Biomechanical analysis of adjacent segments after correction surgery for adult idiopathic scoliosis: a finite element analysis.

The biomechanical aspects of adjacent segment degeneration after Adult Idiopathic Scoliosis (AdIS) corrective surgery involving postoperative changes in motion and stress of adjacent segments have yet to be investigated. The objective of this study was to evaluate the biomechanical effects of corrective surgery on adjacent segments in adult idiopathic scoliosis by finite element analysis. Based on computed tomography data of the consecutive spine from T1-S1 of a 28-year-old male patient with adult idiopathic scoliosis, a three-dimensional finite element model was established to simulate the biomechanics. Two posterior long-segment fixation and fusion operations were designed: Strategy A, pedicle screws implanted in all segments of both sides, and Strategy B, alternate screws instrumentation on both sides. The range of motion (ROM), Maximum von Mises stress value of intervertebral disc (IVD), and Maximum von Mises stress of the facet joint (FJ) at the fixation adjacent segment were calculated and compared with data of the preoperative AdIS model. Corrective surgery decreased the IVD on the adjacent segments, increased the FJ on the adjacent segments, and decreased the ROM of the adjacent segments. A greater decrease of Maximum von Mises stress was observed on the distal adjacent segment compared with the proximal adjacent segment. The decrease of Maximum von Mises stress and increment of Maximum von Mises stress on adjacent FJ in strategy B was greater than that in strategy A. Under the six operation modes, the change of the Maximum von Mises stress on the adjacent IVD and FJ was significant. The decrease in ROM in the proximal adjacent segment was greater than that of the distal adjacent segment, and the decrease of ROM in strategy A was greater than that in strategy B. This study clarified the biomechanical characteristics of adjacent segments after AdIS corrective surgery, and further biomechanical analysis of two different posterior pedicle screw placement schemes by finite element method. Our study provides a theoretical basis for the pathogenesis, prevention, and treatment of adjacent segment degeneration after corrective surgery for AdIS.

Enzymatic denaturation versus excessive fatigue loading degeneration: Effects on the time-dependent response of the intervertebral disc.

Degenerative disc disease (DDD), regardless of its phenotype and clinical grade, is widely associated with low back pain (LBP), which remains the single leading cause of disability worldwide. This work provides a quantitative methodology for comparatively investigating artificial IVD degeneration via two popular approaches: enzymatic denaturation and fatigue loading. An in-vitro animal study was used to study the time-dependent responses of forty fresh juvenile porcine thoracic IVDs in conjunction with inverse and forward finite element (FE) simulations. The IVDs were dissected from 6-month-old-juvenile pigs and equally assigned to 5 groups (intact, denatured, low-level, medium-level, high-level fatigue loading). Upon preloading, a sinusoid cyclic load (Peak-to-peak/0.1-to-0.8 MPa) was applied (0.01-10 Hz), and dynamic-mechanical-analyses (DMA) was performed. The DMA outcomes were integrated with a robust meta-model analysis to quantify the poroelastic IVD characteristics, while specimen-specific FE models were developed to study the detailed responses. The results demonstrated that enzymatic denaturation had a more significantly pronounced effect on the resistive strength and shock attenuation capabilities of the intervertebral discs. This can be attributed to the simultaneous disruption of the collagen fibers and water-proteoglycan bonds induced by trypsin digestion. Fatigue loading, on the other hand, primarily influenced the disc's resistance to deformation in a frequency-dependent pattern, where alterations were most noticeable at low loading frequencies. This study confirms the intricate interplay between the biochemical changes induced by enzymatic processes and the mechanical behavior stemming from fatigue loading, suggesting the need for a comprehensive approach to closely mimic the interrelated multifaceted processes of human disc degeneration.

Biomechanical analysis of single and multi-level artificial disc replacement (ADR) in cervical spine using multi-scale loadings: A finite element study.

Artificial disc replacement (ADR) is a clinical procedure used to diagnose cervical degenerative disc disease, preserving range of motion (ROM) at the fixation level and preventing adjacent segment degeneration (ASD). This study analyzed the biomechanics of ADR by examining range of motion (ROM), stress levels in bone and implants, and strain in the bone-implant interface using multi-scale loadings. The study focused on single- and double-level patients across various loading scales during physiological motions within the cervical spine. Results showed increased ROM in single-level and double-level fixations during physiological loadings, while ROM decreased at the adjacent level of fixation with the intact cervical spine model. The Prodisc-Implant metal endplate experienced a maximum von Mises stress of 432 MPa during axial rotation, confirming the long durability and biomechanical performance of the bone-implant interface.

Biomechanical investigation of a customized interspinous spacer system in the treatment of degenerative disc diseases: A finite element analysis.

BACKGROUND: A novel interspinous fixation system based on anatomical parameters and incorporating transfacetopedicular screws, was developed to treat degenerative disc diseases. The biomechanical characteristics of the novel system were evaluated using finite element analysis in comparison to other classical interspinous spacers. METHODS: The L1-S1 lumbar spine finite element models were surgically implanted with the novel system, Coflex and DIAM devices at the L4/L5 segment to assess the range of motion, the pression distribution of intervertebral disc, the peak stresses on the spinous process and implant during various motions. FINDINGS: Range of motions of the L4/L5 surgical segment were reduced by 29.13%, 61.27%, 77.35%, 33.33%, and the peak stresses of intervertebral disc were decreased by 36.82%, 67.31%, 73.00%, 69.57% for the novel system in flexion, extension, lateral bending, and axial rotation when compared with the Coflex, and they were declined by 34.53%, 57.86%, 75.81%, 25.21%; 36.22%, 67.31%, 75.01%, 71.40% compared with DIAM. The maximum stresses of the spinous process were 29.93 MPa, 24.66 MPa, 14.45 MPa, 24.37 MPa in the novel system, and those of Coflex and DIAM were 165.3 MPa, 109 MPa, 84.79 MPa, 47.66 MPa and 52.59 MPa, 48.78 MPa, 50.27 MPa, 44.16 MPa during the same condition. INTERPRETATION: Compared to other interspinous spacer devices, the novel interspinous fixation system demonstrated excellent stability, effectively distributing load on the intervertebral disc, and reducing the risk of spinous process fractures. The personalized design of the novel interspinous fixation system could be a viable option for treating degenerative disc diseases.

Structural modification and biomechanical analysis of lumbar disc prosthesis: A finite element study.

BACKGROUND: Most ball-in-socket artificial lumbar disc implanted in the spine result in increased hypermobility of the operative level and overloading of the facet joint. METHODS: A finite element model was established and validated for the lumbar spine (L1-L5). The structure of the Mobidisc prosthesis was modified, resulting in the development of two new intervertebral disc prostheses, Movcore and Mcopro. The prostheses were implanted into the L3/L4 level to simulate total disc replacement, and the biomechanical properties of the lumbar spine model were analyzed after the operation. FINDINGS: Following the implantation of the prostheses, the mobility of operative level, peak stress of lumbar spine models, and peak stress of facet joint increased. The performance of mobility was found to be more similar between Movcore and Mobidisc. The mobility and facet joint peak stress of the Mcopro model decreased progressively with an increase in the Young's modulus of the artificial annulus during flexion, extension, and lateral bending. Among all the models, the Mcopro50 model had the mobility closest to the intact model. It showed a 3% decrease in flexion, equal range of motion in extension, a 9% increase in left lateral bending, a 7% increase in right lateral bending, and a 3% decrease in axial rotation. INTERPRETATION: The feasibility of the new intervertebral disc prostheses, Movcore and Mcopro, has been established. The Mcopro prosthesis, which features an artificial annular structure, offers significant advantages in terms of reduced mobility of the operative level and peak stress of facet joint.

On growth and scoliosis.

PURPOSE: To describe the physiology of spinal growth in patients with adolescent idiopathic scoliosis (AIS). METHODS: Narrative review of the literature with a focus on mechanisms of growth. RESULTS: In his landmark publication On Growth and Form, D'Arcy Thompson wrote that the anatomy of an organism reflects the forces it is subjected to. This means that mechanical forces underlie the shape of tissues, organs and organisms, whether healthy or diseased. AIS is called idiopathic because the underlying cause of the deformation is unknown, although many factors are  associated. Eventually, however, any deformity is due to mechanical forces. It has long been shown that the typical curvature and rotation of the scoliotic spine could result from vertebrae and intervertebral discs growing faster than the ligaments attached to them. This raises the question why in AIS the ligaments do not keep up with the speed of spinal growth. The spine of an AIS patient deviates from healthy spines in various ways. Growth is later but faster, resulting in higher vertebrae and intervertebral discs. Vertebral bone density is lower, which suggests  less spinal compression. This also preserves the notochordal cells and the swelling pressure in the nucleus pulposus. Less spinal compression is due to limited muscular activity, and low muscle mass indeed underlies the lower body mass index (BMI) in AIS patients. Thus, AIS spines grow faster because there is less spinal compression that counteracts the force of growth (Hueter-Volkmann Law). Ligaments consist of collagen fibres that grow by tension, fibrillar sliding and the remodelling of cross-links. Growth and remodelling are enhanced by dynamic loading and by hormones like estrogen. However, they are opposed by static loading. CONCLUSION: Increased spinal elongation and reduced ligamental growth result in differential strain and a vicious circle of scoliotic deformation. Recognising the physical and biological cues that contribute to differential growth  allows earlier diagnosis of AIS and prevention in children at risk.

Passive intervertebral restraint is different in patients with treatment-resistant chronic nonspecific low back pain: a retrospective cohort study and control comparison.

PURPOSE: In vivo studies of continuous lumbar sagittal plane motion have found passive intervertebral motion to be more uneven in patients with chronic nonspecific low back pain (CNSLBP) than healthy controls, but the mechanisms are unclear. This study aimed to compare patients with CNSLBP with a matched group of pain-free controls for intervertebral restraint during passive recumbent bending. METHODS: Seventeen patients with CNSLBP and minimal disc degeneration who had quantitative fluoroscopy investigations were matched to 17 healthy controls from a database acquired using the same imaging protocol. The entire database (n = 136) was examined for clustering of peaking times, magnitudes and ROM of the first derivatives of the intervertebral angle/motion curves (PTFD, PMFD and ROM) during flexion and return that might introduce confounding. The groups were then compared for differences in these variables. RESULTS: There were significant segmental ROM differences among clusters in the database when PMFD and ROM were used as clustering variables, indicating heterogeneity. However, in the patient-control study, it was PTFD (velocity) that differentiated the groups. At L5-S1, this was at 10.82% of the motion path compared with 25.06% in the controls (p = 0.0002). For L4-5, PTFD was at 23.42% of the motion path in patients and 16.33% in controls (p = 0.0694) suggesting a reduced initial bending moment there. There were no significant differences for PMFD or ROM. CONCLUSION: Peaking time of passive intervertebral velocity occurs early at L5-S1 in patients with CNSLBP; however, these findings should be treated with caution pending their replication. Future studies should explore relationships with altered disc pressures and biochemistry. Usefulness for monitoring regenerative disc therapies should be considered.

Biomechanical Comparison of Different Surgical Strategies for Skip-level Cervical Degenerative Disc Disease: A Finite Element Study.

STUDY DESIGN: We constructed finite element (FE) models of the cervical spine consisting of C2-C7 and predicted the biomechanical effects of different surgical procedures and instruments on adjacent segments, internal fixation systems, and the overall cervical spine through FE analysis. OBJECTIVE: To compare the biomechanical effects between the zero-profile device and cage-plate device in skip-level multistage anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: ACDF is often considered the standard treatment for degenerative cervical spondylosis. However, the selection of surgical methods and instruments in cases of skip-level cervical degenerative disk disease is still controversial. MATERIALS AND METHODS: Three FE models were constructed, which used noncontiguous 2-level Zero-P (NCZP) devices for C3/4 and C5/6, a noncontiguous 2-level cage-plate (NCCP) for C3/4 and C5/6, and a contiguous 3-level cage-plate (CCP) for C3/6. Simulate daily activities in ABAQUS. The range of motion (ROM), von Mises stress distribution of the endplate and internal fixation system, and intervertebral disk pressure (IDP) of each model were recorded and compared. RESULTS: Similar to the stress of the cortical bone, the maximum stress of the Zero-P device was higher than that of the CP device for most activities. The ROM increments of the superior, inferior, and intermediate segments of the NCZP model were lower than those of the NCCP and CCP models in many actions. In terms of the IDP, the increment value of stress for the NCZP model was the smallest, whereas those of the NCCP and CCP models were larger. Similarly, the increment value of stress on the endplate also shows the minimum in the NCZP model. CONCLUSIONS: Noncontiguous ACDF with zero profile can reduce the stress on adjacent intervertebral disks and endplates, resulting in a reduced risk of adjacent segment disease development. However, the high cortical bone stress caused by the Zero-P device may influence the risk of fractures.

Different Load-Induced Alterations in Intervertebral Discs Between Low Back Pain Patients and Controls: A T2-map Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Investigate load-induced effects in lumbar intervertebral discs (IVDs) and differences between low back pain (LBP) patients and controls. SUMMARY OF BACKGROUND DATA: T2-map values, obtained from quantitative MRI sequences, reflect IVD tissue composition and integrity. Feasibility studies with T2-mapping indicate different load-induced effects in entire IVDs and posterior IVD parts between LBP patients and controls. Larger studies are required to confirm these findings and increase the understanding of specific characteristics distinguishing IVD changes in LBP patients compared with controls. MATERIALS AND METHODS: Lumbar IVDs of 178 patients (mean age: 43.8 yr; range: 20-60 yr) with >3 months of LBP and 74 controls (mean age: 40.3 yr; range: 20-60 yr) were imaged with T2-map sequence in a 3T scanner in supine position without axial load, immediately followed by a repeated examination, using the same sequence, with axial load. On both examinations, mean T2-map values were obtained from entire IVDs and from central/posterior IVD parts on the three midsagittal slices in 855 patient IVDs and 366 control IVDs. Load-induced effect was compared with Fold-change ratio and adjusted for IVD-degeneration grade. RESULTS: Loading induced an increase in T2-map values in both patients and controls. Excluding most extreme values, the ranges varied between -15% and +35% in patients and -11% and +36% in controls (first to 99th percentile). Compared with controls, the T2-map value increase in patients was 2% smaller in entire IVDs (Fold-change: 0.98, P =0.031), and for central and posterior IVD parts 3% (Fold-change: 0.98, P =0.005), respectively, 2% (Fold-change: 0.9, P =0.015) smaller. CONCLUSIONS: This quantitative study confirmed diverse load-induced behaviors between LBP patients and controls, suggesting deviant biomechanical characteristics between IVDs in patients and controls not only attributed to the global grade of degeneration. These findings are an important step in the continuous work of identifying specific IVD phenotypes for LBP patients. LEVEL OF EVIDENCE: Level II.

Finite element analysis of a new preoperative traction for cervical kyphosis: suspensory traction.

A finite element model of cervical kyphosis was established to analyze the stress of cervical spine under suspensory traction and to explore the mechanism and effect of it. A patient with typical cervical kyphosis (C2-C5) underwent CT scan imaging, and 3D slicer was used to reconstruct the C2 to T2 vertebral bodies. The reconstructed data was imported into Hypermesh 2020 and Abaqus 2017 for meshing and finite element analysis. The changes of the kyphotic angle and the von Mises stress on the annulus fibrosus of each intervertebral disc and ligaments were analyzed under suspensory traction conditions. With the increase of suspensory traction weight, the overall kyphosis of cervical spine showed a decreasing trend. The correction of kyphosis was mainly contributed by the change of kyphotic segments. The kyphotic angle of C2-C5 was corrected from 45° to 13° finally. In cervical intervertebral discs, the stress was concentrated to anterior and posterior part, except for C4-5. The stress of the anterior longitudinal ligament (ALL) decreased from the rostral to the caudal, and the high level von Mises stress of the kyphotic segments appeared at C2-C3, C3-C4, and C4-C5. The roles of the other ligaments were not obvious. The kyphotic angle was significantly reduced by the suspensory traction. Shear effect due to the high von Mises stress in the anterior and posterior parts of annulus fibrosus and the tension on the anterior longitudinal ligament play a role in the correction of cervical kyphosis.

Evolving role of VIADISC for chronic low back and discogenic pain: a narrative review.

INTRODUCTION: Chronic lower back pain is a leading cause of disability and healthcare spending worldwide. Discogenic pain, pain originating from the intervertebral disk, is a common etiology of chronic lower back pain. Currently, accepted treatments for chronic discogenic pain focus only on the management of symptoms, such as pain. There are no approved treatments that stop or reverse degenerating intervertebral discs. Biologic therapies promoting disc regeneration have been developed to expand treatment options. VIADISC™ NP, is a viable disc allograft supplementation that, in a recent trial, demonstrated a significant reduction in pain and increased function in patients suffering from symptomatic degenerative disc disease. AREAS COVERED: This manuscript summarizes the epidemiology and etiology of low back pain, the pathophysiology of degenerative disc disease, current treatments, and a need for newer therapies. The rationale behind intradiscal biologics for the treatment of symptomatic degenerative disc disease is also discussed. EXPERT OPINION: Characterization of the biology leading to disc degeneration has allowed for the development of intradiscal biologics. They may soon be capable of preventing and reversing disc degeneration. Clinical trials have shown promise, but further research into efficacy and safety is needed before these therapies are widely employed.

Effect of patient-specific factors on regeneration in lumbar spine at healthy disc and total disc replacement. Computer simulation.

BACKGROUND AND OBJECTIVE: Degenerative diseases of the spine have a negative impact on the quality of life of patients. This study presents the results of numerical modelling of the mechanical behaviour of the lumbar spine with patient-specific conditions at physiological loads. This paper aims to numerically study the influence of degenerative changes in the spine and the presence of an endoprosthesis on the creation of conditions for tissue regeneration. METHODS: A numerical model of the mechanical behaviour of lumbar spine at healthy and after total disc replacement under low-energy impacts equivalent to physiological loads is presented. The model is based on the movable cellular automaton method (discrete elements), where the mechanical behaviour of bone tissue is described using the Biot poroelasticity accounting for the presence and transfer of interstitial biological fluid. The nutritional pathways of the intervertebral disc in cases of healthy and osteoporotic bone tissues were predicted based on the analysis of the simulation results according to the mechanobiological principles. RESULTS: Simulation of total disc replacement showed that osseointegration of the artificial disc plates occurs only in healthy bone tissue. With total disc replacement in a patient with osteoporosis, there is an area of increased risk of bone resorption in the near-contact area, approximately 1 mm wide, around the fixators. Dynamic loads may improve the osseointegration of the implant in pathological conditions of the bone tissue. CONCLUSIONS: The results obtained in the case of healthy spine and osteoporotic bone tissues correspond to the experimental data on biomechanics and possible methods of IVD regeneration from the position of mechanobiological principles. The results obtained with an artificial disc (with keel-type fixation) showed that the use of this type of endoprosthesis in healthy bone tissues allows to reproduce the function of the natural intervertebral disc and does not contribute to the development of neoplastic processes. In the case of an artificial disc with osteoporosis of bone tissues, there is a zone with increased risk of tissue resorption and development of neoplastic processes in the area near the contact of the implant attachment. This circumstance can be compensated by increasing the loading level.

Update on the Correlation Between Mitochondrial Dysfunction and Intervertebral Disk Degeneration.

Low back pain (LBP) is a common disorder in orthopedic outpatients, affecting people of all ages, and some patients may develop chronic LBP. As a complex organelle, mitochondria are not only energy workstations but also regulate cell senescence, apoptosis, and homeostasis. Mitochondrial dysfunction promotes disk degeneration by affecting a variety of pathophysiological processes, including oxidative stress, mitophagy, mitochondrial homeostasis, cellular senescence, and cell death. We review the molecular mechanisms underlying the relationship between mitochondrial dysfunction and intervertebral disk degeneration (IDD) to provide a theoretical basis for IDD treatment using pharmacological or tissue-engineering approaches.

The Mechanism and Function of miRNA in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) disease has been considered as the main cause of low back pain (LBP), which is a very common symptom and the leading cause of disability worldwide today. The pathological mechanism of IDD remains quite complicated, and genetic, developmental, biochemical, and biomechanical factors all contribute to the development of the disease. There exists no effective, non-surgical treatment for IDD nowadays, which is largely related to the lack of knowledge of the specific mechanisms of IDD, and the lack of effective specific targets. Recently, non-coding RNA, including miRNA, has been recognized as an important regulator of gene expression. Current studies on the effects of miRNA in IDD have confirmed that a variety of miRNAs play a crucial role in the process of IDD via nucleus pulposus cells (NPC) apoptosis, abnormal proliferation, inflammatory factors, the extracellular matrix (ECM) degradation, and annulus fibrosus (AF) degeneration. In the past 10 years, research on miRNA has been quite active in IDD. This review summarizes the current research progression of miRNA in the IDD and puts forward some prospects and challenges on non-surgical treatment for IDD.

Does discectomy improve low back pain as well as radiating pain in patients with lumbar herniated intervertebral disc (HIVD)?

ABSTRACT: Most postoperative patients with herniated lumbar disc complained of lower leg radiating pain (LRP), referred buttock pain (RBP), and low back pain (LBP). When discectomy is performed, improvement in LRP is observed due to spinal nerve irritation. However, long-term LBP due to degenerative changes in the disc may occur postoperatively. In addition, limited research has been reported on the short-term (within 1 year) improvement in LBP after discectomy. This study aimed to evaluate the effectiveness of discectomy in reducing LBP within 1 year postoperatively.Among the 183 patients who underwent discectomy performed by a single surgeon from January 2010 to December 2016, 106 who met the inclusion and exclusion criteria were enrolled. In the 106 patients who underwent lumbar discectomy, 3 types of spine-related pain were pre-operatively assessed and 3, 6, and 12 months postoperatively. Functional outcomes were evaluated, and quality of life was assessed 12 months postoperatively by using the Short-Form 36 questionnaire, which was subdivided into mental and physical components.LBP showed both statistical and clinical improvement within the first 3 months postoperatively, but the improvement was not observed until 12 months postoperatively. RBP and LRP showed both statistical and clinical improvement within the first 3 months and further consistently showed statistical improvement. LBP improved clinically only until 3 months postoperatively regardless of the type of herniation.LBP showed improvement within the first 3 months postoperatively and plateaued afterward, and RBP and radiculopathy showed consistent improvement until 12 months postoperatively. This may explain why patients from 12-month follow-up showed improvement in RBP and radiculopathy but not LBP.

The Effects of Elgucare on Degenerated Intervertebral Disc-Induced Low Back Pain and Disc Regeneration: A Clinical Trial.

INTRODUCTION: Chronic low back pain (LBP) has a wide range of causes. However, most cases are induced by degeneration of the lumbar intervertebral discs (IVDs), and the aching caused by local compression of the affected region has considerable impacts on quality of life. This clinical trial investigated the use of Elgucare, a Chinese herbal formula, as a food supplement to reduce the pain of patients with LBP induced by degeneration of the lumbar IVDs. METHODS: The study assessed patient subjective quality of life, functional limitations caused by LBP, and variations in pain. The assessment was done through the visual analogue scale (VAS) and effects on lumbar IVD thickness, water content, and bone mineral density (BMD). These parameters were evaluated before and after the administration of Elgucare or a placebo, one of which was taken by each participant for a 12-month period. RESULTS: Elgucare reduced the patients' mean VAS pain score by 2.25 points and improved their mean LBP-hampered mobility as assessed by the Roland-Morris Questionnaire by 5.17 points. The results of another questionnaire indicated that Elgucare slowed the LBP-induced deterioration of patients' quality of life, while objective assessment indices obtained through X-ray and magnetic resonance imaging showed that the height and water retention of their IVDs were increased. However, the BMD results showed no improvements. CONCLUSIONS: Elgucare can increase the water retention and height of IVDs and reduce LBP, thereby enhancing quality of life. Therefore, Elgucare can potentially be used as a clinical supplement.

MAPK /ERK signaling pathway: A potential target for the treatment of intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degenerative disease, which is considered the main cause of low back pain. It seriously affects the quality of life of patients and consequently brings a heavy economic burden to their families and the society. Although IDD is considered a natural process in degenerative lesions, it is mainly caused by aging, trauma, genetic susceptibility and other factors. It is closely related to changes in the tissue structure and function, including the progressive destruction of extracellular matrix, cell aging, cell death of the intervertebral disc (IVD), inflammation, and impairment of tissue biomechanical function. Currently, the treatment of IDD is aimed at alleviating symptoms rather than at targeting pathological changes in the IVD. Furthermore, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway is closely related to various pathological processes in IDD, and the activation of the MAPK/ERK pathway promotes the degradation of the IVD extracellular matrix, cell aging, apoptosis, and inflammatory responses. It also induces autophagy and oxidative stress that accelerate the IVD process. In our current review, we summarize the latest developments in the negative regulation of IDD after activation of the MAPK/ERK signaling pathway and emphasize on its influence on IDD. Targeting this pathway may become an attractive treatment strategy for IDD in the near future.

Stem Cells and Exosomes: New Therapies for Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) occurs as a result of an imbalance of the anabolic and catabolic processes in the intervertebral disc, leading to an alteration in the composition of the extracellular matrix (ECM), loss of nucleus pulposus (NP) cells, excessive oxidative stress and inflammation. Degeneration of the IVD occurs naturally with age, but mechanical trauma, lifestyle factors and certain genetic abnormalities can increase the likelihood of symptomatic disease progression. IVDD, often referred to as degenerative disc disease (DDD), poses an increasingly substantial financial burden due to the aging population and increasing incidence of obesity in the United States. Current treatments for IVDD include pharmacological and surgical interventions, but these lack the ability to stop the progression of disease and restore the functionality of the IVD. Biological therapies have been evaluated but show varying degrees of efficacy in reversing disc degeneration long-term. Stem cell-based therapies have shown promising results in the regeneration of the IVD, but face both biological and ethical limitations. Exosomes play an important role in intercellular communication, and stem cell-derived exosomes have been shown to maintain the therapeutic benefit of their origin cells without the associated risks. This review highlights the current state of research on the use of stem-cell derived exosomes in the treatment of IVDD.

DNMT3B decreases extracellular matrix degradation and alleviates intervertebral disc degeneration through TRPA1 methylation to inhibit the COX2/YAP axis.

Intervertebral disc degeneration (IVDD) is a main cause of low back pain that is associated with extracellular matrix (ECM) degradation and inflammation. This study aims to investigate the role of DNMT3B and its regulatory mechanisms in IVDD. IVDD rat models were constructed followed by transfections with oe-DNMT3B or oe-YAP in order to explore the role of DNMT3B in the development of IVDD. After that transfection, nucleus pulposus (NP) cells were isolated and transfected with oe-DNMT3B, oe-TRPA1, si-YAP, oe-YAP or oe-COX2 in order to investigate the functions of DNMT3B in NP cells. DNMT3B was poorly expressed in IVDD tissues and NP cells whereas TRPA1, COX2, and YAP were highly expressed. The proliferation or apoptosis of NP cells was detected through CCK-8 assay or flow cytometry, respectively. Overexpression of DNMT3B promoted the proliferation of NP cells, inhibited their apoptosis, as well as increasing the expression of collagen II and aggrecan and decreasing expression of MMP3 and MMP9. Besides, DNMT3B suppressed inflammation and alleviated IVDD. Mechanistically, DNMT3B modified the TRPA1 promoter by methylation to inhibit the expression of COX2. Overexpression of COX2 promoted the apoptosis of NP cells and decreased the expression of YAP, which was reversed by upregulating DNMT3B. DNMT3B may promote the proliferation of NP cells and prevent their ECM degradation through the TRPA1/COX2/YAP axis, thereby alleviating IVDD in rats.

The biomechanical effect on the adjacent L4/L5 segment of S1 superior facet arthroplasty: a finite element analysis for the male spine.

BACKGROUND: The superior facet arthroplasty is important for intervertebral foramen microscopy. To our knowledge, there is no study about the postoperative biomechanics of adjacent L4/L5 segments after different methods of S1 superior facet arthroplasty. To evaluate the effect of S1 superior facet arthroplasty on lumbar range of motion and disc stress of adjacent segment (L4/L5) under the intervertebral foraminoplasty. METHODS: Eight finite element models (FEMs) of lumbosacral vertebrae (L4/S) had been established and validated. The S1 superior facet arthroplasty was simulated with different methods. Then, the models were imported into Nastran software after optimization; 500 N preload was imposed on the L4 superior endplate, and 10 N⋅m was given to simulate flexion, extension, lateral flexion and rotation. The range of motion (ROM) and intervertebral disc stress of the L4-L5 spine were recorded. RESULTS: The ROM and disc stress of L4/L5 increased with the increasing of the proportions of S1 superior facet arthroplasty. Compared with the normal model, the ROM of L4/L5 significantly increased in most directions of motion when S1 superior facet formed greater than 3/5 from the ventral to the dorsal or 2/5 from the apex to the base. The disc stress of L4/L5 significantly increased in most directions of motion when S1 superior facet formed greater than 3/5 from the ventral to the dorsal or 1/5 from the apex to the base. CONCLUSION: In this study, the ROM and disc stress of L4/L5 were affected by the unilateral S1 superior facet arthroplasty. It is suggested that the forming range from the ventral to the dorsal should be less than 3/5 of the S1 upper facet joint. It is not recommended to form from apex to base. LEVEL OF EVIDENCE: Level IV.