Mechanism of Intervertebral Disc Degeneration via the β-Catenin/CCL2 Pathway in Sox9 Conditional Knockout Mice.

Introduction: Degenerative changes in the intervertebral disc (IVD) are known to be a main cause of low back pain (LBP), oftentimes necessitating interventions that may or may not be successful due to a lack of understanding in the degenerative phenotype and its mechanisms. Understanding the molecular mechanisms of disc degeneration can help design new therapies to induce disc regeneration and reduce back pain. This work aimed to understand the effects of conditional deletion of Sox9 in aggrecan-expressing cells on intervertebral disc degeneration and its underlying mechanisms in mice.

Characterization of bone & cartilage endplate junction in the human lumbar spine: novel ultrastructural insights & association with elemental composition, vascularity and degeneration.

Objective: Intervertebral disc (IVD)-related pathology is associated with integrity of cartilaginous endplate (CEP), bony endplate (BEP) and their junction. However, ultrastructural details of the CEP, BEP and IVD and their interplay with disc degenerative features such as fissures and calcification are understudied. The current study aimed to ultra structurally explore CEP-BEP junction to IVD features.

Discovery of circulating blood biomarkers in patients with and without Modic changes of the lumbar spine: a preliminary analysis.

Purpose: The following study aimed to determine the existence of blood biomarkers in symptomatic patients with or without lumbar Modic changes (MC).

Methods: A cross-sectional sub-analyses of a prospective cohort was performed. Fasting blood samples were collected from patients with and without lumbar MC who had undergone spinal fusion or microdiscectomy.

Phenylpropanoid-enriched broccoli seedling extract can reduce inflammatory markers and pain behavior.

Background: Pain is a worldwide problem requiring an effective, affordable, non-addictive therapy. Using the edible plant broccoli, a growth protocol was developed to induce a concentrated combinatorial of potential anti-inflammatories in seedlings.

Methods: A growth method was utilized to produce a phenylpropanoid-rich broccoli sprout extract, referred to as Original Extract (OE).

The impact of novel inflammation-preserving treatment towards lumbar disc herniation resorption in symptomatic patients: a prospective, multi-imaging and clinical outcomes study.

Purpose: We performed a prospective one-year multi-imaging study to assess the clinical outcomes and rate of disc resorption in acute lumbar disc herniation (LDH) patients undergoing inflammation-preserving treatment (i.e. no NSAIDS, steroids).

The Human Microbiome and Its Role in Musculoskeletal Disorders.

Musculoskeletal diseases (MSDs) are characterized as injuries and illnesses that affect the musculoskeletal system. MSDs affect every population worldwide and are associated with substantial global burden. Variations in the makeup of the gut microbiota may be related to chronic MSDs.

Biodegradable Microspheres and Hydrogel Drug Delivery System of Tumor Necrosis Factor (TNF) Inhibitor and Growth Differentiation Factor 5 (GDF5) Reduces Disk Inflammation in the Rabbit Model.

Study Design: Preclinical study.

Objective: Develop and test a drug delivery system (DDS) composed of anti-inflammatories and growth factors in the rabbit disk injury model.

Summary Of Background Data: Biological therapies that inhibit inflammation or enhance cell proliferation can alter intervertebral disk (IVD) homeostasis to favor regeneration.

Harmonization and standardization of nucleus pulposus cell extraction and culture methods.

Background: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources.

Small molecule antagonist of C-C chemokine receptor 1 (CCR1) reduces disc inflammation in the rabbit model.

Background Context: Targeting chemokines or chemokine receptors is a promising treatment strategy for diseases with chronic inflammation such as rheumatoid arthritis and discogenic pain. Identifying specific molecules and determining their effectiveness in animal models are the first steps in developing these treatments. Macrophage markers have been detected in the intervertebral disc tissues of patients with disc degenerative disease and discogenic pain and in different animal models.

Anti-inflammatory effects of interleukin-4 on intervertebral disc cells.

Background Context: Inflammation has been associated with a number of pathological conditions including intervertebral disc (IVD) degeneration, increased risks of low back pain and other spinal diseases. Downregulating disc inflammation may be a strategy to reduce degeneration and more importantly back pain. Interleukin (IL)-4 was first discovered as a T-cell secreted factor that enhanced the proliferation of anti-IgM stimulated B cells and is now known as a cytokine that can stimulate cell proliferation and differentiation, tissue regeneration and neurological functions.

Therapeutic effects of cell therapy with neonatal human dermal fibroblasts and rabbit dermal fibroblasts on disc degeneration and inflammation.

Background Context: Increasing evidence suggests transplanting viable cells into the degenerating intervertebral disc (IVD) may be effective in treating disc degeneration and back pain. Clinical studies utilizing autologous or allogeneic mesenchymal stem cells to treat patients with back pain have reported some encouraging results. Animal studies have shown that cells injected into the disc can survive for months and have regenerative effects.

Annulus fibrosus cells express and utilize C-C chemokine receptor 5 (CCR5) for migration.

Background Context: Disc degeneration is associated with the progressive loss of the proteoglycan content of the intervertebral disc, decreased matrix synthesis, higher concentrations of proteolytic enzymes, and increased levels of proinflammatory cytokines. In previous studies, we have shown that C-C chemokine ligand (CCL)2, CCL3, and CCL5 are highly expressed by cultured nucleus pulposus (NP) and annulus fibrosus (AF) cells that have been treated by interleukin-1. The major function of these chemokines is to recruit immune cells into the disc.

Cell Therapy with Human Dermal Fibroblasts Enhances Intervertebral Disk Repair and Decreases Inflammation in the Rabbit Model.

 Pilot study using the rabbit model.  Low back pain is often associated with disk degeneration. Cell therapy for degenerating disks may promote tissue regeneration and repair.

Biglycan Inhibits Capsaicin-Induced Substance P Release by Cultured Dorsal Root Ganglion Neurons.

Objective: The purpose of this study was to examine the inhibitory effects of biglycan on substance P release from cultured sensory neurons in response to capsaicin.

Study Design: In vitro study of cultured primary sensory neurons from the rabbit dorsal root ganglion (DRG). We interrogated the culture system function with capsaicin.

Rho-Associated Kinase Inhibitor Immortalizes Rat Nucleus Pulposus and Annulus Fibrosus Cells: Establishment of Intervertebral Disc Cell Lines With Novel Approaches.

Study Design: Establishment of immortalized cell lines derived from rat intervertebral disc cells by Rho-associated kinase (ROCK) inhibitor, Y-27632.

Objective: To determine whether rat nucleus pulposus (NP) and annulus fibrosus (AF) cells could be immortalized, retain their phenotype, and used as cell lines for in vitro cell biology.

Summary Of Background Data: Intervertebral disc degeneration is a major factor for most low-back pain.

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.

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.

MicroRNA-146a reduces IL-1 dependent inflammatory responses in the intervertebral disc.

Because miR-146a expression in articular chondrocytes is associated with osteoarthritis (OA), we assessed whether miR-146a is linked to cartilage degeneration in the spine. Monolayer cultures of nucleus pulposus (NP) cells from the intervertebral discs (IVD) of bovine tails were transfected with a miR-146a mimic. To provoke inflammatory responses and catabolic extracellular matrix (ECM) degradation, cells were co-treated with interleukin-1 (IL-1).

Allogeneic Articular Chondrocyte Transplantation Downregulates Interleukin 8 Gene Expression in the Degenerating Rabbit Intervertebral Disk In Vivo.

Objective: The aim of this study was to investigate whether repopulating the degenerating intervertebral disk (IVD) with articular chondrocytes will decrease inflammation in the degenerating rabbit IVD.

Design: This was a biologic study in a rabbit IVD-injury model in vivo. Dual cell tracking methods (infrared dye labeling and adenovirus transduction) were used to demonstrate the viability of allogeneic articular chondrocytes injected into degenerating rabbit IVDs.

Cytotoxicity of local anesthetics and nonionic contrast agents on bovine intervertebral disc cells cultured in a three-dimensional culture system.

Background Context: Carragee et al. reported an accelerated progression of lumbar intervertebral disc (IVD) degeneration after discography in a human trial. Local anesthetics and contrast agents have exhibited toxicity to cardiac, renal, and neuronal cells.

Human umbilical cord blood-derived mesenchymal stem cells in the cultured rabbit intervertebral disc: a novel cell source for disc repair.

Objective: Back pain associated with symptomatic disc degeneration is a common clinical condition. Intervertebral disc (IVD) cell apoptosis and senescence increase with aging and degeneration. Repopulating the IVD with cells that could produce and maintain extracellular matrix would be an alternative therapy to surgery.

Retroperitoneal approach to the intervertebral disc for the annular puncture model of intervertebral disc degeneration in the rabbit.

Background Context: The rabbit annular puncture model of degeneration is among the most widely used models of intervertebral disc (IVD) degeneration. There are no published reports of the specific surgical technique used to produce this model.

Purpose: To describe the model in detail in an effort to reduce center-to-center variability and hopefully improve the reproducibility of future experimental results.