To determine whether spinal facet osteoblasts at the curve apex display a different phenotype to osteoblasts from outside the curve in patients with adolescent idiopathic scoliosis (AIS). Intrinsic differences in the phenotype of spinal facet bone tissue and in spinal osteoblasts have been implicated in the pathogenesis of AIS. However, no study has compared the phenotype of facet osteoblasts at the curve apex with the facet osteoblasts from outside the curve in patients with AIS. Facet bone tissue was collected from three sites, the concave and convex side at the curve apex and from outside the curve from three female patients with AIS (aged 13–16 years). Micro-CT analysis was used to determine the density and trabecular structure. Osteoblasts were then cultured from the sampled bone. Osteoblast phenotype was investigated by assessing cellular proliferation (MTS assay), cellular metabolism (alkaline phosphatase and Seahorse Analyser), bone nodule mineralisation (Alizarin red assay), and the mRNA expression of Wnt signalling genes (quantitative RT-PCR). Convex bone showed greater bone mineral density and trabecular thickness than did concave bone. The convex side of the curve apex exhibited a significantly higher proliferative and metabolic phenotype and a greater capacity to form mineralised bone nodules than did concave osteoblasts. mRNA expression of SKP2 was significantly greater in both concave and convex osteoblasts than in non-curve osteoblasts. The expression of SFRP1 was significantly downregulated in convex osteoblasts compared with either concave or non-curve. Intrinsic differences that affect osteoblast function are exhibited by spinal facet osteoblasts at the curve apex in patients with AIS

Aims. Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs). Methods. Immunohistochemical staining was performed to observe the expression of A20 in normal and degenerated human intervertebral discs. The NPCs were dissected from the tail vertebrae of healthy male Sprague-Dawley rats and were cultured in the incubator. In the experiment, TNF-α was used to mimic the inflammatory environment of IDD. The cell viability and senescence were examined to investigate the effect of A20 on TNF-α-treated NPCs. The expression of messenger RNA (mRNA)-encoding proteins related to matrix macromolecules (collagen II, aggrecan) and senescence markers (p53, p16). Additionally, NF-κB/p65 activity of NPCs was detected within different test compounds. Results. The expression of A20 was upregulated in degenerate human intervertebral discs. The A20 levels of NPCs in TNF-α inflammatory microenvironments were dramatically higher than those of the control group. TNF-α significantly decreased cell proliferation potency but increased senescence-associated beta-galactosidase (SA-β-Gal) activity, the expression of senescence-associated proteins, the synthesis of extracellular matrix, and G1 cycle arrest. The senescence indicators and NF-κB/p65 expression of A20 downregulated group treated with TNF-α were significantly upregulated compared to TNF-α-treated normal NPCs. Conclusion. A20 has a self-protective effect on the senescence of NPCs induced by TNF-α. The downregulation of A20 in NPCs exacerbated the senescence of NPCs induced by TNF-α. Cite this article:Bone Joint Res. 2020;9(5):225–235

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Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

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Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.

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This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect.

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The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS).

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This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

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In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

Introduction. Type 1 neurofibromatosis is a serious hereditary disease in which mainly skin, nervous, muscular, and bone systems are damaged. In bone systems the most common deformities are thoracic kyphosis and scoliosis. Data for morphological changes in the structural components of spine in neurofibromatosis are scarce. Thus our study aimed to investigate morphological changes in structural components of the spine in NF1 neurofibromatosis. Methods. Growth plates, intervertebral discs, and fragments of vertebral bodies from deformed and adjacent segments of the spine were obtained from 15 patients aged 10–14 years with scoliosis (Cobb angle 90–120°) caused by neurofibromatosis. Preoperative examination included MRI study of the spine and brain to exclude intracanal masses, and radiographic study of the spine. Patients did not present any neurological symptoms. All children underwent anterior release and interbody fusion. Structural spinal components from children aged 12–14 years collected at forensic autopsy were used as controls. Tissues were investigated by conventional histochemical and ultrastructural methods. The levels of aggrecan and NF1 gene expression were studied with the PCR method. Results. The study of growth plate and intervertebral disc specimens removed during surgery for scoliosis in neurofibromatosis showed a clear boundary between their convex and concave sides. Both growth plate and intervertebral disc in convex side retain their architectonic and histochemical characteristics. The concave side of the growth plate is presented by small chondroblasts densely spaced without a definite orientation and surrounded by homogeneous matrix, which is made up of chondroitin sulphates. These embryonic-type chondroblasts are poorly differentiated. Chondroblasts proliferate beyond the growth plate. Proliferating cells invade into vertebral body and are bordered by thin bone lamellae, causing the scalloping of vertebral body as a radiological symptom of the pathology. Changes occurring in the intervertebral disc are of considerable interest. Concave-side disc is characterised by isolated proliferation zones containing poorly differentiated chondroblasts and fibroblasts, and neurinoma-like masses. Bone trabeculae inside a concave-side vertebra are passing the stage of osteogenesis imperfecta. Detected morphological changes in spinal structures are consistent with findings of Stevenson, who registered cartilage and bone deficiencies in animal model (mice with NF1 genemutation). Thus, morphological studies testify to structural disorder in concave side of the growth plate, but unchanged regularities and stages of chondroblast differentiation and adequate osteogenesis in the convex side. NF1 gene regulates the growth, differentiation, and proliferation of chondroblasts at the early stage of embryogenesis. Gene inactivation at a somite stage results in altered development of definitive spinal structures. Continued growth with adequate proliferation, differentiation, osteogenesis, and topochemical characteristics occurs in the convex-side growth plate, and growth disorder in the concave-side part with continued load cause growth asymmetry and development of spinal deformity. Scoliosis associated with neurofibromatosis is notable for deformity progression and pseudoarthrosis development after surgery. Deformity progression (modulation) should be considered in connection with disorder in osteogenic potency of osteoblasts. Conclusions. The causal factor of spinal deformity development in NF1 neurofibromatosis is NF1 gene mutation. Inactivation of NF1 gene results in disorder in chondrogenesis and osteogenesis within structurally altered zones. A continued load causes development of scoliotic spinal deformity

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Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

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The aim of this study was to determine whether there is an increased prevalence of scoliosis in patients who have suffered from a haematopoietic malignancy in childhood.

To evaluate and describe the plain radiographic changes observed with time in fusions using SiS-CaP. We describe, for the first time, 4 stages of bone substitute fusion mass (BSFM) radiographic appearance in relation to time post-op. Retrospective, radiological evaluation. Over 200 plain radiographs were evaluated. 70 consecutive fusions for degenerative spinal stenosis were included, in all cases performed by the same surgeon using the same operative technique. Follow-up was from 3 months to 2 years post-op. Radiographs were evaluated for the presence or absence of SiS-CaP granules, bone formation and for evidence of pseudarthrosis. Trends were seen within the BSFM with respect to time. At 6-12 weeks post-op a ‘homogenous granular stage’ indicates the presence of the unchanged SiS-CaP. At 12 weeks, small pockets appear within the BSFM in the ‘vacuolation stage’, indicating bioresorption of the graft. Vacuoles become increasingly radio-opaque indicating bone proliferation during the ‘homogenous lamellar stage’. At variable time between 6 months and 2 years, the BSFM becomes encapsulated in the ‘cortication stage’ visible as a sclerotic rim around the BSFM. We have seen a clear trend in the behaviour of the fusion mass in this case series. The radiological stages we have described above can be closely correlated with previously reported in-vitro and in-vivo studies looking at the micro-function of SiS-CaP. We hope that this description will help to judge the progress of graft incorporation and fusion. Further study of inter and intra-observer correlation will be required

Introduction. Although the association between osteoporosis and adolescent idiopathic scoliosis (AIS) has become widely accepted, the mechanism behind the development of osteoporosis and AIS remains unknown. To elucidate this relationship, we investigated the radiological and histological changes in a model of scoliosis in chickens, focusing on the cervical vertebrae that are not affected by scoliosis. Methods. 40 newly hatched broiler chickens were divided randomly into four equal groups: sham-operated chickens serving as control (CNT); pinealectomised chickens (PNX); and sham-operated (CNT+MLT) and pinealectomized chickens (PNX+MLT) that received intraperitoneal administration of MLT (8 mg/kg) at 2200 h daily. Pinealectomies were done at the age of 3 days. Before killing the chickens at 2 months of age, blood samples were collected at midnight and MLT concentrations were measured by radioimmunoassay. Post-mortem radiographs were examined for the presence of scoliosis, and microcomputed tomography (micro-CT) images were taken to assess the microstructure of the cervical vertebrae. Histological specimens of the scanned cervical vertebra were prepared, and a mid-sagittal section was stained with haematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) to assess the numbers of osteoblasts and osteoclasts, respectively. Results. Scoliosis developed at the thoracic spine in all chickens in the PNX group and in two of the PNX+MLT group. MLT concentrations in the PNX group were substantially reduced, whereas normal concentrations were restored in the PNX+MLT group and were normal in the CNT and CNT+MLT groups. Micro-CT data showed that chickens in the PNX group had a greater degree of generalised osteoporosis than did those in the other groups. The number of osteoblasts was significantly decreased in the PNX group, whereas we recorded no significant difference between the CNT, CNT+MLT, and PNX+MLT groups. The number of osteoclasts was similar in all groups. Conclusions. Our results suggest that MLT deficiency reduces osteoblast proliferation and leads to the development of scoliosis and osteoporosis. The restoration of MLT prevented the development of scoliosis and osteoporosis, indicating that MLT concentrations might be crucial to the development of scoliotic deformity and osteoporosis in AIS

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Pulsed electromagnetic field (PEMF) stimulation was evaluated after anterior cervical discectomy and fusion (ACDF) procedures in a randomized, controlled clinical study performed for United States Food and Drug Administration (FDA) approval. PEMF significantly increased fusion rates at six months, but 12-month fusion outcomes for subjects at elevated risk for pseudoarthrosis were not thoroughly reported. The objective of the current study was to evaluate the effect of PEMF treatment on subjects at increased risk for pseudoarthrosis after ACDF procedures.

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation.

New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP.