Circulating microRNAs May Be Predictive of Degenerative Cervical Myelopathy.

Study Design: Basic Science.

Objective: The objective of this study was to identify a unique serum profile of circulating miRNAs and inflammatory markers in patients with degenerative cervical myelopathy (DCM) compared with healthy controls (HC).

Summary Of Background Data: Currently, DCM is diagnosed with a combination of history, physical examination, and close correlation to advanced imaging.

The Inhibitory Effect of NSAIDs and Opioids on Spinal Fusion: An Animal Model.

Study Design: Translational research.

Objective: To evaluate the relative effects of NSAIDs, opioids, and a combination of the two on spinal fusion inhibition in a rodent model.

Summary Of Background Data: Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are common postoperative analgesic agents.

Inhibition of Neurogenic Inflammatory Pathways Associated with the Reduction in Discogenic Back Pain.

Study Design: Retrospective cohort study.

Purpose: This study aimed to determine whether the initiation of anti-calcitonin gene-related peptide (CGRP inhibitor) medication therapy for migraines was also associated with improvements in back/neck pain, mobility, and function in a patient population with comorbid degenerative spinal disease and migraine.

Overview Of Literature: CGRP upregulates pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, brain-derived neurotrophic factor, and nerve growth factor in spinal spondylotic disease, which results in disc degeneration and sensitization of nociceptive neurons.

Do Inflammatory Cytokines Affect Patient Outcomes After ACDF?

Study Design: Prospective cohort study.

Objective: The aim was to determine the relationship between serum inflammatory mediators, preoperative cervical spine disease severity, and clinical outcomes after anterior cervical discectomy and fusion (ACDF).

Summary Of Background Data: Given the role of the inflammatory cascade in spinal degenerative disease, it has been hypothesized that inflammatory markers may serve as a predictor of patient outcomes after surgery.

Functional Deficits in Mice Expressing Human Interleukin 8.

We showed previously that inflammatory mediators, including IL8, in intervertebral disc tissues from patients with discogenic back pain may play a key role in back pain. To investigate the molecular mechanism of IL8 signaling in back pain, we generated a mouse model that conditionally expresses human (h) IL8. We hypothesized that hIL8 levels affect mouse activity and function.

Correlation of Early Outcomes and Intradiscal Interleukin-6 Expression in Lumbar Fusion Patients.

Objective: To determine if there is correlation between intradiscal levels of interleukin-6 (IL-6) and early outcome measures in patients undergoing lumbar fusion for painful disc degeneration.

Methods: Intervertebral disc tissue was separated into annulus fibrosus/nucleus pulposus and cultured separately in vitro in serum-free medium (Opti-MEM). Conditioned media was collected after 48 hours.

Circulating miR-155-5p as a Novel Biomarker of Lumbar Degenerative Disc Disease.

Unlabelled: MINI: Circulating microRNAs provide an insight into current disease states. Comparing patients with degenerative disc disease to healthy controls, patients with disc disease were found to have significantly downregulated levels of miR-155-5p. This marker was found to be an accurate diagnostic predictor for the presence of degeneration (P = 0.

Does Riluzole Influence Bone Formation?: An In Vitro Study of Human Mesenchymal Stromal Cells and Osteoblast.

Study Design: A post-test design biological experiment.

Objective: The aim of this study was to evaluate the osteogenic effects of riluzole on human mesenchymal stromal cells and osteoblasts.

Summary Of Background Data: Riluzole may benefit patients with spinal cord injury (SCI) from a neurologic perspective, but little is known about riluzole's effect on bone formation, fracture healing, or osteogenesis.

MicroRNA-145 overexpression attenuates apoptosis and increases matrix synthesis in nucleus pulposus cells.

Aims: Lower back pain is often associated with intervertebral disc degeneration (IDD), which results from a decrease in nucleus pulposus (NP) cells and an imbalance between the degradation and synthesis of extracellular matrix (ECM) components. Multiple microRNAs play crucial roles in the modulation of NP cell apoptosis and matrix degradation. miR-145 is an important microRNA related to degenerative diseases such as osteoarthritis.

The local cytokine and growth factor response to recombinant human bone morphogenetic protein-2 (rhBMP-2) after spinal fusion.

Background Context: The systemic response regarding cytokine expression after the application of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat spinal fusion model has recently been defined, but the local response has not been defined. Defining the local cytokine and growth factor response at the fusion site will help explain the roles of these molecules in the fusion process, as well as that of rhBMP-2. Our hypothesis is that the application of rhBMP-2 to the fusion site will alter the local levels of cytokines and growth factors throughout the fusion process, in a manner that is different from the systemic response, given the tissue-specific effects of rhBMP-2.

The Effect of Substance P on an Intervertebral Disc Rat Organ Culture Model.

Study Design: Laboratory study.

Objective: Evaluate the effect of substance P (SP) on an intervertebral disc rat organ culture model.

Summary Of Background Data: Monolayer cell experiments have demonstrated that exposure intervertebral disc tissue cells to SP leads to upregulation in inflammatory cytokine expression; however, this has not been evaluated in a more complex organ culture model.

Forelimb contractures and abnormal tendon collagen fibrillogenesis in fibulin-4 null mice.

Fibulin-4 is an extracellular matrix glycoprotein essential for elastic fiber formation. Mice deficient in fibulin-4 die perinatally because of severe pulmonary and vascular defects associated with the lack of intact elastic fibers. Patients with fibulin-4 mutations demonstrate similar defects, and a significant number die shortly after birth or in early childhood from cardiopulmonary failure.

Intervertebral Disc Cells Produce Interleukins Found in Patients with Back Pain.

Objective: To examine the link between cytokines in intervertebral disc (IVD) tissues and axial back pain.

Design: In vitro study with human IVD cells cultured from cadaveric donors and annulus fibrosus (AF) tissues from patients.

Results: Cultured nucleus pulposus (NP) and AF cells were stimulated with interleukin (IL)-1β.

Substance P Receptor Antagonist Suppresses Inflammatory Cytokine Expression in Human Disc Cells.

Study Design: Laboratory study.

Objective: To evaluate whether blockade of the Substance P (SP) NK1R attenuates its proinflammatory effect on human intervertebral disc cells (IVD), and to evaluate the signaling pathways associated with SP.

Summary Of Background Data: SP and its receptors are expressed in human IVD cells, and cause upregulation of inflammatory mediators; however, the effects of blocking these receptors have not been studied in human IVD cells.

Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells.

Objectives of this study were to investigate whether AQP1 and AQP5 expression is altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate their expression in NP cells. AQP expression was measured in human tissues from different degenerative grades; regulation by hypoxia and HIF-1 was studied using promoter analysis and gain- and loss-of-function experiments. We show that both AQPs are expressed in the disc and that mRNA and protein levels decline with human disease severity.

Xylosyltransferase-1 expression is refractory to inhibition by the inflammatory cytokines tumor necrosis factor α and IL-1β in nucleus pulposus cells: novel regulation by AP-1, Sp1, and Sp3.

We investigated whether expression of xylosyltransferase-1 (XT-1), a key enzyme in glycosaminoglycan biosynthesis, is responsive to disk degeneration and to inhibition by the inflammatory cytokines tumor necrosis factor α and IL-1β in nucleus pulposus (NP) cells. Analysis of human NP tissues showed that XT-1 expression is unaffected by degeneration severity; XT-1 and Jun, Fos, and Sp1 mRNA were positively correlated. Cytokines failed to inhibit XT-1 promoter activity and expression.

Fibronectin splice variation in human knee cartilage, meniscus and synovial membrane: observations in osteoarthritic knee.

Fibronectin (FN) is a widely expressed molecule that can participate in development of osteoarthritis (OA) affecting cartilage, meniscus, and synovial membrane (SM). The alternatively spliced isoforms of FN in joint tissues other than cartilage have not been extensively studied previously. The present study compares FN splice variation in patients with varying degrees of osteoarthritic change.

Differential gene expression in anterior and posterior annulus fibrosus.

Study Design: Laboratory study.

Objective: To evaluate the differential gene expression of cytokines and growth factors in anterior versus posterior annulus fibrosus (AF) intervertebral disc (IVD) specimens.

Summary Of Background Data: Histological analysis has demonstrated regional differences in vascular and neural ingrowth in the IVD, and similar differences may exist for cytokine and growth factor expression in patients with degenerative disc disease (DDD).

Fibronectin fragments and the cleaving enzyme ADAM-8 in the degenerative human intervertebral disc.

Study Design: The presence of fibronectin fragments (FN-fs) and the cleaving enzyme, A disintegrin and metalloproteinase domain-containing protein (ADAM)-8 were examined in human intervertebral disc (IVD) tissue in vitro.

Objective: To investigate the presence and pathophysiological concentration of FN-fs and their cleaving enzyme, ADAM-8, in the human IVD tissue.

Summary Of Background Data: The 29-kDa FN-f has been shown to result in extracellular matrix loss in rabbit IVDs.

FIH-1-Mint3 axis does not control HIF-1 transcriptional activity in nucleus pulposus cells.

The objective of this study was to determine the role of FIH-1 in regulating HIF-1 activity in the nucleus pulposus (NP) cells and the control of this regulation by binding and sequestration of FIH-1 by Mint3. FIH-1 and Mint3 were both expressed in the NP and were shown to strongly co-localize within the cell nucleus. Although both mRNA and protein expression of FIH-1 decreased in hypoxia, only Mint3 protein levels were hypoxiasensitive.

CCN2 suppresses catabolic effects of interleukin-1β through α5β1 and αVβ3 integrins in nucleus pulposus cells: implications in intervertebral disc degeneration.

The objective of the study was to examine the regulation of CCN2 by inflammatory cytokines, IL-1β, and TNF-α and to determine whether CCN2 modulates IL-1β-dependent catabolic gene expression in nucleus pulposus (NP) cells. IL-1β and TNF-α suppress CCN2 mRNA and protein expression in an NF-κB-dependent but MAPK-independent manner. The conserved κB sites located at -93/-86 and -546/-537 bp in the CCN2 promoter mediated this suppression.

An organ culture system to model early degenerative changes of the intervertebral disc II: profiling global gene expression changes.

Introduction: Despite many advances in our understanding of the molecular basis of disc degeneration, there remains a paucity of preclinical models which can be used to study the biochemical and molecular events that drive disc degeneration, and the effects of potential therapeutic interventions. The goal of this study is to characterize global gene expression changes in a disc organ culture system that mimics early nontraumatic disc degeneration.

Methods: To mimic a degenerative insult, rat intervertebral discs were cultured in the presence of TNF-α, IL-1β and serum-limiting conditions.