Abstract In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of cytokine IL-1, and locally produced can induce cellular matrix changes IVD degeneration. Immunohistochemistry was used to localize five members IL-1 family (IL-1α, IL-1β, IL-1Ra (IL-1 receptor antagonist), IL-1RI receptor, type I), ICE (IL-1β-converting enzyme)) non-degenerate degenerate IVDs. addition, cells derived from IVDs were challenged with agonists...

Abstract Low back pain is a common and debilitating disorder. Current evidence implicates intervertebral disc (IVD) degeneration herniation as major causes, although the pathogenesis poorly understood. While several cytokines have been implicated in process of IVD herniation, investigations predominately focused on Interleukin 1 (IL-1) tumor necrosis factor alpha (TNFα). However, to date no studies investigated expression these simultaneously or determined which may be predominant cytokine...

Abstract The histological and biochemical changes that occur in the extracellular matrix of intervertebral disc (IVD) during ageing degeneration have been investigated extensively. However, mechanisms behind these are not fully understood. A number studies suggested involvement metalloproteinases (MMPs) ADAMTS IVD degeneration, but few localized site production enzymes to cells degenerate disc. This study uses immunohistochemical techniques localize quantify degrading (MMPs 1, 3, 13, 4)...

Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this due cellular senescence, which causes fundamental changes in the ability cells maintain (IVD) matrix, thus leading IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean...

ABSTRACT Low back pain is a major physical and socioeconomic problem. Degeneration of the intervertebral disc especially that nucleus pulposus (NP) has been linked to low pain. In spite much research focusing on NP, consensus among community lacking in defining NP cell phenotype. A agreement will allow easier distinguishing cells from annulus fibrosus (AF) endplate chondrocytes, better gauge therapeutic success, guidance tissue‐engineering‐based regenerative strategies attempt replace lost...

Abstract The ability to control nanostructure shape and dimensions presents opportunities design materials in which their macroscopic properties are dependent upon the nature of nanoparticle. Although particle morphology has been recognized as a crucial parameter, exploitation potential shape-dependent has, date, limited. Herein, we demonstrate that nanoparticle is critical consideration determination nanocomposite hydrogel properties. Using translationally relevant calcium-alginate...

The use of tough hydrogels as biomaterials is limited a consequence time-consuming fabrication techniques, toxic starting materials, and large strain hysteresis under deformation. Herein, we report the simultaneous application nucleophilic thiol-yne inverse electron-demand Diels–Alder additions to independently create two interpenetrating networks in simple one-step procedure. resultant display compressive stresses 14–15 MPa at 98% compression without fracture or upon repeated load. hydrogel...

Low back pain is one of the largest health problems in Western world today, and intervertebral disc degeneration has been identified as a main cause. Currently, treatments are symptomatic, but cell-based tissue engineering methods realistic alternatives for regeneration. However, major problem these strategies generation suitable population cells. Adult bone marrow-derived mesenchymal stem cells (MSCs) undifferentiated, multipotent that have ability to differentiate into number cell types,...

Abstract Objective Intervertebral disc degeneration is linked to loss of extracellular matrix (ECM), particularly the early aggrecan. A group metalloproteinases called aggrecanases are important mediators aggrecan turnover. The present study was undertaken investigate expression recognized and their inhibitor, tissue inhibitor 3 (TIMP‐3), in human intervertebral tissue. Methods Twenty‐four nondegenerated 30 degenerated samples were analyzed for absolute messenger RNA (mRNA) copy number...

Abstract Introduction Nucleus pulposus (NP) cells have a phenotype similar to articular cartilage (AC) cells. However, the matrix of NP is clearly different that AC suggesting specific cell phenotypes exist. The aim this study was identify novel genes could be used distinguish bovine from and annulus fibrosus (AF) cells, further determine their expression in normal degenerate human intervertebral disc (IVD) Methods Microarrays were conducted on AC, AF using Affymetrix Genechip ® Bovine...

Objective. To establish if IL-1 or TNF regulates matrix degradation in the non-degenerate degenerate intervertebral disc (IVD). Methods. In situ zymography (ISZ) has been used to investigate role of and characterizing symptomatic IVD degeneration. ISZ employed three substrates (gelatin, collagen II, casein) four different challenges, IL-1β, receptor antagonist (IL-1Ra), TNF-α anti-TNF. Results. We have shown for first time that whilst IL-1β will stimulate inhibit intact human tissue, neither...

Abstract Objective Development of stem cell therapies for regenerating the nucleus pulposus (NP) are hindered by lack specific markers which to distinguish NP cells from articular chondrocytes (ACs). The purpose this study was define phenotype profile human using gene expression profiling and assess whether identified could mesenchymal (MSC) differentiation a correct phenotype. Methods Affymetrix MicroArray analyses were conducted on ACs, differential levels several positive negative (AC)...

The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic (BDNF) have been identified in the human intervertebral disc (IVD) implicated mechanisms associated with ingrowth nociception degeneration of IVD. aim current study was to investigate an association between neurotrophin expression IVD severity degeneration, including effect disc-related proinflammatory cytokines on neuropeptide cells derived from IVD.Immunohistochemical analysis performed examine NGF, BDNF their...

<h3>OBJECTIVES</h3> Matrix metalloproteinases (MMPs) are thought to be major mediators of cartilage destruction. Osteoarthritis (OA) is characterised by degradation. This study explores gene expression three MMPs in articular chondrocytes during the histological development lesion OA. <h3>METHODS</h3> Biopsy specimens human normal and OA cartilage, classified into four grades on basis histology, were probed for 1, 3, 9 using ³⁵S-labelled cDNA probes. The signal was measured at...

Abstract Introduction The aim of this study was to compare the effects tumour necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β) on protease catabolic cytokine receptor gene expression in normal degenerate human nucleus pulposus cells alginate culture. Methods Cells isolated from regions intervertebral discs were cultured pellets stimulated by addition 10 ng/mL TNF-α or IL-1β for 48 hours prior RNA extraction. Quantitative real-time polymerase chain reaction used assess effect IL-β...

Abstract Data implicate IL-1 in the altered matrix biology that characterizes human intervertebral disc (IVD) degeneration. In current study we investigated enzymic mechanism by which induces degradation degeneration of IVD, and whether inhibitor receptor antagonist (IL-1Ra) will inhibit degradation. A combination situ zymography (ISZ) immunohistochemistry was used to examine effects IL-1Ra on metal-dependent protease (MDP) expression explants non-degenerate degenerate IVDs. ISZ employed...

While mesenchymal stem cell (MSC)-based therapies for repair of the degenerate intervertebral disc (IVD) have been proposed, interaction MSCs with cells IVD has not fully investigated. Therefore, it is unclear whether implanted would differentiate into nucleus pulposus (NP) and/or stimulate endogenous NP cells. Here, we investigate differences in between human and from both nondegenerate discs during vitro co-culture direct cell-cell contact.Human bone marrow-derived (labeled CFDA) were...

Objectives The circadian clocks are internal timing mechanisms that drive ∼24-hour rhythms in a tissue-specific manner. Many aspects of the physiology intervertebral disc (IVD) show clear diurnal rhythms. However, it is unknown whether IVD tissue contains functional and if so, how their dysregulation implicated degeneration. Methods Clock gene dynamics ex vivo explants (from PER2:: luciferase (LUC) reporter mice) human cells (transduced with lentivirus containing Per2 ::luc reporters) were...