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NELL-1

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https://www.readbyqxmd.com/read/29388706/nell-1-%C3%AE-e-a-novel-transcript-of-nell-1-inhibits-cell-migration-by-interacting-with-enolase-1
#1
Huaxiang Zhao, Xueyan Qin, Qian Zhang, Xinli Zhang, Jiuxiang Lin, Kang Ting, Feng Chen
NELL-1 is a secreted protein that was originally found to be upregulated in pathologically fusing and fused sutures in non-syndromic unilateral coronal synostosis patients. Apart from the ability of NELL-1 to promote osteogenesis in long and craniofacial bones, NELL-1 reportedly inhibits the formation of several benign and malignant tumors. We previously identified a novel transcript of Nell-1 that lacked a calcium-binding epidermal growth factor (EGF)-like domain compared with full-length Nell-1; this new transcript was named Nell-1-ΔE...
February 1, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29316655/nfatc1-is-a-functional-transcriptional-factor-mediating-nell-1-induced-runx3-upregulation-in-chondrocytes
#2
Chenshuang Li, Zhong Zheng, Xinli Zhang, Greg Asatrian, Eric Chen, Richard Song, Cymbeline Culiat, Kang Ting, Chia Soo
Neural EGFL like 1 (Nell-1) is essential for chondrogenic differentiation, maturation, and regeneration. Our previous studies have demonstrated that Nell-1's pro-chondrogenic activities are predominantly reliant upon runt-related transcription factor 3 (Runx3)-mediated Indian hedgehog (Ihh) signaling. Here, we identify the nuclear factor of activated T-cells 1 (Nfatc1) as the key transcriptional factor mediating the Nell-1 → Runx3 signal transduction in chondrocytes. Using chromatin immunoprecipitation assay, we were able to determine that Nfatc1 binds to the -833--810 region of the Runx3 -promoter in response to Nell-1 treatment...
January 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29288032/chitosan-stablized-bovine-serum-albumin-nanoparticles-having-ability-to-control-the-release-of-nell-1-protein
#3
Yourui Li, Hualei Song, Shijiang Xiong, Tian Tian, Tongbin Liu, Yuanyuan Sun
The study was designed to prepare and evaluate chitosan stabilized-albumin nanoparticles as NELL-1 protein carriers(Chi/NNPs). The Chi/NNPs were prepared by desolvation method and then stabilized by chitosan through electrostatic interaction. The Chi/NNPs were characterized for drug loading efficiency, surface morphology, particle size, surface charge. Fluorescein isothiocyanate-labeled chitosan was used to confirm the homogeneity of chitosan coating on the BSA nanoparticles. The NELL-1 bioactivity of Chi/NNPs and the release kinetics were investigated in vitro...
April 1, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29276737/neural-egf-like-protein-1-nell-1-signaling-crosstalk-in-mesenchymal-stem-cells-and-applications-in-regenerative-medicine
#4
Mikhail Pakvasa, Alex Alverdy, Sami Mostafa, Eric Wang, Lucy Fu, Alexander Li, Leonardo Oliveira, Aravind Athiviraham, Michael J Lee, Jennifer Moriatis Wolf, Tong-Chuan He, Guillermo A Ameer, Russell R Reid
Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects, two problems associated with significant morbidity. The differentiation of mesenchymal stem cells into the osteogenic lineage requires a specific microenvironment and certain osteogenic growth factors. Neural EGF Like-Like molecule 1 (NELL-1) is a secreted glycoprotein that has proven, both in vitro and in vivo , to be a potent osteo-inductive factor. Furthermore, it has been shown to repress adipogenic differentiation and inflammation...
September 2017: Genes & Diseases
https://www.readbyqxmd.com/read/29137952/neural-egfl-like-1-regulates-cartilage-maturation-through-runt-related-transcription-factor-3-mediated-indian-hedgehog-signaling
#5
Chenshuang Li, Zhong Zheng, Jie Jiang, Wenlu Jiang, Kevin Lee, Emily A Berthiaume, Eric C Chen, Cymbeline T Culiat, Yan-Heng Zhou, Xinli Zhang, Kang Ting, Chia Soo
The pro-chondrogenic function of runt-related transcription factor 2 (Runx2) was previously considered to be dependent on direct binding with the promoter of Indian hedgehog (Ihh)-the major regulator of chondrocyte differentiation, proliferation, and maturation. The authors' previous studies identified neural EGFL like 1 (Nell-1) as a Runx2-responsive growth factor for chondrogenic differentiation and maturation. In this study, it was further revealed that the pro-chondrogenic activities of Nell-1 also rely on Ihh signaling, by showing: i) Nell-1 significantly elevated Ihh signal transduction; ii) Nell-1 deficiency markedly reduced Ihh activation in chondrocytes; and iii) Nell-1-stimulated chondrogenesis was significantly reduced by the specific hedgehog inhibitor cyclopamine...
February 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/28629047/two-phase-electrospinning-to-incorporate-growth-factors-loaded-chitosan-nanoparticles-into-electrospun-fibrous-scaffolds-for-bioactivity-retention-and-cartilage-regeneration
#6
Chongyang Wang, Wenxiu Hou, Xuran Guo, Juehong Li, Tu Hu, Manle Qiu, Shen Liu, Xiumei Mo, Xudong Liu
Growth factor is an essential ingredient to regulate mesenchymal stem cells (MSCs) chondrogenic differentiation in cartilage tissue engineering. However, non-osteochondral specification, short plasma half time and bioactivity loss restrict growth factor's application. Thus, novel chondrogenic growth factors, specifically target osteochondral lineage cells, that can be sustained release and bioactivity protected to exert functions continually and effectively have attracted increasing researchers' interest. To achieve these goals, chitosan nanoparticles and electrospun fiber scaffolds were used as dual release system to sustain release Nel-like molecule-1 (Nell-1) growth factor and protect bioactivity, then the effect and mechanism of Nell-1 on inducing human bone MSCs (hBMSCs) differentiate toward chondrocytes were investigated...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28614787/nell-1-induces-sca-1-mesenchymal-progenitor-cell-expansion-in-models-of-bone-maintenance-and-repair
#7
Aaron W James, Jia Shen, Rebecca Tsuei, Alan Nguyen, Kevork Khadarian, Carolyn A Meyers, Hsin Chuan Pan, Weiming Li, Jin H Kwak, Greg Asatrian, Cymbeline T Culiat, Min Lee, Kang Ting, Xinli Zhang, Chia Soo
NELL-1 is a secreted, osteogenic protein first discovered to control ossification of the cranial skeleton. Recently, NELL-1 has been implicated in bone maintenance. However, the cellular determinants of NELL-1's bone-forming effects are still unknown. Here, recombinant human NELL-1 (rhNELL-1) implantation was examined in a clinically relevant nonhuman primate lumbar spinal fusion model. Prolonged rhNELL-1 protein release was achieved using an apatite-coated β-tricalcium phosphate carrier, resulting in a local influx of stem cell antigen-1-positive (Sca-1+) mesenchymal progenitor cells (MPCs), and complete osseous fusion across all samples (100% spinal fusion rate)...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514897/biomaterials-and-bioactive-agents-in-spinal-fusion
#8
Rui M Duarte, Pedro Varanda, Rui L Reis, Ana Rita C Duarte, Jorge Correia-Pinto
Management of degenerative spine pathologies frequently leads to the need for spinal fusion (SF), where bone growth is induced toward stabilization of the interventioned spine. Autologous bone graft (ABG) remains the gold-standard inducer, whereas new bone graft substitutes attempt to achieve effective de novo bone formation and solid fusion. Limited fusion outcomes have driven motivation for more sophisticated and multidisciplinary solutions, involving new biomaterials and/or biologics, through innovative delivery platforms...
December 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28489940/isolation-and-characterization-of-canine-perivascular-stem-stromal-cells-for-bone-tissue-engineering
#9
Aaron W James, Xinli Zhang, Mihaela Crisan, Winters R Hardy, Pei Liang, Carolyn A Meyers, Sonja Lobo, Venu Lagishetty, Martin K Childers, Greg Asatrian, Catherine Ding, Yu-Hsin Yen, Erin Zou, Kang Ting, Bruno Peault, Chia Soo
For over 15 years, human subcutaneous adipose tissue has been recognized as a rich source of tissue resident mesenchymal stem/stromal cells (MSC). The isolation of perivascular progenitor cells from human adipose tissue by a cell sorting strategy was first published in 2008. Since this time, the interest in using pericytes and related perivascular stem/stromal cell (PSC) populations for tissue engineering has significantly increased. Here, we describe a set of experiments identifying, isolating and characterizing PSC from canine tissue (N = 12 canine adipose tissue samples)...
2017: PloS One
https://www.readbyqxmd.com/read/28463604/nell-1-hmgb1-and-ccn2-enhance-migration-and-vasculogenesis-but-not-osteogenic-differentiation-compared-to-bmp2
#10
Shorouk Fahmy-Garcia, Marjolein van Driel, Janneke Witte-Buoma, Heike Walles, Johannes P T M van Leeuwen, Gerjo J V M van Osch, Eric Farrell
Currently, autografts still represent the gold standard treatment for the repair of large bone defects. However, these are associated with donor-site morbidity and increased pain, cost, and recovery time. The ideal therapy would use biomaterials combined with bone growth factors to induce and instruct bone defect repair without the need to harvest patient tissue. In this line, bone morphogenetic proteins (BMPs) have been the most extensively used agents for clinical bone repair, but at supraphysiological doses that are not without risk...
February 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28302495/neural-egfl-like-1-is-a-downstream-regulator-of-runt-related-transcription-factor-2-in-chondrogenic-differentiation-and-maturation
#11
Chenshuang Li, Jie Jiang, Zhong Zheng, Kevin S Lee, Yanheng Zhou, Eric Chen, Cymbeline T Culiat, Yiqiang Qiao, Xuepeng Chen, Kang Ting, Xinli Zhang, Chia Soo
Recent studies indicate that neural EGFL-like 1 (Nell-1), a secretive extracellular matrix molecule, is involved in chondrogenic differentiation. Herein, we demonstrated that Nell-1 serves as a key downstream target of runt-related transcription factor 2 (Runx2), a central regulator of chondrogenesis. Unlike in osteoblast lineage cells where Nell-1 and Runx2 demonstrate mutual regulation, further studies in chondrocytes revealed that Runx2 tightly regulates the expression of Nell-1; however, Nell-1 does not alter the expression of Runx2...
May 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28198775/combining-smoothened-agonist-and-nel-like-protein-1-enhances-bone-healing
#12
Soonchul Lee, Chenchao Wang, Hsin Chuan Pan, Swati Shrestha, Carolyn Meyers, Catherine Ding, Jia Shen, Eric Chen, Min Lee, Chia Soo, Kang Ting, Aaron W James
BACKGROUND: Nonhealing bone defects represent an immense biomedical burden. Despite recent advances in protein-based bone regeneration, safety concerns over bone morphogenetic protein-2 have prompted the search for alternative factors. Previously, the authors examined the additive/synergistic effects of hedgehog and Nel-like protein-1 (NELL-1) on the osteogenic differentiation of mesenchymal stem cells in vitro. In this study, the authors sought to leverage their previous findings by applying the combination of Smoothened agonist (SAG), hedgehog signal activator, and NELL-1 to an in vivo critical-size bone defect model...
June 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27585207/polyelectrolyte-complex-for-heparin-binding-domain-osteogenic-growth-factor-delivery
#13
Raymond Wing Moon Lam, Sunny Akogwu Abbah, Wang Ming, Mathanapriya Naidu, Felly Ng, Hu Tao, James Goh Cho Hong, Kang Ting, Wong Hee Kit
During reconstructive bone surgeries, supraphysiological amounts of growth factors are empirically loaded onto scaffolds to promote successful bone fusion. Large doses of highly potent biological agents are required due to growth factor instability as a result of rapid enzymatic degradation as well as carrier inefficiencies in localizing sufficient amounts of growth factor at implant sites. Hence, strategies that prolong the stability of growth factors such as BMP-2/NELL-1, and control their release could actually lower their efficacious dose and thus reduce the need for larger doses during future bone regeneration surgeries...
August 22, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27354930/efficacy-of-intraperitoneal-administration-of-pegylated-nell-1-for-bone-formation
#14
Justine Tanjaya, Yulong Zhang, Soonchul Lee, Jiayu Shi, Eric Chen, Pia Ang, Xinli Zhang, Sotirios Tetradis, Kang Ting, Benjamin Wu, Chia Soo, Jin Hee Kwak
Systemically delivered NEL-like molecule-1 (NELL-1), a potent pro-osteogenic protein, promotes bone formation in healthy and osteoporotic mouse models. PEGylation of NELL-1 (NELL-PEG) increases the half-life of the protein in a mouse model without compromising its osteogenic potential, thereby improving its pharmacokinetics upon systemic delivery. This study consists of a twofold approach: a biodistribution test and an in vivo osteogenic potential test. The biodistribution test compared two commonly used administration methods for drug delivery other than intravenous-intraperitoneal (IP) and subcutaneous (SC)-to examine NELL-PEG biodistribution in mice...
2016: BioResearch Open Access
https://www.readbyqxmd.com/read/27349789/controlled-release-of-nell-1-protein-from-chitosan-hydroxyapatite-modified-tcp-particles
#15
Yulong Zhang, Rui Dong, Yujin Park, Marc Bohner, Xinli Zhang, Kang Ting, Chia Soo, Benjamin M Wu
NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP)...
September 10, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27113550/vertebral-implantation-of-nell-1-enhances-bone-formation-in-an-osteoporotic-sheep-model
#16
Aaron W James, Michael Chiang, Greg Asatrian, Jia Shen, Raghav Goyal, Choon G Chung, Le Chang, Swati Shrestha, A Simon Turner, Howard B Seim, Xinli Zhang, Benjamin M Wu, Kang Ting, Chia Soo
BACKGROUND: Vertebral compression fractures related to osteoporosis greatly afflict the aging population. One of the most commonly used therapy today is balloon kyphoplasty. However, this treatment is far from ideal and is associated with significant side effects. NELL-1, an osteoinductive factor that possesses both pro-osteogenic and anti-osteoclastic properties, is a promising candidate for an alternative to current treatment modalities. This study utilizes the pro-osteogenic properties of recombinant human NELL-1 (rhNELL-1) in lumbar spine vertebral defect model in osteoporotic sheep...
June 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27080300/-nell-1-a-novel-highly-efficient-and-specific-growth-factor
#17
REVIEW
X Y Qin, H X Zhao, Q Zhang, F Chen, J X Lin
Regeneration of bone tissue, as well as other tissues, requires involvement and interaction of cells, scaffolds and relevant growth factors, among which growth factors play a crucial role in maintaining the stability of microenvironment. Nel-like-type 1 molecule (NELL-1), a novel growth factor in tissue engineering, has been studied intensively in recent years. Researches mainly covered gene and protein structure and their expression profiling, biological function, molecular mechanisms and disease relevance...
April 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27047227/nell-1-expression-in-tumors-of-cartilage
#18
Jia Shen, Gregory LaChaud, Swati Shrestha, Greg Asatrian, Xinli Zhang, Sarah M Dry, Chia Soo, Kang Ting, Aaron W James
BACKGROUND/AIMS: NELL-1 is a novel osteochondral differentiation factor protein with increasing usage in tissue engineering. Previously, we reported the expression patterns of NELL-1 in bone-forming skeletal tumors. With increasing interest in the use of NELL-1 protein, we sought to examine the expression of NELL-1 in cartilage-forming tumors. METHODS: Immunohistochemical expression was examined in human pathologic specimens. RESULTS: Consistent NELL-1 overexpression across all cartilage-forming tumors was observed...
December 2015: Journal of Orthopaedics
https://www.readbyqxmd.com/read/26772960/novel-wnt-regulator-nel-like-molecule-1-antagonizes-adipogenesis-and-augments-osteogenesis-induced-by-bone-morphogenetic-protein-2
#19
Jia Shen, Aaron W James, Xinli Zhang, Shen Pang, Janette N Zara, Greg Asatrian, Michael Chiang, Min Lee, Kevork Khadarian, Alan Nguyen, Kevin S Lee, Ronald K Siu, Sotirios Tetradis, Kang Ting, Chia Soo
The differentiation factor NEL-like molecule-1 (NELL-1) has been reported as osteoinductive in multiple in vivo preclinical models. Bone morphogenetic protein (BMP)-2 is used clinically for skeletal repair, but in vivo administration can induce abnormal, adipose-filled, poor-quality bone. We demonstrate that NELL-1 combined with BMP2 significantly optimizes osteogenesis in a rodent femoral segmental defect model by minimizing the formation of BMP2-induced adipose-filled cystlike bone. In vitro studies using the mouse bone marrow stromal cell line M2-10B4 and human primary bone marrow stromal cells have confirmed that NELL-1 enhances BMP2-induced osteogenesis and inhibits BMP2-induced adipogenesis...
February 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/26700847/accelerated-chondrogenic-differentiation-of-human-perivascular-stem-cells-with-nell-1
#20
Chen-Shuang Li, Xinli Zhang, Bruno Péault, Jie Jiang, Kang Ting, Chia Soo, Yan-Heng Zhou
Osteoarthritis is the leading cause of disability in the US. Consequently, there is a pressing need for restoring the structural and functional properties of diseased articular cartilage. Yet the search for the right combination of proper target cells and growth factors for cartilage regeneration remains challenging. In this study, we first tested the intrinsic chondrogenic differentiation ability of human perivascular stem cells (hPSCs), a novel source of mesenchymal stem cells (MSCs) isolated by fluorescence-activated cell sorting (FACS) from human adipose tissue...
February 2016: Tissue Engineering. Part A
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