NELL-1

UNLABELLED: Sarcomas produce an abnormal extracellular matrix (ECM), which in turn provides instructive cues for cell growth and invasion. Neural EGF like-like molecule 1 (NELL1) is a secreted glycoprotein characterized by its nonneoplastic osteoinductive effects, yet it is highly expressed in skeletal sarcomas. Here, we show that genetic deletion of NELL1 markedly reduces invasive behavior across human osteosarcoma (OS) cell lines. NELL1 deletion resulted in reduced OS disease progression, inhibiting metastasis and improving survival in a xenograft mouse model...

NELL1 (Neural epidermal growth factor-like (EGFL)-like protein) is an important biomarker associated with tissue and bone development and regeneration. NELL1 upregulation has been linked with metastasis and negative prognosis in rhabdomyosarcoma (RMS). Furthermore, multiple recent studies have also shown the importance of NELL1 in inflammatory bowel disease and membranous nephropathy, amongst other diseases. In this study, several anti-NELL1 DNA aptamers were selected from a randomized ssDNA pool using a fluorescence-guided method and evaluated for their binding affinity and selectivity...

Objective: With the advances in biological technologies over the past 20 years, a number of new therapies to promote bone healing have been introduced. Particularly in the spinal surgery field, more unprecedented biological therapeutics become available to enhance spinal fusion success rate along with advanced instrumentation approaches. Yet surgeons may not have been well informed about their safety and efficacy profiles in order to improve clinical practices. Therefore there is a need to summarize the evidence and bring the latest progress to surgeons for better clinical services for patients...

Neural epidermal growth factor-like (EGFL)-like protein (NELL)-1 is a potent and key osteogenic factor in the development and regeneration of skeletal tissues. Intriguingly, accumulative data from genome-wide association studies (GWASs) have started unveiling potential broader roles of NELL-1 beyond its functions in bone and cartilage. With exploration of the genetic variants of the entire genome in large-scale disease cohorts, GWASs have been used for establishing the connection between specific single-nucleotide polymorphisms of NELL1, in addition to osteoporosis, metabolic diseases, inflammatory conditions, neuropsychiatric diseases, neurodegenerative disorders, and malignant tumors...

Novel bone regeneration strategies often show promise in rodent models yet are unable to successfully translate to clinical therapy. Sheep, goats, and dogs are used as translational models in preparation for human clinical trials. While human MSCs (hMSCs) undergo osteogenesis in response to well-defined protocols, canine MSCs (cMSCs) are more incompletely characterized. Prior work suggests that cMSCs require additional agonists such as IGF-1, NELL-1, or BMP-2 to undergo robust osteogenic differentiation in vitro ...

OBJECTIVE: This study aims to construct a composite system of the tri-block polyethylene glycol injectable hydrogel (3B-PEG IH) and Neural epithelial growth factor-like Protein 1 (Nell-1), and to analyze its therapeutic effect on temporomandibular joint osteoarthritis (TMJOA)。 Methods: Sol-gel transition temperature was measured via inverting test. The viscoelastic modulus curves was measured by Rheometer. Degradation and controlled release profiles of 3B-PEG IH were drawn by incubated in PBS...

Background: Currently, several specific antigens, M-type receptor for secretory phospholipase A2(PLA2R1), thrombospondin type-1 domain-containing 7A(THSD7A), and neural epidermal growth factor-like 1 protein (NELL-1), are discovered associated with the onset of idiopathic membranous nephropathy (IMN). But the pathomechanisms of IMN still need to be further claried. Understanding the mechanisms of IMN is required to improve its diagnosis and treatment. Methods: In this study, we constructed miRNA regulatory networks to investigate IMN development...

INTRODUCTION: mRNA COVID-19 vaccine is more effective than traditional vaccines owing to superior immune activation. Nevertheless, the impact of mRNA COVID-19 vaccine on triggering de novo /relapsing glomerulonephritis (GN) is limited. We report a case series of patients who developed new or relapsing GN postvaccination. METHODS: We evaluated baseline characteristics, vaccine type, and clinical outcomes of 13 patients from our institution who had a new diagnosis or relapse of their GN post-mRNA COVID-19 vaccination...

An important objective of vascularized tissue regeneration is to develop agents for osteonecrosis. We aimed to identify the pro-angiogenic and osteogenic efficacy of adipose tissue-derived (AD) pericytes combined with Nel-like protein-1 (NELL-1) to investigate the therapeutic effects on osteonecrosis. Tube formation and cell migration were assessed to determine the pro-angiogenic efficacy. Vessel formation was evaluated in vivo using the chorioallantoic membrane assay. A mouse model with a 2.5 mm necrotic bone fragment in the femoral shaft was used as a substitute for osteonecrosis in humans...

Introduction: This work aimed to reveal the crucial role of Nell-1 in the angiogenic differentiation of human dental pulp stem cells (DPSCs) alone or co-cultured with human umbilical vein endothelial cell (HUVECs) in vitro and whether this molecule is involved in the pulp exposure model in vivo . Methods: Immunofluorescence was conducted to ascertain the location of Nell-1 on DPSCs, HUVECs, and normal rat dental tissues. RT-PCR, Western blot, and ELISA were performed to observe the expression levels of angiogenic markers and determine the angiogenic differentiation of Nell-1 on DPSCs alone or co-cultured with HUVECs, as well as in vitro tube formation assay...

Tubular basement membrane (TBM) deposits are very uncommon in non-lupus membranous nephropathy. We report 5 patients with membranous nephropathy and extensive TBM deposits following allogeneic hematopoietic cell transplant. Patients presented with nephrotic syndrome (3 also had acute kidney injury) late post-transplant in association with chronic graft-versus-host disease (cGVHD). Kidney biopsies revealed global subepithelial and extensive TBM immune complex deposits, accompanied by acute tubular injury (n = 4) and tubulointerstitial inflammation (n = 4)...

OBJECTIVES: This study aimed to explore the regulatory mechanism of methyltransferase3 (METTL3) -mediated long non-coding RNA (lncRNA) N6-methyladenosine (m6 A) modification in the osteogenic differentiation of human adipose-derived stem cells (hASCs) induced by NEL-like 1 protein (NELL-1). MATERIALS AND METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and high- throughput sequencing for RNA (RNA-seq) were performed on hASCs. Osteogenic ability was detected by alkaline phosphatase (ALP) staining, Alizarin Red S(ARS) staining, ALP quantification and Quantitative real-time polymerase chain reaction analysis (qRT-PCR)...

INTRODUCTION: In endochondral ossification septoclasts and osteoclasts (also called chondroclasts) release growth factors deposited in non-calcified and calcified zones of the growth plate. They stimulate, within the metaphysis, initial stages of the bone formation. We have recently reported quantitation of several growth factors in calcified cartilage from calf costochondral junction. Data from the analogous human cartilage could possibly help to choose efficient combinations of growth factors for clinical applications, but the amount of the calcified cartilage needed for analysis of numerous growth factors would be difficult to collect...

Background: As commonly bone defect is a disease of jaw that can seriously affect implant restoration, the bioactive scaffold can be used as potential systems to provide effective repair for bone defect. Purpose: A osteoinductive bone tissue engineering scaffold has been prepared in order to explore the effect of bioactive materials on bone tissue engineering. Methods: In this study, NELL-1 nanoparticles (Chi/NNP) and nano hydroxyapatite were incorporated in composite scaffolds by electrospinning and characterized using TEM, SEM, contact angle, tensile tests and in vitro drug release...

Background and objectives: NELL-1 is a competent growth factor and it reported to target cells committed to the osteochondral lineage. The secreted, osteoinductive glycoproteins are reported to rheostatically control skeletal ossification. This study was performed to determine the effects of NELL-1 on spheroid morphology and cell viability and the promotion of osteogenic differentiation of stem cell spheroids. Materials and Methods: Cultures of stem cell spheroids of gingiva-derived stem cells were grown in the presence of NELL-1 at concentrations of 1, 10, 100, and 500 ng/mL...

Nephrotic syndrome is in adult patients mainly due to membranous nephropathy (MN) characterized by thickening of the glomerular basement membrane (GBM) and immune complex formation between podocytes and the GBM. Autoantibodies directed against the M-type phospholipase A2 receptor (PLA2R) and thrombospondin 1 domain-containing 7 A (THSD7A) can be used as diagnostic biomarkers. THSD7A seems to be of direct pathogenic significance as is suggested by experimental models and plasmapheresis in humans. Recently, further antigens like NELL-1 (neural tissue encoding protein with EGF-like repeats-1), exostosin 1 and 2 have been discovered...

Nel-like molecule type 1 (Nell-1) is a secreted protein that plays an important role in osteoinduction in multiple animal models. A previous study has suggested the anti-inflammatory effect of Nell-1 on bone inflammation inhibition. However, its role in pulpitis has not been investigated. The present study aims to explore the effect of human recombinant Nell-1 (Nell-1) on rat pulp inflammation response, and its effect on lipopolysaccharide-induced inflammation in human dental pulp cells and its related intracellular signaling pathways...

Endochondral bone formation is orchestrated by growth factors produced by chondrocytes and deposited in the cartilage matrix. Whilst some of these factors have been identified, the complete list and their relationship remains unknown. In the present study, the growth factors were isolated from non-calcified and calcified cartilage of costochondral junctions. Cartilage dissected from the ribs of 6-20-week-old calves was purchased from a local butcher within 24 h of the death of the animal. The isolation involved hyaluronidase digestion, guanidinium hydrochloride (GuHCl) extraction, HCl decalcification and GuHCl extraction of the decalcified matrix...

BACKGROUND AND OBJECTIVES: The neural EGF-like 1 (NELL-1) protein is a novel antigen in primary membranous nephropathy. The prevalence and clinical characteristics of NELL-1-positive membranous nephropathy in Chinese individuals with primary membranous nephropathy are unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 832 consecutive patients with biopsy-proven primary membranous nephropathy were enrolled. The glomerular expression of phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A) was screened...

The discovery of anti-podocyte antibodies in primary membranous nephropathy (MN) has revolutionized our approach toward the diagnosis and treatment of this disease. Evaluation of serum levels of anti-podocyte antibodies paved the way for non-invasive diagnosis and helped distinguish between primary and secondary MN although the relationship between anti-podocyte antibodies and cancer remains to be elucidated. Serum levels of anti-PLA2R antibodies directed against the major podocyte autoantigen are related to MN activity and the decrease in serum levels of anti-PLA2R antibodies in response to treatment (immunologic remission) also serves as an early indicator of the later putative proteinuric remission, enabling personalization of the treatment...