Disc Cells Research Articles

The physiological, in-vitro simulation of daily activities in the intervertebral disc using a load Informed kinematic evaluation (LIKE) protocol

Current spinal testing protocols generally adopt pure moments combined with axial compression. However, daily activities involve multi-axis loads, and multi-axis loading has been shown to impact intervertebral disc (IVD) cell viability. Therefore, integrating in-vivo load data with spine simulators is critical to understand how loading affects the IVD, but doing so is challenging due to load coupling and variable load rates. This study addresses these challenges through the Load Informed Kinematic Evaluation (LIKE) protocol, which was evaluated using the root mean squared error (RMSE) between desired and actual loads in each axis. Stage 1 involves obtaining the kinematics from six-axis load control tests replicating 20 Orthoload activities at a reduced test speed. Stage 2 applies these kinematics in five axes, with axial compression applied in load control, at the reduced speed and at the physiological test rate. Stage 3 enables long-term tests through six-axis kinematic control combined with diurnal height correction to account for the natural height fluctuations of the IVD. Stage 1 yielded RMSEs within twice the load cell noise floor. Low RMSEs were maintained during stage 2 at reduced speed (Tx:0.80 ± 0.30 N; Ty:0.77 ± 0.29 N; Tz:1.79 ± 0.50 N; Rx:0.02 ± 0.01Nm; Ry:0.02 ± 0.01Nm; and Rz:0.02 ± 0.01Nm) and at the physiological test rate (Tx:3.45 ± 1.81 N; Ty:3.82 ± 1.99 N; Tz:11.32 ± 8.69 N; Rx:0.13 ± 0.07Nm; Ry:0.16 ± 0.11Nm; and Rz:0.07 ± 0.04Nm). To address unwanted oscillations observed in longer tests (>2h), Stage 3 was introduced to enable the stable and consistent replication of activities at a physiological test rate. Despite higher RMSEs the axial error was 85.5 ± 24.27 N (equivalent to ∼ 0.16 MPa), with shear RMSEs similar to other testing systems conducting pure moment tests at slower rates. The LIKE protocol enables the replication of physiological loads, providing opportunities for enhanced investigations of IVD mechanobiology, and the pre-clinical evaluation of IVD devices and therapies.

Effect of osmoregulatory on the secondary somatic embryogenesis of cocoa (Theobroma cacao L.)

Cocoa (Theobroma cacao L.) is the raw material for the worldwide chocolate industry. To ensure high quality and efficient field production, the industry relies on a uniformity of elite cocoa plants, which can be achieved through vegetative propagation methods like somatic embryogenesis. However, the low yield rate in the multiplication and regeneration of cocoa plants remains a challenge for basic research. To obtain a greater number of secondary somatic embryos (SSE) in cocoa, the effect of three osmoregulators on the disc cells of primary somatic embryos (PSE) of cocoa was studied. PSE was induced from cocoa staminodes of genotype I52. Epicotyls were selected from PSE at the torpedo and cotyledon stages, segmented into 3 mm discs, and placed in a secondary callus growth medium. The explants were transferred to embryo development medium 3, where they were exposed to the osmoregulatory polyethylene glycol (PEG), mannitol, and sorbitol at the following concentrations: 0%, 1%, 3%, and 5%. D-Mannitol at 3% and D-Sorbitol at 1% increased the number of SSE at the torpedo, globular, and cotyledon stage per explant. The culture medium with 1% PEG significantly increased the formation of SSE in the globular and cotyledonal stages. The results presented a positive effect of the osmoregulators on the formation of cocoa SSE.

An innovative tunable bimodal porous PCL/gelatin dressing fabricated by electrospinning and 3D printing for efficient wound healing and scalable production

This study presents the development of tunable scaffolds with bimodal porosity comprising poly(ε-caprolactone) (PCL) micro-meshes and PCL/gelatin/ε-polylysine (ε-PL) fibrous layers. Pure PCL scaffolds were prepared using the fused deposition modeling technique featuring grid geometry and interconnected micro-pores, followed by electrospinning to produce PCL/gelatin/ε-PL nanofibrous layers. Field emission scanning electron microscopy was employed to investigate the morphological features of the scaffolds, while the physicomechanical properties were studied using tensile and contact angle tests. Antibacterial performance and skin cell toxicity of the scaffolds were determined by bacterial disc diffusion and cell viability assays, respectively. Morphological analysis showed the presence of micro-to nano-sized pores in the developed scaffolds. The mechanical test results revealed that the prepared scaffolds exhibited Young's modulus values similar to the human skin with higher strain. The nanocomposite scaffolds were cytocompatible and effectively eradicated common bacteria associated with cutaneous wounds. In light of the aforementioned results along with facile fabrication, the tunable PCL/gelatin/ε-PL porous scaffolds hold great promise for applications in skin wound repair.

In vitro differentiation of human induced pluripotent stem cells into temporomandibular joint disc like cells

Temporomandibular joint discs (TMJ discs) are unable to repair themselves in disease states, while induced stem cell differentiation is a common method to repair tissue defects. Nowadays, kinds of stem cells are attempted for tissue regeneration of TMJ disc, but these methods have several downsides, which limit their wide application. The proliferation and differentiation ability of human induced pluripotent stem cells (hiPSC) provides a new research direction for TMJ disc tissue regeneration. In this study, we investigated the feasibility of induced differentiation of hiPSC into TMJ disc cells in vitro and the differentiation efficiency of different methods to clarify the possibility and conditions of hiPSC application in TMJ disc tissue engineering. We collected sheep TMJ disc cells cultures for adding in hiPSC culture environment and treated hiPSC by both direct induction and Transwell co-culture for 7 days, 14 days and 21 days. The secretion of extracellular matrix in TMJ disc cells was detected by Sirius Red and Safranin O staining. Collagen Ⅰ and Collagen Ⅱ were qualitatively detected by immunohistochemical staining. The expression of extracellular matrix genes (type I collagen (COL1A1), type II collagen(COL2), glycosaminoglycan (GAG)), chondrogenic differentiation gene SOX9 and pluripotency gene OCT4 were detected by RT-qPCR. Our results showed that hiPSC had the ability to differentiate to TMJ disc cells by direct induction in TMJ disc cell culture medium and by Transwell co-culture method. The highest degree of differentiation was observed after 14 days of direct induction, while Transwell co-culture showed significant differentiation at different times and with different major directions. Meanwhile, Transwell co-culture not only differentiates hiPSC but also promotes the growth and proliferation of TMJ disc cells. Our study is valuable to investigate the possibility of differentiation of hiPSC toward TMJ disc cells and to determine the time of differentiation. It provides new ideas for the selection of seed cells for TMJ disc tissue engineering.

Diagnostic model based on key autophagy-related genes in intervertebral disc degeneration

BackgroundCurrent research on autophagy is mainly focused on intervertebral disc tissues and cells, while there is few on human peripheral blood sample. therefore, this study constructed a diagnostic model to identify autophagy-related markers of intervertebral disc degeneration (IVDD).MethodsGSE150408 and GSE124272 datasets were acquired from the Gene Expression Omnibus database, and differential expression analysis was performed. The IVDD-autophagy genes were obtained using Weighted Gene Coexpression Network Analysis, and a diagnostic model was constructed and validated, followed by Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Meanwhile, miRNA–gene and transcription factor–gene interaction networks were constructed. In addition, drug-gene interactions and target genes of methylprednisolone and glucosamine were analyzed.ResultsA total of 1,776 differentially expressed genes were identified between IVDD and control samples, and the composition of the four immune cell types was significantly different between the IVDD and control samples. The Meturquoise and Mebrown modules were significantly related to immune cells, with significant differences between the control and IVDD samples. A diagnostic model was constructed using five key IVDD-autophagy genes. The area under the curve values of the model in the training and validation datasets were 0.907 and 0.984, respectively. The enrichment scores of the two pathways were significantly different between the IVDD and healthy groups. Eight pathways in the IVDD and healthy groups had significant differences. A total of 16 miRNAs and 3 transcription factors were predicted to be of great value. In total, 84 significantly related drugs were screened for five key IVDD-autophagy genes in the diagnostic model, and three common autophagy-related target genes of methylprednisolone and glucosamine were predicted.ConclusionThis study constructs a reliable autophagy-related diagnostic model that is strongly related to the immune microenvironment of IVD. Autophagy-related genes, including PHF23, RAB24, STAT3, TOMM5, and DNAJB9, may participate in IVDD pathogenesis. In addition, methylprednisolone and glucosamine may exert therapeutic effects on IVDD by targeting CTSD, VEGFA, and BAX genes through apoptosis, as well as the sphingolipid and AGE-RAGE signaling pathways in diabetic complications.

Roles of Chemokines in Intervertebral Disk Degeneration.

Intervertebral disc degeneration is the primary etiology of low back pain and radicular pain. This review examines the roles of crucial chemokines in different stages of degenerative disc disease, along with interventions targeting chemokine function to mitigate disc degeneration. The release of chemokines from degenerated discs facilitates the infiltration and activation of immune cells, thereby intensifying the inflammatory cascade response. The migration of immune cells into the venous lumen is concomitant with the emergence of microvascular tissue and nerve fibers. Furthermore, the presence of neurogenic factors secreted by disc cells and immune cells stimulates the activation of pain-related cation channels in the dorsal root ganglion, potentially exacerbating discogenic and neurogenic pain and intensifying the degenerative cascade response mediated by chemokines. Gaining a deeper comprehension of the functions of chemokines and immune cells in these processes involving catabolism, angiogenesis, and injury detection could offer novel therapeutic avenues for managing symptomatic disc disease.

Spt5 interacts genetically with Myc and is limiting for brain tumor growth in Drosophila.

The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured cells. Here, we use Drosophila to address the relevance of this interaction in a living organism. Spt5 displays moderate synergy with Myc in fast proliferating young imaginal disc cells. During later development, Spt5-knockdown has no detectable consequences on its own, but strongly enhances eye defects caused by Myc overexpression. Similarly, Spt5-knockdown in larval type 2 neuroblasts has only mild effects on brain development and survival of control flies, but dramatically shrinks the volumes of experimentally induced neuroblast tumors and significantly extends the lifespan of tumor-bearing animals. This beneficial effect is still observed when Spt5 is knocked down systemically and after tumor initiation, highlighting SPT5 as a potential drug target in human oncology.

Machine learning algorithm predicts fibrosis-related blood diagnosis markers of intervertebral disc degeneration

BackgroundIntervertebral disc cell fibrosis has been established as a contributing factor to intervertebral disc degeneration (IDD). This study aimed to identify fibrosis-related diagnostic genes for patients with IDD.MethodsRNA-sequencing data was downloaded from Gene Expression Omnibus (GEO) database. The diagnostic genes was identified using Random forest based on the differentially expressed fibrosis-related genes (DE-FIGs) between IDD and control samples. The immune infiltration states in IDD and the regulatory network as well as potential drugs targeted diagnostic genes were investigated. Quantitative Real-Time PCR was conducted for gene expression valifation.ResultsCEP120 and SPDL1 merged as diagnostic genes. Substantial variations were observed in the proportions of natural killer cells, neutrophils, and myeloid-derived suppressor cells between IDD and control samples. Further experiments indicated that AC144548.1 could regulate the expressions of SPDL1 and CEP120 by combininghsa-miR-5195-3p and hsa-miR-455-3p, respectively. Additionally, transcription factors FOXM1, PPARG, and ATF3 were identified as regulators of SPDL1 and CEP120 transcription. Notably, 56 drugs were predicted to target these genes. The down-regulation of SPDL1 and CEP120 was also validated.ConclusionThis study identified two diagnostic genes associated with fibrosis in patients with IDD. Additionally, we elucidated their potential regulatory networks and identified target drugs, which offer a theoretical basis and reference for further study into fibrosis-related genes involved in IDD.

Dilp8 and its candidate receptor, Drl, are involved in the transdetermination of the Drosophila imaginal disc.

Drosophila imaginal disc cells can change their identity under stress conditions through transdetermination (TD). Research on TD can help elucidate the in vivo process of cell fate conversion. We previously showed that the overexpression of winged eye (wge) induces eye-to-wing TD in the eye disc and that an insulin-like peptide, Dilp8, is then highly expressed in the disc. Although Dilp8 is known to mediate systemic developmental delay via the Lgr3 receptor, its role in TD remains unknown. This study showed that Dilp8 is expressed in specific cells that do not express eye or wing fate markers during Wge-mediated TD and that the loss of Dilp8 impairs the process of eye-to-wing transition. Thus, Dilp8 plays a pivotal role in the cell fate conversion under wge overexpression. Furthermore, we found that instead of Lgr3, another candidate receptor, Drl, is involved in Wge-mediated TD and acts locally in the eye disc cells. We propose a model in which Dilp8-Drl signaling organizes cell fate conversion in the imaginal disc during TD.

Impact of autophagy inhibition on intervertebral disc cells and extracellular matrix.

Intervertebral disc degeneration (IDD) is a leading contributor to low back pain (LBP). Autophagy, strongly activated by hypoxia and nutrient starvation, is a vital intracellular quality control process that removes damaged proteins and organelles to recycle them for cellular biosynthesis and energy production. While well-established as a major driver of many age-related diseases, autophagy dysregulation or deficiency has yet been confirmed to cause IDD. In vitro, rat nucleus pulposus (NP) cells treated with bafilomycin A1 to inhibit autophagy were assessed for glycosaminoglycan (GAG) content, proteoglycan synthesis, and cell viability. In vivo, a transgenic strain (Col2a1-Cre; Atg7 fl/fl) mice were successfully generated to inhibit autophagy primarily in NP tissues. Col2a1-Cre; Atg7 fl/fl mouse intervertebral discs (IVDs) were evaluated for biomarkers for apoptosis and cellular senescence, aggrecan content, and histological changes up to 12 months of age. Here, we demonstrated inhibition of autophagy by bafilomycin produced IDD features in the rat NP cells, including increased apoptosis and cellular senescence (p21 CIP1) and decreased expression of disc matrix genes Col2a1 and Acan. H&E histologic staining showed significant but modest degenerative changes in NP tissue of Col2a1-Cre; Atg7 fl/fl mice compared to controls at 6 and 12 months of age. Intriguingly, 12-month-old Col2a1-Cre; Atg7 fl/fl mice did not display increased loss of NP proteoglycan. Moreover, markers of apoptosis (cleaved caspase-3, TUNEL), and cellular senescence (p53, p16 INK4a , IL-1β, TNF-α) were not affected in 12-month-old Col2a1-Cre; Atg7 fl/fl mice compared to controls. However, p21 CIP1and Mmp13 gene expression were upregulated in NP tissue of 12-month-old Col2a1-Cre; Atg7 fl/fl mice compared to controls, suggesting p21 CIP1-mediated cellular senescence resulted from NP-targeted Atg7 knockout might contribute to the observed histological changes. The absence of overt IDD features from disrupting Atg7-mediated macroautophagy in NP tissue implicates other compensatory mechanisms, highlighting additional research needed to elucidate the complex biology of autophagy in regulating age-dependent IDD.

Preclinical to clinical translation for intervertebral disc repair: Effects of species-specific scale, metabolism, and matrix synthesis rates on cell-based regeneration.

A significant hurdle for potential cell-based therapies is the subsequent survival and regenerative capacity of implanted cells. While many exciting developments have demonstrated promise preclinically, cell-based therapies for intervertebral disc (IVD) degeneration fail to translate equivalent clinical efficacy. This work aims to ascertain the clinical relevance of both a small and large animal model by experimentally investigating and comparing these animal models to human from the perspective of anatomical scale and their cellular metabolic and regenerative potential. First, this work experimentally investigated species-specific geometrical scale, native cell density, nutrient metabolism, and matrix synthesis rates for rat, goat, and human disc cells in a 3D microspheroid configuration. Second, these parameters were employed in silico to elucidate species-specific nutrient microenvironments and predict differences in temporal regeneration between animal models. This work presents in silico models which correlate favorably to preclinical literature in terms of the capabilities of animal regeneration and predict that compromised nutrition is not a significant challenge in small animal discs. On the contrary, it highlights a very fine clinical balance between an adequate cell dose for sufficient repair, through de novo matrix deposition, without exacerbating the human microenvironmental niche. Overall, this work aims to provide a path towards understanding the effect of cell injection number on the nutrient microenvironment and the "time to regeneration" between preclinical animal models and the large human IVD. While these findings help to explain failed translation of promising preclinical data and the limited results emerging from clinical trials at present, they also enable the research field and clinicians to manage expectations on cell-based regeneration. Ultimately, this work provides a platform to inform the design of clinical trials, and as computing power and software capabilities increase in the future, it is conceivable that generation of patient-specific models could be used for patient assessment, as well as pre- and intraoperative planning.

A Review: Methodologies to Promote the Differentiation of Mesenchymal Stem Cells for the Regeneration of Intervertebral Disc Cells Following Intervertebral Disc Degeneration.

Intervertebral disc (IVD) degeneration (IDD), a highly prevalent pathological condition worldwide, is widely associated with back pain. Treatments available compensate for the impaired function of the degenerated IVD but typically have incomplete resolutions because of their adverse complications. Therefore, fundamental regenerative treatments need exploration. Mesenchymal stem cell (MSC) therapy has been recognized as a mainstream research objective by the World Health Organization and was consequently studied by various research groups. Implanted MSCs exert anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects and promote extracellular component production, as well as differentiation into IVD cells themselves. Hence, the ultimate goal of MSC therapy is to recover IVD cells and consequently regenerate the extracellular matrix of degenerated IVDs. Notably, in addition to MSC implantation, healthy nucleus pulposus (NP) cells (NPCs) have been implanted to regenerate NP, which is currently undergoing clinical trials. NPC-derived exosomes have been investigated for their ability to differentiate MSCs from NPC-like phenotypes. A stable and economical source of IVD cells may include allogeneic MSCs from the cell bank for differentiation into IVD cells. Therefore, multiple alternative therapeutic options should be considered if a refined protocol for the differentiation of MSCs into IVD cells is established. In this study, we comprehensively reviewed the molecules, scaffolds, and environmental factors that facilitate the differentiation of MSCs into IVD cells for regenerative therapies for IDD.

Intervertebral Disc-on-a-ChipMF: A New Model for Mouse Disc Culture via Integrating Mechanical Loading and Dynamic Media Flow.

This study aims to develop an ex vivo organ-on-a-chip model, intervertebral Disc-on-a-ChipMF, to investigate integrated effects of mechanical loading and nutrition on disc health. The system consists of a detachable multilayer microfluidic chip, a Computer-Arduino-based control system, and a mechanical loading unit, which were optimized for accurate axial force measurement and the maintenance of a 21-day ex vivo disc culture. To ensure accuracy of axial force, we optimized the axial mechanical loading regimen, used the Computer-Arduino-based system and low-profile force sensors (LPFS) to control the mechanical loading unit, and modeled the force distribution by using computational simulation. A 21-day ex vivo disc culture was demonstrated using the Disc-on-a-ChipMF system, with optimized mechanical loading (0.02 MPa at 1Hz, 1.5 hr/day) and flow rate (1 μL/min). The structural integrity, collagen breakdown, catabolic enzyme activities, and disc cell and collagen alignment revealed that the on-chip cultured discs exhibited a preferred disc health similar to that of native discs for up to 21 days, while discs in a static culture showed detrimental degenerative changes. The mouse Disc-on-a-ChipMF system mimics in vivo disc microenvironment and provides a valuable platform for studying the effects of various factors on disc health and degeneration and testing new therapies.

Fibronectin sensitizes activation of contractility, YAP, and NF-κB in nucleus pulposus cells.

Intervertebral disc degeneration involves the breakdown of the discs of the spine due to genetics, aging, or faulty mechanical loading. As part of the progression of the disease, nucleus pulposus cells lose their phenotypic characteristics, inducing inflammation and extracellular matrix (ECM) alterations that result in a loss of disc mechanical homeostasis. Fibronectin is one ECM molecule that has been shown to be upregulated in disc degeneration and plays an important role in the progression of a wide variety of fibrotic diseases. Fragments of fibronectin have also long been associated with both osteoarthritis and disc degeneration. The goal of this work isto test the effects of fibronectin on disc cell phenotype, mechanosensing, and inflammatory signaling. We identify that fibronectin increases the activation of cellular contractility, the mechanosensitive transcription factor Yes-associated protein, and the inflammatory transcription factor nuclear factor-κB. This results in decreased production and expression of proteoglycans, which are required to maintain healthy disc function. Thus, fibronectin is a potential regulator of phenotypic changes in disc degeneration, and a potential target for treating disc degeneration at the cellular level. Understanding the role of fibronectin, and its potential as a therapeutic target, could provide new approaches for preventing or reversing disc degeneration.

Nanog, Stat-3, and Sox-5 involvement in human fetal temporomandibular joint late development

Background and aimThe temporomandibular joint (TMJ) is a synovial joint that allows the complex movements essential for life. It connects the jawbone to the skull, working as a sliding hinge. Moreover, pluripotent stem cells are a source of precursors and tissue-specific cells in developing organisms, however, their biodistribution in developing fetal tissues is weakly studied. The aim of our study was analyse immunohistochemical expression of Nanog, Oct-4, Sox-2 and Stat-3 and Sox-5, in TMJ tissue samples from human fetuses aged between the 12th and 20th weeks of intrauterine life. Materials and methodsWe fixed and processed TMJ tissue samples from human fetuses, histological sections and immunohistochemical procedures were carried out. ResultsTMJ histological studies examination did not reveal any difference in the tissue organization between the samples in the studied periods. Immunohistochemical analysis demonstrated that Oct-4 and Sox-2 lack their expression in TMJ. In contrast, Nanog was expressed in nucleous of proliferative layer of mandibular condyle, Stat-3 was expressed in nuclear cells of articular disc, Stat-3 and Sox-5 showed positive nuclear and cytoplasmic immunostaining in codrocyte layers and in ossification areas. ConclusionsNanog acts in maintanence of pluripotency, Stat-3 in articular disc acts as a transcriptional factor. Stat-3 and Sox-2 act in chondrocyte and osteoblast diferentiation. Distribution of the cells, which express Nanog, Stat-3, and Sox-5 in TMJ tissue during fetal development, can help further understand its physiology, pathology, and repairing capacities.

Effects of Tocilizumab on Intervertebral Disc Degeneration, Cell Senescence and Inflammation via BMP-2, Hif-1α , IL-1β and SOX9

Effects of Tocilizumab on Intervertebral Disc Degeneration, Cell Senescence and Inflammation via BMP-2, Hif-1α , IL-1β and SOX9

Effective Modulation of Inflammation and Oxidative Stress for Enhanced Regeneration of Intervertebral Discs Using 3D Porous Hybrid Protein Nanoscaffold.

Degeneration of fibrocartilaginous tissues is often associated with complex pro-inflammatory factors. These include reactive oxygen species (ROS), cell-free nucleic acids (cf-NAs), and epigenetic changes in immune cells. To effectively control this complex inflammatory signaling, it developed an all-in-one nanoscaffold-based 3D porous hybrid protein (3D-PHP) self-therapeutic strategy for treating intervertebral disc (IVD) degeneration. The 3D-PHP nanoscaffold is synthesized by introducing a novel nanomaterial-templated protein assembly (NTPA) strategy. 3D-PHP nanoscaffolds that avoid covalent modification of proteins demonstrate inflammatory stimuli-responsive drug release, disc-mimetic stiffness, and excellent biodegradability. Enzyme-like 2D nanosheets incorporated into nanoscaffolds further enabled robust scavenging of ROS and cf-NAs, reducing inflammation and enhancing the survival of disc cells under inflammatory stress in vitro. Implantation of 3D-PHP nanoscaffolds loaded with bromodomain extraterminal inhibitor (BETi) into a rat nucleotomy disc injury model effectively suppressed inflammation in vivo, thus promoting restoration of the extracellular matrix (ECM). The resulting regeneration of disc tissue facilitated long-term pain reduction. Therefore, self-therapeutic and epigenetic modulator-encapsulated hybrid protein nanoscaffold shows great promise as a novel approach to restore dysregulated inflammatory signaling and treat degenerative fibrocartilaginous diseases, including disc injuries, providing hope and relief to patients worldwide.

The role of ferroptosis in intervertebral disc degeneration.

Nucleus pulposus, annulus fibrosus, and cartilage endplate constitute an avascular intervertebral disc (IVD), which is crucial for spinal and intervertebral joint mobility. As one of the most widespread health issues worldwide, intervertebral disc degeneration (IVDD) is recognized as a key contributor to back and neck discomfort. A number of degenerative disorders have a strong correlation with ferroptosis, a recently identified novel regulated cell death (RCD) characterized by an iron-dependent mechanism and a buildup of lipid reactive oxygen species (ROS). There is growing interest in the part ferroptosis plays in IVDD pathophysiology. Inhibiting ferroptosis has been shown to control IVDD development. Several studies have demonstrated that in TBHP-induced oxidative stress models, changes in ferroptosis marker protein levels and increased lipid peroxidation lead to the degeneration of intervertebral disc cells, which subsequently aggravates IVDD. Similarly, IVDD is significantly relieved with the use of ferroptosis inhibitors. The purpose of this review was threefold: 1) to discuss the occurrence of ferroptosis in IVDD; 2) to understand the mechanism of ferroptosis and its role in IVDD pathophysiology; and 3) to investigate the feasibility and prospect of ferroptosis in IVDD treatment.

A bioinspired and high-strengthed hydrogel for regeneration of perforated temporomandibular joint disc: Construction and pleiotropic immunomodulatory effects.

Due to the lack of an ideal material for TMJ (temporomandibular joint) disc perforation and local inflammation interfering with tissue regeneration, a functional TGI/HA-CS (tilapia type I gelatin/hyaluronic acid-chondroitin sulfate) double network hydrogel was constructed in this paper. It was not only multiply bionic in its composition, structure and mechanical strength, but also endowed with the ability to immunomodulate microenvironment and simultaneously induce in situ repair of defected TMJ discs. On the one hand, it inhibited inflammatory effects of inflammasome in macrophages, reduced the extracellular matrix (ECM)-degrading enzymes secreted by chondrocytes, reversed the local inflammatory state, promoted the proliferation of TMJ disc cells and induced fibrochondrogenic differentiation of synovium-derived mesenchymal stem cells (SMSCs). On the other hand, it gave an impetus to repairing a relatively-large (6mm-sized) defect in mini pigs' TMJ discs in a rapid and high-quality manner, which suggested a promising clinical application.

Effects of glucose concentration and oxygen partial pressure on the respiratory metabolism of sheep temporomandibular joint disc cells.

Temporomandibular joint (TMJ) disc degeneration is a common disease characterized by a decrease in metabolic function. The present study aimed to investigate the pathogenesis of TMJ disc degeneration by analyzing the effects of oxygen and glucose concentrations on metabolism in a simulated TMJ disc cell growth environment. Cell samples were divided into 10 groups and cultured in different nutritional environments, including 21 and 2% O2 partial pressures and various glucose concentrations (0, 0.5, 3, 5.5 and 22.5 mmol/l). Cell proliferation, extracellular matrix content, mitochondrial function, and cell metabolism were subsequently analyzed. The results demonstrated that hypoxia and a low glucose concentration inhibited cell growth, and low glucose concentration inhibited extracellular matrix synthesis and adenosine 5'-monophosphate-activated protein kinase expression. Hypoxic conditions also induced a compensatory increase in the number of mitochondria, whereas mitochondrial deformation and swelling were observed in the absence of glucose. According to this study, the primary metabolic pathway of TMJ disc cells is glycolysis. It was concluded that hypoxic conditions and normal glucose concentrations are needed for the growth of TMJ disc cells. Glucose is necessary to ensure cell survival, extracellular matrix synthesis and mitochondrial function. Glucose deficiency may be related to disc degeneration, aging and disease mechanisms.