Local FK506 delivery induces osteogenesis in rat bone defect and rabbit spine fusion models.

Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and increase surgical costs, adding to patients' already high economic and mental burden.

Local FK506 delivery induces osteogenesis in rat bone defect and rabbit spine fusion models.

Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and significantly increase surgical costs, adding to patients' already high economic and mental burden.

Comparative Complications Associated With BMP Use In Patients Undergoing ACDF for Degenerative Spinal Conditions: Systematic Review and Meta-Analysis.

Study Design: Systematic Review and Meta-Analysis.

Objectives: To compare complication incidence in patients with or without the use of recombinant human Bone Morphogenic Protein-2 (BMP2) undergoing anterior cervical discectomy and fusion (ACDF) for degenerative conditions.

Methods: A systematic search of eight online databases was conducted using PRISMA guidelines.

Sclerostin small-molecule inhibitors promote osteogenesis by activating canonical Wnt and BMP pathways.

Background: The clinical healing environment after a posterior spinal arthrodesis surgery is one of the most clinically challenging bone-healing environments across all orthopedic interventions due to the absence of a contained space and the need to form de novo bone. Our group has previously reported that sclerostin in expressed locally at high levels throughout a developing spinal fusion. However, the role of sclerostin in controlling bone fusion remains to be established.

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.

The temporal and spatial expression of sclerostin and Wnt signaling factors during the maturation of posterolateral lumbar spine fusions.

The bone healing environment in the posterolateral spine following arthrodesis surgery is one of the most challenging in all of orthopedics and our understanding of the molecular signaling pathways mediating osteogenesis during spinal fusion is limited. In this study, the spatial and temporal expression pattern of Wnt signaling factors and inhibitors during spinal fusion was assessed for the first time. Bilateral posterolateral spine arthrodesis with autologous iliac crest bone graft was performed on 21 New Zealand White rabbits.

AAV6 as an effective gene delivery vector for prolonged transgene expression in intervertebral disc cells .

Intervertebral disc degeneration is the main contributor to low back pain, now the leading cause of disability worldwide. Gene transfer, either in a therapeutic attempt or in basic research to understand the mechanisms of disc degeneration, is a fascinating and promising tool to manipulate the complex physiology of the disc. Viral vectors based on the adeno-associated virus (AAV) have emerged as powerful transgene delivery vehicles yet a systematic investigation into their respective tropism, transduction efficiency, and relative toxicity have not yet been performed in the disc .

Single-cell RNA-seq identifies unique transcriptional landscapes of human nucleus pulposus and annulus fibrosus cells.

Intervertebral disc (IVD) disease (IDD) is a complex, multifactorial disease. While various aspects of IDD progression have been reported, the underlying molecular pathways and transcriptional networks that govern the maintenance of healthy nucleus pulposus (NP) and annulus fibrosus (AF) have not been fully elucidated. We defined the transcriptome map of healthy human IVD by performing single-cell RNA-sequencing (scRNA-seq) in primary AF and NP cells isolated from non-degenerated lumbar disc.

Correction: Sangadala, S. et al. FK506 Induces Ligand-Independent Activation of the Bone Morphogenetic Protein Pathway and Osteogenesis. 2019, , 1900.

The authors wish to make the following corrections to this paper [...

Network Analysis Identifies Gene Regulatory Network Indicating the Role of RUNX1 in Human Intervertebral Disc Degeneration.

Intervertebral disc (IVD) degeneration (IDD) is a multifactorial physiological process which is often associated with lower back pain. Previous studies have identified some molecular markers associated with disc degeneration, which despite their significant contributions, have provided limited insight into the etiology of IDD. In this study, we utilized a network medicine approach to uncover potential molecular mediators of IDD.

Derivation of notochordal cells from human embryonic stem cells reveals unique regulatory networks by single cell-transcriptomics.

Intervertebral disc degeneration (IDD) is a public health dilemma as it is associated with low back and neck pain, a frequent reason for patients to visit the physician. During IDD, nucleus pulposus (NP), the central compartment of intervertebral disc (IVD) undergo degeneration. Stem cells have been adopted as a promising biological source to regenerate the IVD and restore its function.

Rigid-Plating and Cortico-Cancellous Allograft Are Effective for 3-Level Anterior Cervical Discectomy and Fusion: Radiographic and Clinical Outcomes.

Objective: To determine the risk factors associated with radiographic changes and clinical outcomes following 3-level anterior cervical discectomy and fusion (ACDF) using rigidplate constructs and cortico-cancellous allograft. ACDF has demonstrated efficacy for treatment of multilevel degenerative cervical conditions, but current data exists in small heterogeneous forms.

Methods: A retrospective review included 98 patients with primary 3-level ACDF surgery at one institution from 2008 to 2013 with minimum 1-year follow-up.

FK506 Induces Ligand-Independent Activation of the Bone Morphogenetic Protein Pathway and Osteogenesis.

Osteoinductive bone morphogenetic proteins (BMPs), including BMP-2, have a unique capability of mediating bone formation both in orthotopic and ectopic locations. Immunosuppresive macrolides have been shown to potentiate BMP-2 activity through FKBP12, but these have yet to translate to effective osteoinductive therapies. Herein, we show the osteogenic activity of FK506 as a stand-alone agent in direct comparison to BMP-2 both in vitro and in vivo.

Sagittal spinopelvic malalignment in degenerative scoliosis patients: isolated correction of symptomatic levels and clinical decision-making.

Background: This study aims to determine if (1) loss of lumbar lordosis (LL), often associated with degenerative scoliosis (DS), is structural or rather largely due to positional factors secondary to spinal stenosis; (2) only addressing the symptomatic levels with a decompression and posterolateral fusion in carefully selected patients will result in improvement of sagittal malalignment; and (3) degree of sagittal plane correction achieved with such a local fusion could be predicted by routine pre-operative imaging.

Methods: A retrospective study design with prospectively collected imaging data of a consecutive series of surgically treated DS patients who underwent decompression and instrumented fusion at only symptomatic levels was performed. Pre- and post-operative plain radiographs and pre-operative magnetic resonance imaging (MRIs) of the spinopelvic region were analyzed.

There is no increased risk of adjacent segment disease at the cervicothoracic junction following an anterior cervical discectomy and fusion to C7.

Background Context: Anterior cervical discectomy and fusion (ACDF) is a very common operative intervention for the treatment of cervical spine degenerative disease in those who have failed non-operative measures. However, studies examining long-term follow-up on patients who underwent ACDF reveal evidence of radiographic and clinical degenerative disc disease at the levels adjacent to the fusion construct. Consistent with other junctional regions of the spine, the cervicothoracic junction (CTJ) has significant morphologic variations.

PDGF-BB inhibits intervertebral disc cell apoptosis in vitro.

Degeneration of the intervertebral disc (IVD) results in deterioration of the spinal motion segment and can lead to debilitating back pain. Given the established mitotic and anti-apoptotic effects of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in a variety of cell types we postulated that rhPDGF-BB might delay disc cell degeneration through inhibition of apoptosis. To address this hypothesis, we treated human IVD cells isolated from five independent patients with rhPDGF-BB in monolayer and 3D pellet cultures.

Management decisions for adolescent idiopathic scoliosis significantly affect patient radiation exposure.

Background Context: Adolescent idiopathic scoliosis (AIS) patients treated before the 1990s have a 1% to 2% increased lifetime risk of developing breast and thyroid cancer as a result of ionizing radiation from plain radiographs. Although present plain radiographic techniques have been able to reduce some of the radiation exposure, modern treatment algorithms for scoliosis often include computed tomography (CT) and intraoperative fluoroscopy. The exact magnitude of exposure to ionizing radiation in adolescents during modern scoliosis treatment is therefore unclear.

Mean subaxial space available for the cord index as a novel method of measuring cervical spine geometry to predict the chronic stinger syndrome in American football players.

Object: The chronic stinger syndrome is a distinct entity from acute stingers and has been shown to have its own pathophysiology that, unlike acute stingers, may reflect long-standing geometrical changes of the subaxial spinal canal and chronic irritation/degeneration of the exiting nerve root complex. There is no method available, however, to accurately predict these symptoms in athletes. The mean subaxial cervical space available for the cord (MSCSAC) is a novel alternative to the Torg ratio for predicting neurological symptoms caused by cervical spondylosis in elite athletes.