochrane Library. Studies investigating MRE of the lumbar spine in adult populations were included. Key aspects such as MRE acquisition methods, repeatability and reproducibility of measurements, and study heterogeneity were assessed. Extracted data were categorized based on study design, imaging techniques, and primary outcomes related to lumbar stiffness assessment.

This review identified 11 relevant studies. These studies demonstrated the capability of MRE to characterize shear stiffness in the lumbar intervertebral discs and paravertebral muscles, in both resting states, across various muscle conditions, and under different interventions such as physical activity and therapeutic taping. The review documents the heterogeneous methodological approaches of the studies, highlighting the innovative but varied approaches to this field. Due to this, diverse findings were reported, some of which were contradictory.

The current evidence of MRE of the lumbar spine is promising though limited due to heterogeneous study methodologies. Future research should focus on larger, multicenter studies with standardized protocols. Despite the current limitations in evidence, MRE holds potential for non-invasive lumbar spine assessment and further research validation.

Surgical technique and the clinical outcomes of intersegmental fixation with an interspinous spacer (IFIS) for lumbar spinal instability are reported in this study. Four patients underwent surgery using this procedure. There were no surgical complications, and the clinical outcomes were satisfactory. Spinal alignment was maintained successfully as observed radiographically, and bone fusion was obtained in all cases. This technique may be an alternative for patients with degenerative lumbar disease such as spondylolisthesis and lumbar spinal stenosis (LSS) with mild spinal instability.

Lumbar disc herniation is primarily caused by intervertebral disc degeneration (IVDD). Nucleus pulposus (NP) cell dysfunction leads to pro-inflammatory cytokines secretion increase, causing extracellular matrix (ECM) degradation. ECM is essential for maintaining normal disc function. Glycoprotein (Transmembrane) Nmb (GPNMB) is strongly associated with inflammation, and its expression and effects in IVDD are unclear. We categorized 40 clinically collected IVDD samples using the magnetic resonance imaging (MRI)-based Pfirrmann grading system. GPNMB mRNA expression was notably suppressed in patients with severe IVDD compared with patients with mild IVDD. Increased GPNMB mRNA expression correlated with decreased Interleukin-6 (IL-6) expression and increased collagen type II (COL2A1) expression levels. We utilized lentivirus to overexpress GPNMB in IL-1β-induced NP cells to explore its function in IVDD. GPNMB overexpression inhibited pro-inflammatory cytokines Tumor necrosis factor-alpha and IL-6 secretion in IL-1β-induced NP cells, while anti-inflammatory cytokine IL-10 content was increased. In addition, GPNMB overexpression inhibited NP ECM degradation by decreasing ECM-degrading enzymes matrix metalloproteinases-3/13 and a disintegrin and metalloproteinase with thrombospondin motifs-4/5 in vitro. Mechanism studies revealed that GPNMB was bound to CD44, a receptor expressed on the NP cell surface. GPNMB overexpression inhibited nuclear factor-κB (NF-κB) p65 phosphorylation and nuclear translocation in vitro, possibly through CD44. In conclusion, GPNMB suppressed the expression of pro-inflammatory cytokines and ECM degradation in NP cells by inhibiting activation of NF-κB.

Intervertebral disc degeneration (IDD) remains a global healthcare challenge. Here, by analyzing clinical samples, we discover the loss of milk fat globule-EGF factor 8 (MFG-E8) from the nucleus pulposus (NP) tissue-along with increased enzymatic breakdown of glycosaminoglycans (GAGs)-as an overlooked factor for IDD development. Repairing the degraded NP extracellular matrix (ECM) with a structurally-mimicking glycan glue to enrich MFG-E8 may counter the degeneration. Accordingly, we synthesize a glucomannan octanoate (GMOC) with robust resistance to ECM-cleaving enzymes, which forms assemblies with MFG-E8 to maintain a healthy NP cell phenotype. GMOC injected into the degenerated intervertebral disc enriches MFG-E8 in situ, leading to NP tissue regeneration in a rat and a rabbit model, which represent two clinical scenarios of pre-surgical intervention and post-surgical regeneration of IDD, respectively. In summary, we report enriching MFG-E8 in ECM with a glycan glue as a mechanism to promote NP regeneration for IDD treatment.

Macrophages eliminate apoptotic cells produced daily in the body through efferocytosis. Restricted clearance can cause inflammation-related diseases. In intervertebral discs (IVDs), apoptotic nucleus pulposus cells (NPCs) are difficult to effectively remove, and their accumulation can cause changes in the inflammatory microenvironment, disrupt IVD homeostasis, and lead to IVD degeneration (IDD). Here, we present chimeric antigen receptor-M-like engineered macrophages (CAR-eMs) with enhanced efferocytosis capacity for IDD treatment. Macrophages undergo phenotypic transformation and a reduction in phagocytic ability after phagocyting apoptotic NPCs, but their efferocytosis capacity recovers with upregulated brain-specific angiogenesis inhibitor 1 (BAI1) expression. We develop a CAR-eM system with enhanced BAI1 expression and an IVD circular microneedle (MN) delivery system that utilizes arrays of MNs to deliver CAR-eMs into the deep IVD layers, thereby clearing apoptotic NPCs, ameliorating the inflammatory microenvironment, and repairing damaged IVDs. Our study explores the therapeutic potential of CAR-eM efferocytosis for IDD treatment.

Regenerative medicine represents a transformative approach to treating nucleus pulposus degeneration and offers hope for patients suffering from chronic low back pain due to disc degeneration. By focusing on restoring the natural structure and function of the nucleus pulposus rather than merely alleviating symptoms, these innovative therapies hold the potential to significantly improve patient outcomes. As research continues to advance in this field, we may soon witness a paradigm shift in how we approach spinal health and degenerative disc disease. The main purpose of this review is to provide an overview of the various regenerative approaches that target the restoration of the nucleus pulposus, a primary site for initiation of intervertebral disc degeneration.

Background: Degenerative disk disease (DDD) is a progressive condition that occurs when the intervertebral discs (IVDs), which act as shock absorbers between the vertebrae, degenerate or wear out. Due to this degeneration process, the mechanical properties of the IVD, providing flexibility between adjacent vertebrae, can change. Thus, assessing these mechanical properties may improve diagnosis and treatment guidance for DDD. In this article, we tested in vivo multifrequency magnetic resonance elastography (MMRE) of the human IVD in identifying progressively DDD in three asymptomatic male volunteers aged 32, 50, and 60 years. Methods: MMRE of the lumbar spine was acquired using a dual-actuator setup and operated at four frequencies from 60 to 90 Hz. MMRE data were postprocessed using multifrequency wave-number recovery (k-MDEV) inversion algorithm. The resulting shear wave speed (SWS) values were used as a surrogate parameter of tissue stiffness and then compared to Pfirrmann grading (Pf) of disc degeneration (1-5) performed by an experienced MRI spine researcher. Results: Morphological Pf demonstrated an inverse relationship between increasing IVD stiffness and progressive IVD degeneration by a Spearman's rank correlation coefficient of ρ = -0.792, p < 0.001. Conclusion: MMRE allows measurement of in vivo mechanical properties of IVDs and may provide additional information in disc degeneration beyond standard morphological changes. Prior to the clinical use of this technique, future studies should be conducted to evaluate the reproducibility and repeatability of spinal MMRE in the spine, and particularly its potential confounders.

Degeneration of intervertebral discs and facet joints are common conditions that are thought to be interrelated. This study aimed to investigate the morphological interplay between disc and facet degeneration, as well as relationships between adjacent discs and facets. This prospective study involved 712 participants (307 males, 405 females) categorized into three groups: no back pain (no-BP), intermittent (iLBP), and chronic low back pain (cLBP). The Pfirrmann classification was used to assess intervertebral disc degeneration of index and adjacent segments, while the Fujiwara classification evaluated facet joint degeneration. Spearman's correlation coefficient analyzed relationships between degenerative changes in discs and facets. Overall, from the 712 participants 254 were with no-BP, 159 with intermittent LBP, and 299 with chronic LBP. The severity of both intervertebral disc and facet joint degeneration in the MRI sequences increased from upper to lower segments, with a significant clear directionality in differences between the uppermost and lowermost levels (p < 0.01). A strong positive correlation was observed between degenerative changes of adjacent intervertebral discs, especially in the upper and middle lumbar spine (ρ > 0.69). However, correlations between intervertebral disc and facet joint degeneration were weak in all populations studied (ρ < 0.31). The data indicate a directionality in the disease progression, with a strong correlation observed between adjacent intervertebral discs, suggesting a concurrent degenerative process. In contrast, the weak correlations between disc and facet joint degeneration imply that these structures undergo independent degenerative processes, particularly in the early stages of degeneration. Further research is essential to elucidate the underlying mechanisms and to develop precise therapeutic interventions for lumbar spine degeneration.

This study aims to investigate whether Hounsfield unit (HU) value is correlated with intervertebral disc (IVD) degeneration (IVDD) by comparing premenopausal with menopausal women patients.

A total of 101 female patients who underwent treatment in our hospital between February 2022 and February 2023 were retrospectively reviewed and included in this study. All patients were divided into either the premenopausal group or the menopausal group, according to age and menopause status. The changes in disc height index (DHI) on X-ray, the Hounsfield unit (HU) value on computed tomography (CT), and the area of the nucleus pulposus (NP) on magnetic resonance imaging (MRI) were assessed and compared between the two groups.

There is a significant difference in the Pfirrmann grading of T12-S1 discs between the premenopausal and menopausal groups; the menopausal group has more degenerated discs compared with the premenopausal group (P < 0.001). There is no significant difference in DHI measurements between the premenopausal and menopausal groups. HU values in the premenopausal group are greater compared with the menopausal group from T12 to S1 vertebrae (all P < 0.001). Regarding the NP area on MRI, the L2-L3 IV disc space have a bigger area in the premenopausal group compared with the menopausal group (P = 0.029), with no significant difference in other IVD segments.

The HU value on CT is significantly decreased with IVDD progression after menopause. The change in HU value could indirectly reflect vertebral bone mineral density. Therefore, the decline of estrogen after menopause leads to vertebral osteoporosis, which might contribute to IVDD progression.

Retrospective cohort study.

To analyze the correlation between intervertebral vacuum phenomenon (IVP) severity and total endplate damage score [total endplate score (TEPS)].

IVP severity and the TEPS are degenerative changes of the disc and endplate, respectively.

We retrospectively analyzed a cohort of patients undergoing lumbar fusion surgery due to degenerative disease between 2013 and 2021. Computer tomography was used to classify the severity of the IVP at each lumbar level and as a combined lumbar score (Lumbar Vacuum Severity Scale). Magnetic resonance imaging was used to classify endplate degeneration by the TEPS. The correlation between the combined lumbar IVP and TEPS was analyzed through a multivariable regression model.

A total of 317 patients were analyzed with a median age of 63 years (interquartile range: 55-71.2), and 48.9% (n = 155) were females. In all lumbar levels, the median TEPS was 4 (interquartile range: 2-8). The severity of the TEPS was significantly associated with an increased odds ratio (OR) of having more severe IVP (OR: 1.78, 95% CI: 1.62-1.95, P < 0.001). After adjusting for multiple confounders, this relationship remained significant (OR: 1.32, 95% CI: 1.17-1.49, P < 0.001). Other independent significant influences were age (OR: 1.07, 95% CI: 1.04-1.10, P < 0.001) and the Pfirrmann grade (OR: 7.44, 95% CI: 4.40-12.58, P < 0.001). The analysis of the relationship between the combined lumbar vacuum score and lumbar endplate score was significant, with a beta-coefficient (β) of 0.24 (95% CI: 0.20-0.28, P < 0.001).

We found a significant correlation between IVP and TEPS in patients undergoing spine fusion surgery. These results support the theory that endplate damage could play a role in the pathogenesis of IVP.

The cartilaginous endplate (CEP) plays a pivotal role in facilitating the supply of nutrients and, transport of metabolic waste, as well as providing mechanical support for the intervertebral disc (IVD). Recent technological advances have led to a surge in MR imaging studies focused on the CEP. This article describes the anatomy and functions of the CEP as well as MRI techniques for both qualitative and quantitative assessment of the CEP. Effective CEP MR imaging sequences require two key features: high spatial resolution and relatively short echo time. High spatial resolution spoiled gradient echo (SPGR) and ultrashort echo time (UTE) sequences, fulfilling these requirements, are the basis for most of the sequences employed in CEP imaging. This article reviews existing sequences for qualitative CEP imaging, such as the fat-suppressed SPGR and UTE, dual-echo subtraction UTE, inversion recovery prepared and fat-suppressed UTE, and dual inversion recovery prepared UTE sequences. These sequences are employed together with other techniques for quantitative CEP imaging, including measurements of T2*, T2, T1, T1ρ, magnetization transfer, perfusion, and diffusion tensor parameters. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

This study aims to investigate the relationship between interspinous ligament fluid (ISF) sign and low back pain, and the effect of ISF on the outcome of lumbar interbody fusion (LIF).

This retrospective analysis evaluated patients who underwent single-level LIF for lumbar degeneration from January 2012 to December 2019. Patients were divided into ISF (+) and ISF (-) groups based on preoperative lumbar MRI. Data collected included demographic information, surgical data, preoperative and postoperative VAS and ODI scores, and surgical satisfaction. Imaging data assessed intervertebral disc degeneration, lumbar spondylolisthesis, and stability of surgical segments. Differences in VAS, ODI, and satisfaction scores before and after surgery were compared, and regression analysis identified imaging factors linked to residual low back pain. Two-sided p < 0.05 was considered statistically significant.

A total of 328 patients participated in the study, with 108 in the ISF (+) group and 220 in the ISF (-) group. There were no significant differences in mean age, BMI, sex ratio, hypertension, or diabetes rates between the groups. However, the ISF (+) group had a significantly longer hospital stay (16.13 ± 6.83 days) compared to the ISF (-) group (14.51 ± 6.59 days) (p = 0.040). No significant differences were found in operative level, operation time, intraoperative blood loss, or complication rates. At 1 and 3 months postoperatively, VAS scores for low back pain were significantly higher in the ISF (+) group than in the ISF (-) group (p < 0.001 for both). ODI scores showed no significant differences at any postoperative time point (p > 0.05). A significant difference was observed in the proportion of patients with residual low back pain at both 1 and 3 months post-surgery, with more patients in the ISF (+) group reporting pain. Residual low back pain at 1 and 3 months post-surgery positively correlated with a positive ISF sign at the preoperative fusion level (R = 0.213, p < 0.001; R = 0.123, p = 0.025). Logistic regression analysis indicated that a positive ISF sign at the preoperative fusion level was an independent risk factor for residual low back pain at both 1 month and 3 months post-surgery [OR (95% CI) = 2.528 (1.552, 4.118), p < 0.001; OR (95% CI) = 2.146 (1.076, 4.277), p = 0.030].

A positive ISF sign observed at the fusion level may significantly influence the outcomes of lumbar fusion procedures. Specifically, the presence of a positive ISF sign is associated with an elevated risk of unfavorable early postoperative results following lumbar fusion. Furthermore, patients exhibiting a positive ISF sign are more likely to experience residual low back pain during the early postoperative phase compared to those with a negative ISF sign.

Study DesignCross sectional comparative study.ObjectivesThe current study aims to explore the calcification potential (BMP2 expression) of intervertebral discs and its association with the presence of vertebral endplate defects visible on MRI.MethodsForty-seven herniated lumbar disc samples obtained from patients aged 20-76 (31 M/16F) undergoing surgery. Five-µm thin sections were stained with H&E in order to assign a histological degeneration score (HDS) from 0-15 on the basis of cell density (0-5), structural alterations (0-4), granular changes (0-3) and mucus degeneration (0-3). Sections were immuno-stained with anti BMP-2 antibodies to observe the calcification potential in these discs. In addition, pre-operativeT2-T1 W MRI images of the lumbar spine were analyzed for the presence and type (typical or atypical) of vertebral endplate defects, grade of disc degeneration (Pfirrmann grade I-V), presence of high intensity zones (HIZ), and Modic changes at the operated level.ResultsVertebral endplate defects, Modic changes & HIZ were observed in 81%, 29% and 21% of patients respectively. Mean HDS & BMP-2 expression was 9 ± 2 and mean 71 ± 36 spots/mm2 respectively. Discs with adjacent vertebral endplate defects showed increased cell density (P = .004), mucus degeneration (P = .002), HDS (P = .01) and BMP-2 expression (P = .01). Discs with HIZ also had increased HDS, but significance was seen with increased BMP2 expression (P = .006). HDS showed a positive correlation with BMP 2 expression (r = .30, P = .04).ConclusionThese findings suggest that the altered mechanical environment of discs is strongly associated with BMP-2 expression which is an important marker of intervertebral disc calcification.

A secondary analysis of data from the NORDSTEN-spinal stenosis trial (SST).

The aim of the present study was to investigate whether the dural sac cross-sectional area (DSCA) on magnetic resonance imaging (MRI) of adjacent segments decreases after decompressive surgery due to lumbar spinal stenosis (LSS) up to 2 years postoperatively and to investigate possible associations with baseline variables, including preoperative patient and radiological characteristics, and surgical method used.

Decompressive surgery for LSS is currently the most common spinal surgery procedure; however, there is limited knowledge of changes in the DSCA over time adjacent to a decompressed segment.

In the NORDSTEN-SST, 437 patients were randomized to decompression with one of three minimally invasive surgical methods for LSS. The patients underwent an MRI of the lumbar spine (L2-L5) before surgery and at 3 and 24 months postoperatively. Descriptive statistics of adjacent DSCA and changes in adjacent DSCA are presented. Possible prognostic factors (preoperative factors, radiologic measures, and surgical method) for changes in the adjacent DSCA were examined using multivariate regression analyses.

Three hundred twenty-two patients (74%) in the original NORDSTEN-SST had undergone MRI at both 3 and 24 months postoperatively and were included (360 adjacent levels, 263 cranial, and 97 caudal to a decompressed level). Up to two years postoperatively, no decrease in adjacent DSCA was observed. No associations were found between the investigated baseline variables and DSCA change from zero to two years, except for a weak association with baseline adjacent DSCA.

Up to two years postoperatively, the DSCA did not decrease at adjacent levels after decompressive surgery. None of the investigated baseline variables showed any clinically meaningful prognostic value regarding adjacent DSCA changes two years postoperatively. The findings support previous reports that decompression of adjacent levels is not required to prevent subsequent stenosis.

Discectomy-induced ferroptosis of nucleus pulposus cells (NPCs) contributes to postoperative lumbar disc herniation (LDH) recurrence and intervertebral disc degeneration (IDD). We discover that nucleus pulposus progenitor cells (NPPCs) could imprint ferroptosis resistance into NPCs through exosome-dependent intercellular transmission of miR-221-3p. Based on these findings, we first develop synthetically-tailored NPPC-derived exosomes with enhanced miR-221-3p expression and NPC uptake capacity, which are integrated into an injectable hydrogel based on extracellular matrix (ECM) analogues. The ECM-mimetic hydrogel (HACS) serves as a biomimetic filler for the post-operative care of herniated discs, which could be facilely injected into the discectomy-established nucleus pulposus (NP) cavity for localized treatment. HACS-mediated in-situ exosome release in the NP cavity enables marked ferroptosis inhibition in NPCs that not only prevents LDH recurrence but also reverses the IDD symptoms, leading to robust restoration of NP structure and functions. In summary, this study offers a promising approach for treating disc herniation.

Chronic back pain is a long-lasting disorder that is significantly associated with a reduction in the quality of life. Previously, the efficacy of intradiscal and epidural injections of plasma rich in growth factors (PRGF) was demonstrated at 6 months. The objective of this study was to retrospectively examine the medical records of these patients in order to determine whether the observed improvement at the 6-month follow-up was sustained over time.

PRGF efficacy was evaluated using validated questionnaires: Core Outcome Measure Index (COMI) Pain score, COMI Disability score, COMI total score, and Oswestry Disability Index (ODI). Furthermore, an evaluation was conducted to determine whether the patients had undergone additional treatments.

the results demonstrated that 85.2% of the 27 patients who were enrolled exhibited sustained improvement across all scales over a median follow-up period of 24 months. The results of all questionnaires administered at 24 months exhibited statistically significant differences when compared to the baseline data (p < 0.01). Furthermore, there were no statistically significant differences between the results reported at 6 months and those at 24 months (p > 0.05).

the results of this retrospective study demonstrate that treatment of chronic back pain with PRGF was effective in maintaining pain reduction and improving function for at least 24 months after the end of treatment.

Study DesignA prospective study.ObjectivesThis study aims to explore the correlation between interleukin (IL)- 6 levels in intervertebral disc (IVD) tissue and clinical outcomes in patients undergoing lumbar surgery for lumbar degenerative disease (LDD).MethodsThis prospective study analyzed 32 patients (22 men and 10 women, average age 69.6 years) who underwent lateral lumbar interbody fusion (LLIF). IL-6 gene expression in IVD tissues collected during surgery was measured and correlated with pre- and postoperative clinical outcomes, including pain intensity assessed via Numeric Rating Scales (NRS) and quality of life (QOL) evaluated through the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ).ResultsIL-6 levels showed statistical correlations with postoperative intensity of low back pain (LBP) and several JOABPEQ domains. Patients with higher expression of IL-6 levels experienced more severe postoperative LBP and lower scores in lumbar function, walking ability, social life function, and mental health. The effectiveness rate of JOABPEQ scores was exceptionally high for low back pain (.548), walking ability (.677), and social functioning (.563), demonstrating the effectiveness of LLIF. The average operation time was 105.6 minutes, and the estimated blood loss was 85.6 mL.ConclusionsThe study underscores IL-6 as a potential biomarker for predicting surgical outcomes in LDD. High IL-6 levels correlate with worse postoperative LBP and lower QOL scores. Integrating molecular markers like IL-6 with patient-reported outcomes could provide a more comprehensive approach to postoperative care in spinal disorders, aiming to improve the overall QOL for LDD patients undergoing LLIF surgery.

This study aimed to develop a graph neural network (GNN) for automated three-dimensional (3D) magnetic resonance imaging (MRI) visualization and Pfirrmann grading of intervertebral discs (IVDs), and benchmark it against manual classifications. Lumbar IVD MRI data from 300 patients were retrospectively analyzed. Two clinicians assessed the manual segmentation and grading for inter-rater reliability using Cohen's kappa. The IVDs were then processed and classified using an automated convolutional neural network (CNN)-GNN pipeline, and their performance was evaluated using F1 scores. Manual Pfirrmann grading exhibited moderate agreement (κ = 0.455-0.565) among the clinicians, with higher exact match frequencies at lower lumbar levels. Single-grade discrepancies were prevalent except at L5/S1. Automated segmentation of IVDs using a pretrained U-Net model achieved an F1 score of 0.85, with a precision and recall of 0.83 and 0.88, respectively. Following 3D reconstruction of the automatically segmented IVD into a 3D point-cloud representation of the target intervertebral disc, the GNN model demonstrated moderate performance in Pfirrmann classification. The highest precision (0.81) and F1 score (0.71) were observed at L2/3, whereas the overall metrics indicated moderate performance (precision: 0.46, recall: 0.47, and F1 score: 0.46), with variability across spinal levels. The integration of CNN and GNN offers a new perspective for automating IVD analysis in MRI. Although the current performance highlights the need for further refinement, the moderate accuracy of the model, combined with its 3D visualization capabilities, establishes a promising foundation for more advanced grading systems.

Condoliase-based chemonucleolysis and microendoscopic discectomy (MED) are considered to be minimally invasive treatments for lumbar disc herniation (LDH). The aim of this study was to compare the clinical outcomes of both treatments, specifically focusing on whether the outcomes vary by age group.

Patients with LDH who received intradiscal condoliase injections (condoliase group) or underwent MED (MED group) with 1-year follow-up were enrolled in this study. A numerical rating scale (NRS) was developed for leg and back pains. Using magnetic resonance imaging, changes in disc height and degeneration were evaluated. The data were assessed at baseline and at 3-month and 1-year follow-ups. The therapy was considered effective in patients whose NRS for leg pain improved by ≥50% at 1 year from baseline and for whom surgery was not required. Comparative analyses were conducted between the condoliase and MED groups and among the <20, 20-39, 40-59, and ≥60 year age groups.

In this study, a total of 345 patients (condoliase group, n=233; MED group, n=112) were enrolled. Subsequent surgery was required in 23 patients (9.9%) in the condoliase group because of the ineffectiveness of the condoliase therapy. Because of herniation recurrence, reoperation was required in five patients (4.5%) in the MED group. The efficacy rates were respectively 74.4% and 74.6% in the condoliase and MED groups, and no intergroup or age-group differences were found. The condoliase group had a significantly higher decrease in disc height when compared with the MED group (9.0% vs. 4.4%, p<0.05). Compared with the older age group, the younger age group had a greater decrease in disc height and disc degeneration; however, their recovery was better than that of the older age group. Among the age groups, the herniation reduction rate did not significantly vary.

Condoliase and MED had equivalent 1-year outcomes, with no differences observed in efficacy across age groups. For informed decision-making, the advantages and disadvantages of each treatment must be understood.

Intervertebral disc degeneration (IVDD) is characterized by a decrease in extracellular matrix (ECM) and water loss, which is a major cause of low back pain (LBP). Electroacupuncture (EA) has long been used to relieve LBP in IVDD. To investigate whether EA can upregulate aquaporins (AQPs) in IVDD via the cAMP/PKA pathway in a rabbit model of disc degeneration.

A homemade loading device was adapted to trigger a disc degeneration model. After 28 days, EA treatment was performed. Magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) were performed to evaluate AQP content and water diffusion. AQP protein expression in the slices was observed by Western blot and immunofluorescence (IF) staining. The pathology of the intervertebral discs was determined by staining. cAMP and PKA levels were examined using ELISA, and the expression of AQP genes as well as the cAMP/PKA pathway and its related molecules were examined using quantitative reverse transcription-PCR (qRT-PCR) and Western blot analysis.

The EA intervention reduced MRI Pfirrmann scores, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) values. EA can upregulate the expression of AQP1 and AQP3, thereby improving the pathological morphology of the nucleus pulposus (NP) and the cartilage endplate of the intervertebral disc. cAMP and PKA levels were significantly increased after EA intervention in rabbits with IVDD. EA intervention can partially improve the expression of related molecules in the cAMP/PKA pathway, but H-89 reverses the effect of EA.

EA can attenuate intervertebral disc degeneration by regulating AQP expression, a process that may be mediated by the cAMP/PKA pathway.

Low back pain (LBP) is a leading cause of disability worldwide, with up to 25% of cases become chronic (cLBP). Whilst multi-factorial, the relative importance of contributors to cLBP remains unclear. We leveraged a comprehensive multi-dimensional data-set and machine learning-based variable importance selection to identify the most effective modalities for differentiating whether a person has cLBP. The dataset included questionnaire data, clinical and functional assessments, and spino-pelvic magnetic resonance imaging (MRI), encompassing a total of 144 parameters from 1,161 adults with (n = 512) and without cLBP (n = 649). Boruta and random forest were utilised for variable importance selection and cLBP classification respectively. A multimodal model including questionnaire, clinical, and MRI data was the most effective in differentiating people with and without cLBP. From this, the most robust variables (n = 9) were psychosocial factors, neck and hip mobility, as well as lower lumbar disc herniation and degeneration. This finding persisted in an unseen holdout dataset. Beyond demonstrating the importance of a multi-dimensional approach to cLBP, our findings will guide the development of targeted diagnostics and personalized treatment strategies for cLBP patients.

Intra-Discal Vacuum phenomenon (IDVP) is associated with advanced disc degeneration, representing persistent intra-segmental movement. Our objective is to further characterise IDVP patterns from both MRI and CT thus informing on an otherwise poorly understood phenomenon.

An observational analysis was performed, including an over-60s population sample of 325 lumbar discs in 65 subjects (29 M, 36 F) with low back pain +/- leg symptoms, with MRI of the lumbar spine and concomitant CT abdomen. Exclusion criteria were those with insufficient quality, non-degenerative or destructive spinal pathology, previous neuromodulation or spine instrumentation.

49 subjects (94 levels) displayed IDVP, including 11/184 Pfirrmann grade 3/IVDP positive, 49/79 grade 4/IVDP positive and 34/39 grade 5/IVDP positive discs. Increased severity of IDVP significantly correlated with increased Pfirrmann grade and decreased disc height (p <.05). Affected IDVP levels within the L1L2 & L2L3 region when compared to the L4L5 & L5S1 region, displayed similar Pfirrmann grade (4.1 v 4.3) and disc height (0.52 v 0.51) but with greater severity of IDVP in the latter (1.5 v 1.98, p <.002). While 83/105 (81%) of levels with Pfirrmann 4/5 with reduced disc height, displayed IDVP, a small minority did not, where instead they displayed a significantly higher risk of adjacent IDVP (p <.05).

CT and MRI complement each other through the identification of IDVP, allowing the diagnostician further insight on disc degeneration. Worsening severity of IDVP on CT correlates with increased disc degeneration and reduced disc height on MRI, particularly in the lower lumbar spine. A small minority of advanced degenerate discs do not display IDVP and quiesce, mostly where there is presence of an adjacent IDVP.

Not applicable.

Pain in lower back is a common condition reported by astronauts, both during and after space missions. Investigating the alterations in the spine and the mechanisms driving these changes is essential for a deeper understanding of how microgravity impacts the human spine. This knowledge could also open pathways for therapeutic or preventive interventions. Nevertheless, there is a limited evidence regarding changes in intervertebral discs (IVDs) due to space travel.

In this study, 2 astronauts were enrolled in a space travel. Before the space flight, a lower back magnetic resonance imaging (MRI) scan was performed. We repeated an MRI instantly after 17-days space travel, and again 3 months after landing. The water content and glycosaminoglycan (GAGs) levels in the lumbar IVDs were evaluated using DIXON water-only phase imaging and T1rho MRI sequences. Additionally, alterations in the size and quality of the paraspinal muscles (PSMs), including fatty infiltration, were examined.

Varied alterations were observed in the IVDs and PSMs of both astronauts. One astronaut experienced a reduction in water and GAGs content, while the other showed an increase. These changes in the IVDs following spaceflight appeared to be linked to the degree of baseline degeneration. Regarding the PSMs, differences in size and fatty infiltration also varied between the two astronauts. Notably, these changes had not stabilized by the final follow-up at 3 months.

Our findings offer initial evidence indicating that even brief exposures to microgravity might be linked to biochemical alterations in IVDs and changes in the quality of PSMs, which could continue evolving for more than 3 months after returning from space.

Degenerative changes in the lumbar spine may affect many structures, among them the intervertebral discs and the facet joints. The individual load distribution within the spine linked to posture and mass distribution is a probable cause of disease. This study had a dual aim: first, to systematically summarize previously reported associations between sagittal balance parameters and the occurrence of lumbar spine degeneration. Second, to complement these insights with additional biomechanical findings meant to elucidate the link between spine load and alignment as well as selected demographic descriptors.

A systematic literature search was performed on PubMed to identify clinical studies that quantified the association between spinal alignment and the occurrence of disc herniation, disc degeneration, facet joint degeneration, and spondylolisthesis. Further, a previously published musculoskeletal model was used to link sagittal spinal alignment and subject characteristics to joint loading within the lumbar spine for a cohort of 144 subjects.

The literature review yielded 49 publications evaluating the relationship between spinal alignment and the occurrence of pathologies in the lumbar spine. The results indicate that a straight spine might negatively affect the health status of the intervertebral disc, likely because of a lack of damping and associated high compressive loads. These loads further show a major dependence on body weight. On the other hand, facet degeneration and spondylolisthesis may be linked to higher anterior-posterior shear forces acting on the relevant spinal structures because of a generally more sagittally curved spine. A straight lumbar spine is more likely to stress the disc, whereas highly curved spines with a high pelvic incidence are more likely to stress the posterior structures. The biggest influencing factors on the resulting force and consequently potentially the wear of the anatomical structures are the intervertebral inclination from an anatomical point of view and the weight from a demographic point of view.

Information concerning spinal loading resulting from spinal alignment and body descriptors could impact both conservative treatment and operative planning for patients afflicted by spine disease through targeted changes in posture.

Percutaneous transforaminal endoscopic decompression (PTED) is widely used for treating lumbar spinal stenosis (LSS), yet predictors of reoperation remain unclear. This study aimed to explore the association between spinopelvic alignment and the reoperation following PTED.

A 1:2 matched case-control study was conducted, involving patients who underwent single-level PTED for LSS at our institution from May 2014 to August 2022. Cases comprised patients requiring reoperation after initial PTED, while controls were those without reoperation during the follow-up. Measured radiological parameters included pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), mismatch between pelvic incidence and lumbar lordosis (PI-LL), disc height (DH), Pfirrmann classification, and Modic changes (MCs). Univariate and multivariate logistic regression analyses were performed to identify predictors. Receiver operating characteristic (ROC) curves were generated to determine cut-off points.

76 cases and 152 controls were selected from 1967 enrolled patients. Both groups had an average age of 61 years, a male-to-female ratio of 43:33, and a mean BMI of 25.95 kg/m². No significant differences in baseline characteristics were found between groups. Multivariate analysis identified PT (OR = 1.061, P = 0.007), PI-LL (OR = 1.057, P = 0.021), and DH (OR = 1.194, P = 0.015) as independent risk factors for the reoperation. ROC analysis revealed PI-LL with an area under the curve (AUC) of 0.662 at a cut-off of 12.95° (95% CI = 0.582-0.741), PT with an AUC of 0.685 at a cut-off of 21.98° (95% CI = 0.606-0.763), and DH with an AUC of 0.602 at a cut-off of 8.22° (95% CI = 0.521-0.683).

PI-LL ≥ 12.95°, PT ≥ 21.98°, and DH ≥ 8.22° are independent risk factors for reoperation following PTED.

Degenerative spondylolisthesis (DS) is addressed with a wide range of surgical techniques, though controversy exists regarding surgical technique selection. Given the lack of high-quality evidence to guide surgical technique selection in DS, appropriateness criteria and classification systems have been developed based on expert opinion. The DSIC System uses imaging and patient characteristics to predict stability. The purpose of this study was to evaluate the DSIC system as a guide for technique selection by determining if patients within each DSIC Type have different outcomes when treated with various surgical techniques.

Patients undergoing surgery for symptomatic DS were prospectively enrolled at two centers. All patients were classified by DSIC Type and surgical technique. Due to small numbers in some subgroups, decompression alone and decompression with uninstrumented fusion were combined as uninstrumented group and decompression with instrumented and circumferential fusion were combined as instrumented group. The primary outcome was the 12-month change on the Core Outcome Measures Index (COMI).

Of the 508 patients enrolled, 459 patients could be classified according to DSIC criteria. 10 patients were classified as DSIC Type I (stable), 366 as DSIC Type II (potentially unstable), and 83 as DSIC Type III (unstable). Surgical technique varied significantly across DSIC Type, with decompression alone performed most commonly in DSIC I and decompression and fusion performed more commonly in DSIC II and III. There were no significant differences in COMI scores between the DSIC groups at baseline, 3 or 12 months post-operatively. At 12 months, the DSIC I uninstrumented group improved by 3.48 points on the COMI compared to 1.75 points in the DSIC I instrumented group (p > 0.05). The DSIC III uninstrumented group improved by 2.94 points at 12 months compared to the DSIC III instrumented group that improved by 4.06 points (p > 0.05). DSIC II patients showed similar COMI score improvement between the surgical technique groups. All DSIC groups improved significantly from baseline with greater than 75% of patients meeting minimal clinically important difference. Patients in DSIC I trended toward greater improvement with decompression alone, and patients in DSIC III trended toward greater improvement with decompression and instrumented fusion. There were no significant differences in reoperation rates between surgical technique cohorts.

This study found no significant differences in COMI scores between the surgical technique cohorts within each DSIC Type. There were non-significant trends suggesting that DSIC III patients with unstable slips may benefit from instrumented fusion, whereas DSIC I patients with stable slips may improve more with decompression alone or with an uninstrumented fusion. This study does not support the use of the DSIC for surgical technique selection and suggests that more work is needed to develop an evidence-based classification system that can guide surgical technique selection.

Intervertebral disc degeneration (IDD) continues to be a major health concern. The combination of Bajitian and Niuxi (B&N) is commonly used to treat musculoskeletal degenerative diseases. This study aimed to explore the potential of B&N in treating IDD through in vivo experiments and bioinformatics approaches. In vivo experiments found that the process of IDD in rats treated with B&N extracts was delayed. Through database screening and network pharmacology analysis, it was discovered that multiple key drug-active ingredients (DAIs) of B&N, such as wogonin, baicalein, 1-hydroxy-3-methoxy-9,10-anthraquinone, and beta-sitosterol, might play a role in the treatment of IDD, among which signaling pathways, such as PI3K-AKT, MAPK, and senescence signaling, might be the main drug-regulated pathways. The binding potential and position of the main DAIs to the core targets were verified by structural bioinformatics. Immunohistochemistry and qRT-PCR results indicated that B&N treatment could improve the expressions of Type II collagen (Col-2) and aggrecan (ACAN) in IDD rats, which might be related to the phosphorylation levels of AKT and p38. Therefore, the B&N formula might delay IDD in rats by regulating multiple signaling pathways through DAIs, which provides new approaches for further exploring the prevention and treatment strategies of IDD with traditional Chinese medicine.

Aging is a pivotal risk factor for intervertebral disc degeneration (IVDD) and chronic low back pain (LBP). The restoration of aging nucleus pulposus cells (NPCs) to a youthful epigenetic state is crucial for IVDD treatment, but remains a formidable challenge. Here, we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes (Oct4, Klf4 and Sox2) in Cavin2-modified exosomes (OKS@M-Exo) for treatment of IVDD and alleviating LBP. The functional OKS@M-Exo efficaciously alleviated senescence markers (p16INK4a, p21CIP1 and p53), reduced DNA damage and H4K20me3 expression, as well as restored proliferation ability and metabolic balance in senescent NPCs, as validated through in vitro experiments. In a rat model of IVDD, OKS@M-Exo maintained intervertebral disc height, nucleus pulposus hydration and tissue structure, effectively ameliorated IVDD via decreasing the senescence markers. Additionally, OKS@M-Exo reduced nociceptive behavior and downregulated nociception markers, indicating its efficiency in alleviating LBP. The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation. Collectively, reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.

Degenerative disc disease (DDD) is a common spinal condition characterized by the deterioration of intervertebral discs, leading to chronic back pain and reduced mobility. While magnetic resonance imaging (MRI) has long been the standard for late-stage DDD diagnosis, its limitations in early-stage detection prompt the exploration of advanced imaging methods. Positron emission tomography/computed tomography (PET/CT) using 18F- fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) has shown promise in identifying metabolic imbalances and age-related spinal degeneration, thereby complementing CT grading of the disease. The novel hybrid imaging modality PET/MRI provides new opportunities and are briefly discussed. The complex pathophysiology of DDD is dissected to highlight the role of genetic predisposition and lifestyle factors such as smoking and obesity. These etiological factors significantly impact the lumbosacral region, manifesting in chronic low back pain (LBP) and potential nerve compression. Traditional grading systems, like the Pfirrmann classification for MRI, are evaluated for their limitations in capturing the full spectrum of DDD. The potential to identify early disease processes and predict patient outcomes by the use of artificial intelligence (AI) is also briefly mentioned. Overall, the manuscript aims to spotlight advancements in imaging technologies for DDD, emphasizing their implications in refining both diagnosis and treatment strategies. The role of ongoing and future research is emphasized to validate these emerging techniques and overcome current limitations for more effective early detection and treatment.