Intervertebral Disc Mechanics

BACKGROUND: Intervertebral disc degeneration (IVDD) is one of the etiologic factors of degenerative spinal diseases, which can lead to a variety of pathological spinal conditions such as disc herniation, spinal stenosis, and scoliosis. IVDD is a leading cause of lower back pain, the prevalence of which increases with age. Recently, Sirtuins/SIRTs and their related activators have received attention for their activity in the treatment of IVDD. In this paper, a comprehensive systematic review of the literature on the role of SIRTs and their activators on IVDD in recent years is presented...

To date, several molecules have been found to facilitate iron influx, while the types of iron influx channels remain to be elucidated. Here, Piezo1 channel was identified as a key iron transporter in response to mechanical stress. Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells (NPCs). Importantly, Piezo1-induced iron influx was independent of the transferrin receptor (TFRC), a well-recognized iron gatekeeper. Furthermore, pharmacological inactivation of Piezo1 profoundly reduced iron accumulation, alleviated mitochondrial ROS, and suppressed ferroptotic alterations in stimulation of mechanical stress...

OBJECTIVE: To explore whether Bushen Huoxue Formula (BSHXF) improves the angiogenesis ability of transplanted endothelial progenitor cells (EPCs) in endplate and its potential mechanism in delaying intervertebral disc degeneration (IDD). METHODS: BSHXF was analyzed via Ultra-High Performance Liquid Chromatography (UPLC). Rabbit axial compression lumbar IDD models were constructed and the effects of BSHXF, EPCs, and their combination in IDD were determined by MRI, histological evaluation, TUNEL, and immunofluorescence assays...

Intervertebral disc degeneration (IDD) poses a significant health burden, necessitating a deeper understanding of its molecular underpinnings. Transcriptomic analysis reveals 485 differentially expressed genes (DEGs) associated with IDD, underscoring the importance of immune regulation. Weighted gene co-expression network analysis (WGCNA) identifies a yellow module strongly correlated with IDD, intersecting with 197 DEGs. Protein-protein interaction (PPI) analysis identifies ITGAX, MMP9 and FCGR2A as hub genes, predominantly expressed in macrophages...

The intervertebral disc is not isolated from other tissues. Recently, abundant research has linked intervertebral disc homeostasis and degeneration to various systemic diseases, including obesity, metabolic syndrome, and diabetes. Organokines are a group of diverse factors named for the tissue of origin, including adipokines, osteokines, myokines, cardiokines, gastrointestinal hormones, and hepatokines. Through endocrine, paracrine, and autocrine mechanisms, organokines modulate energy homeostasis, oxidative stress, and metabolic balance in various tissues to mediate cross-organ communication...

Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect...

Ferroptosis has recently been shown to play a significant role in the progression of intervertebral disk degeneration (IDD), although the underlying mechanism is still unknown. The objective of this work was to use stringent bioinformatic techniques to clarify the crucial roles played by genes associated with ferroptosis in the emergence of IDD. For additional study, the microarray data pertinent to the IDD were acquired from the Gene Expression Omnibus database. The ferroptosis-related and IDD-related genes (FIDDRGs) were identified using a variety of bioinformatic techniques, which were also used to carry out function enrichment analysis, protein-protein correlation analysis, build the correlation regulatory network, and examine the potential connections between ferroptosis and immune abnormalities and inflammatory responses in IDD...

Intervertebral disc degeneration (IVDD) stands as the primary cause of low back pain (LBP). A significant contributor to IVDD is nucleus pulposus cell (NPC) senescence. However, the precise mechanisms underlying NPC senescence remain unclear. Monoacylglycerol lipase (MAGL) serves as the primary enzyme responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), breaking down monoglycerides into glycerol and fatty acids. It plays a crucial role in various pathological processes, including pain, inflammation, and oxidative stress...

OBJECTIVE: Mobile artificial lumbar complex (MALC) which suitable for reconstruction after subtotal lumbar resection in goats was developed,and to test stability of the complex and postoperative lumbar segmental motor function. METHODS: Eighteen male boer goats aged from 1 to 2 years old (weighted from 35 to 45 kg) were selected and divided into control group,fusion group and non-fusion group,with 6 goats in each group. According to preoperative CT scans and MRI examinations of lumbar,the goat MALC was designed and performed by 3D printed for non-fusion group...

AIMS: Intervertebral disc degeneration (IDD) is closely related to low back pain (LBP), which is a prevalent age-related problem worldwide; however, the mechanism underlying IDD is unknown. Glutamine, a free amino acid prevalent in plasma, is recognized for its anti-inflammatory and antioxidant properties in various diseases, the current study aims to clarify the effect and mechanism of glutamine in IDD. RESULTS: A synergistic interplay was observed between pyroptosis and ferroptosis within degenerated human disc specimens...

UNLABELLED: As a permanent state of cell cycle arrest, cellular senescence has become an important factor in aging and age-related diseases. As a central regulator of physiology and pathology associated with cellular senescence, the senescence associated secretory phenotype can create an inflammatory and catabolic environment through autocrine and paracrine ways, ultimately affecting tissue microstructure. As an age-related disease, the correlation between intervertebral disc degeneration and cellular senescence has been confirmed by many studies...

Degradation of extracellular matrix (ECM), reactive oxygen species (ROS) production, and inflammation are critical players in the pathogenesis of intervertebral disc degeneration (IDD). Evodiamine exerts functions in inhibiting inflammation and maintaining mitochondrial antioxidant functions. However, the biological functions of evodiamine and its related mechanisms in IDD progression remain unknown. The IDD-like conditions in vivo were stimulated via needle puncture. Hematoxylin and eosin staining, Safranin O/Fast Green staining and Alcian staining were performed to determine the degenerative status...

As the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socioeconomic challenge to the aging population and is largely attributed to intervertebral disc degeneration (IVDD). Elastic nucleus pulposus (NP) tissue is essential for the maintenance of IVD structural and functional integrity. The accumulation of senescent NP cells with an inflammatory hypersecretory phenotype due to aging and other damaging factors is a distinctive hallmark of IVDD initiation and progression. In this study, we reveal a mechanism of IVDD progression in which aberrant genomic DNA damage promoted NP cell inflammatory senescence via activation of the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) axis but not of absent in melanoma 2 (AIM2) inflammasome assembly...

The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1β-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1)...

BACKGROUND: Intervertebral disc degeneration (IVDD) is an essential cause of low back pain (LBP), the incidence of which has risen in recent years and is progressively younger, but treatment options are limited, placing a serious economic burden on society. Sanbi decoction (SBD) is an important classical formula for the treatment of IVDD, which can significantly improve patients' symptoms and is a promising alternative therapy. PURPOSE: The aim of this study is to investigate the safety and efficacy of SBD in the treatment of IVDD and to explore the underlying mechanisms by using an integrated analytical approach of microbiomics and serum metabolomics, as well as by using molecular biology...

In vitro studies investigating the effect of high physiological compressive loads on the intervertebral disc mechanics as well as on its recovery are rare. Moreover, the osmolarity effect on the disc viscoelastic behavior following an overloading is far from being studied. This study aims to determine whether a compressive loading-unloading cycle exceeding physiological limits could be detrimental to the cervical disc, and to examine the chemo-mechanical dependence of this overloading effect. Cervical functional spine units were subjected to a compressive loading-unloading cycle at a high physiological level (displacement of 2...

BACKGROUND: Lumbar disc herniation (LDH) is a common spinal disease that can cause severe radicular pain. Massage, also known as Tuina in Chinese, has been indicated to exert an analgesic effect in patients with LDH. Nonetheless, the mechanism underlying this effect of massage on LDH remains unclarified. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups. A rat LDH model was established by autologous nucleus pulpous (NP) implantation, followed by treatment with or without massage...

Intervertebral disc degeneration (IVDD) is an aging disease that results in a low quality of life and heavy socioeconomic burden. The mitochondrial unfolded protein response (UPRmt ) take part in various aging-related diseases. Our research intents to explore the role and underlying mechanism of UPRmt in IVDD. Nucleus pulposus (NP) cells were exposed to IL-1β and nicotinamide riboside (NR) served as UPRmt inducer to treat NP cells. Detection of ATP, NAD + and NADH were used to determine the function of mitochondria...

NP cells of the intervertebral disc and articular chondrocytes reside in avascular and hypoxic tissue niches. As a consequence of these environmental constraints the cells are primarily glycolytic in nature and were long thought to have a minimal reliance on mitochondrial function. Recent studies have challenged this long-held view and highlighted the increasingly important role of mitochondria in the physiology of these tissues. However, the foundational understanding of mechanisms governing mitochondrial dynamics and function in these tissues is lacking...

INTRODUCTION: Spondylolisthesis is described as the displacement of one vertebra over another, leading to spinal instability and potential nerve compression. When this occurs in the cervicothoracic junction, it can result in unique clinical manifestations. High-grade spondylolisthesis caused by trauma in the cervicothoracic junction of the spine usually results in acute spinal cord injury and quadriparesis. However, a few uncommon cases of the same injury reported minimal or no neurological deficits...