Intervertebral Disc Mechanics

Intervertebral disc degeneration (IVDD) is a common chronic orthopaedic disease in orthopaedics that imposes a heavy economic burden on people and society. Although it is well established that IVDD is associated with genetic susceptibility, ageing and obesity, its pathogenesis remains incompletely understood. Previously, IVDD was thought to occur because of excessive mechanical loading leading to destruction of nucleus pulposus cells (NPCs), but studies have shown that IVDD is a much more complex process associated with inflammation, metabolic factors and NPCs death and can involve all parts of the disc, characterized by causing NPCs death and extracellular matrix (ECM) degradation...

OBJECTIVES: Investigating the impact of cadmium (Cd) on annulus fibrosus (AF) cells and its potential mechanism was the purpose of the current study. MATERIALS AND METHODS: Cd was cultivated in different concentrations (0, 1, 5, 10, and 20 μM) on AF cells and the potential effects of the metal were assessed. Using the CCK-8 method, cell viability and proliferation were identified. Using transcriptome analysis, the annulus fibrosus cells were sequenced both with and without cadmium chloride...

Degenerative intervertebral disc disease (IVDD) is one of the main spinal surgery, conditions, which markedly increases the incidence of low back pain and deteriorates the patient's quality of life, and it imposes significant social and economic burdens. The molecular pathology of IVDD is highly complex and multilateral however still not ompletely understood. New findings indicate that IVDD is closely associated with inflammation, oxidative stress, cell injury and extracellular matrix metabolismdysregulation...

BACKGROUND: Dorsal root ganglia (DRGs) contain sensory neurons that innervate intervertebral discs (IVDs) and may play a critical role in mediating low-back pain (LBP), but the potential pathophysiological mechanism needs to be clarified. METHODS: A discogenic LBP model in rats was established by penetration of a lumbar IVD. The severity of LBP was evaluated through behavioral analysis, and the gene and protein expression levels of pro-algesic peptide substance P (SP) and calcitonin gene-related peptide (CGRP) in DRGs were quantified...

BACKGROUND: Two main problems examining the mechanism of cancer progression in the tissues using the computational models are lack of enough knowledge on the effective factors for such events in vivo environments and lack of specific parameters in the available computational models to simulate such complicated reactions. METHODS: In this study, it was tried to simulate the progression of cancerous lesions in the bone tissues by an independent parameter from the anatomical and physiological characteristics of the tissues, so to degrade the orthotropic mechanical properties of the bone tissues, a virtual temperature was determined to be used by a well-known framework for simulation of damages in the composite materials...

OBJECTIVE: Transient receptor potential vanilloid 4 (TRPV4) is a multi-modally activated cation channel that mediates mechanotransduction pathways by which musculoskeletal tissues respond to mechanical load and regulate tissue health. Using conditional Trpv4 knockout mice, we investigated the role of Trpv4 in regulating intervertebral disc (IVD) health and injury-induced IVD degeneration. METHODS: Col2Cre;Trpv4fl/f (Trpv4 KO) mice were used to knockout Trpv4 in all type 2 collagen-expressing cells...

OBJECTIVE: Knee osteoarthritis (OA) is a disease of the whole joint involving multiple tissue types. MRI-based semi-quantitative (SQ) scoring of knee OA is a method to perform multi-tissue joint assessment and has been shown to be a valid and reliable way to measure structural multi-tissue involvement and progression of the disease. While recent work has described how SQ scoring may be used for clinical trial enrichment and disease phenotyping in OA, less guidance is available for how these parameters may be used to assess study outcomes...

Intervertebral disc degeneration (IDD) is an age-related disease and is responsible for low back pain. Oxidative stress-induced cell death plays a fundamental role in IDD pathogenesis. Cuproptosis is a recently discovered form of programmed cell death dependent on copper availability. Whether cuproptosis is involved in IDD progression remains unknown. Herein, we established in vitro and in vivo models to investigate cuproptosis in IDD and the mechanisms by which oxidative stress interacts with copper sensitivity in nucleus pulposus cells (NPCs)...

Extracellular vesicles (EVs) derived from Mesenchymal Stromal Cells (MSCs) have shown promising therapeutic potential for multiple diseases, including intervertebral disc degeneration (IDD). Nevertheless, the limited production and unstable quality of EVs hindered the clinical application of EVs in IDD. Selenomethionine (Se-Met), the major form of organic selenium present in the cereal diet, showed various beneficial effects, including antioxidant, immunomodulatory and anti-apoptotic effects. In the current study, Se-Met was employed to treat MSCs to investigate whether Se-Met can facilitate the secretion of EVs by MSCs and optimize their therapeutic effects on IDD...

Painful musculoskeletal disorders such as intervertebral disc (IVD) degeneration associated with chronic low back pain (termed "Discogenic back pain", DBP), are a significant socio-economic burden worldwide and contribute to the growing opioid crisis. Yet there are very few if any successful interventions that can restore the tissue's structure and function while also addressing the symptomatic pain. Here we have developed a novel non-viral gene therapy, using engineered extracellular vesicles (eEVs) to deliver the developmental transcription factor FOXF1 to the degenerated IVD in an in vivo model...

OBJECTIVE: Facet joint violation (FJV) is associated with postoperative low-back pain and is a confirmed risk factor for adjacent-segment degeneration, a long-term complication of lumbar fusion surgery. The authors' knowledge of its mechanisms comes from in vitro biomechanical research only; there is a lack of radiographic evidence of the effects of violation on the superior adjacent-segment facet joint, intervertebral disc, and other local radiographic parameters. Furthermore, any differences between unilateral and bilateral violation remain relatively unclear...

Utilization of injectable hydrogels stands as a paradigm of minimally invasive intervention in the context of intervertebral disc degeneration treatment. Restoration of nucleus pulposus (NP) function exerts a profound influence in alleviating back pain. This study introduces an innovative class of injectable shear-thinning hydrogels, founded on quaternized chitosan (QCS), gelatin (GEL), and laponite (LAP) with the capacity for sustained release of the anti-inflammatory drug, celecoxib (CLX). First, synthesis of Magnesium-Aluminum-Layered double hydroxide (LDH) was achieved through a co-precipitation methodology, as a carrier for celecoxib and a source of Mg ions...

Proteoglycans through their sulfated glycosaminoglycans regulate cell-matrix signaling during tissue development, regeneration, and degeneration processes. Large extracellular proteoglycans such as aggrecan, versican, and perlecan are especially important for the structural integrity of the intervertebral disc and cartilage during development. In these tissues, proteoglycans are responsible for hydration, joint flexibility, and the absorption of mechanical loads. Loss or reduction of these molecules can lead to disc degeneration and skeletal dysplasia, evident from loss of disc height or defects in skeletal development respectively...

Intervertebral disc degeneration (IDD) is one of the primary causes of low back pain (LBP), which seriously affects patients' quality of life. In recent years, interleukin (IL)-17 has been shown to be highly expressed in the intervertebral disc (IVD) tissues and serum of patients with IDD, and IL-17A has been shown to promote IDD through multiple pathways. We first searched databases such as PubMed, Cochrane, Embase, and Web of Science using the search terms "IL-17 or interleukin 17″ and "intervertebral discs"...

Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine...

BACKGROUND: Intervertebral disc degeneration (IVDD) is the main cause of low back pain (LBP), but the specific regulatory factors, pathways and specific molecular mechanisms remain unclear. METHODS: We identified and quantitatively analyzed Pfirrmann Grade II (n=3) and Pfirrmann Grade IV (n=3) pulposus samples via MRI. The differential abundance of proteins in the samples was determined and quantitatively analyzed by relative and absolute quantitative analysis of the isotope marker levels combined with the liquid chromatography-tandem mass spectrometry (LC‒MSMS/MS)...

The highly organized collagen network of human lumbar annulus fibrosus (AF) is fundamental to preserve the mechanical integrity of the intervertebral discs. In the healthy AF, fibers are embedded in a hydrated matrix and arranged in a crosswise fashion, giving an anisotropic structure capable to undergo large strains. For finite element analysis (FEA) of spine, modelling a realistic intervertebral disc geometry has always been a challenge. This paper proposes a simple yet efficient workflow details for generating structured mesh of the ground substance of the AF and the method for generating collagen fibers with controllable angles that are embedded in AF...

INTRODUCTION AND IMPORTANCE: Degenerative disc disease (DDD) is a common cause of low back pain, often leading to significant discomfort for patients. Current treatment options such as spinal fusion and physical therapy focus on symptom management rather than addressing the underlying degeneration. Percutaneous laser disc decompression (PLDD) has shown efficacy in treating radicular pain associated with disc herniation. However, there is a growing interest in utilizing tissue engineering approaches to reverse the pathological process of DDD...

Intervertebral disc degeneration (IDD) is a well-established cause of disability, and extensive evidence has identified the important role played by regulatory noncoding RNAs, specifically circular RNAs (circRNAs) and microRNAs (miRNAs), in the progression of IDD. To elucidate the molecular mechanism underlying IDD, we established a circRNA/miRNA/mRNA network in IDD through standardized analyses of all expression matrices. Our studies confirmed the differential expression of the transcription factors early B-cell factor 1 (EBF1), circEYA3, and miR-196a-5p in the nucleus pulposus (NP) tissues of controls and IDD patients...

Cellular senescence is a significant contributor to intervertebral disc aging and degeneration. However, the application of senotherapies, such as senomorphics targeting senescence markers and the senescence-associated secretory phenotype (SASP), remains limited due to challenges in precise delivery. Given that the natural killer group 2D (NKG2D) ligands are increased on the surface of senescent nucleus pulposus (NP) cells, the NKG2D-overexpressing NP cell membranes (NNPm) are constructed, which is expected to achieve a dual targeting effect toward senescent NP cells based on homologous membrane fusion and the NKG2D-mediated immunosurveillance mechanism...