Read by QxMD icon Read


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...
March 13, 2017: American Journal of Pathology
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: Non-healing 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, we examined the additive / synergistic effects of Hedgehog (Hh) and Nel-like protein-1 (NELL-1) on the osteogenic differentiation of mesenchymal stem cells in vitro. Here, we sought to leverage our previous findings by applying the combination of Smoothened agonist (SAG), Hh signal activator, and NELL-1 to an in vivo critical size bone defect model...
February 13, 2017: Plastic and Reconstructive Surgery
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...
2016: Journal of Visualized Experiments: JoVE
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
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
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
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
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
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
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
Mengmeng Liu, Qiang Wang, Ronghua Tang, Rongyu Cao, Xiaoying Wang
INTRODUCTION: Nel-like molecule-1 (Nell-1) with epidermal cell growth factor-like coding structures is a recently discovered secreted protein that can specifically induce osteoblast differentiation, bone formation, and bone regeneration. The expression and localization of Nell-1 during murine molar development suggest that this protein participates in odontoblastic differentiation. This study aims to assess the expression of Nell-1 in the pulp-dentin complex of human teeth and determine the effect of human recombinant Nell-1 (hrNell-1) on odontoblastic differentiation of cultured human dental pulp cells...
January 2016: Journal of Endodontics
Soonchul Lee, Xinli Zhang, Jia Shen, Aaron W James, Choon G Chung, Reef Hardy, Chenshuang Li, Caroline Girgius, Yulong Zhang, David Stoker, Huiming Wang, Benjamin M Wu, Bruno Peault, Kang Ting, Chia Soo
Autologous bone grafts (ABGs) are considered as the gold standard for spinal fusion. However, osteoporotic patients are poor candidates for ABGs due to limited osteogenic stem cell numbers and function of the bone microenvironment. There is a need for stem cell-based spinal fusion of proven efficacy under either osteoporotic or nonosteoporotic conditions. The purpose of this study is to determine the efficacy of human perivascular stem cells (hPSCs), a population of mesenchymal stem cells isolated from adipose tissue, in the presence and absence of NELL-1, an osteogenic protein, for spinal fusion in the osteoporosis...
October 2015: Stem Cells
Changlu Gao, Qian Zhang, Deyang Kong, Di Wu, Changlei Su, Jinxue Tong, Feng Chen, Qifan Zhang
Mass spectrometry (MS) enables rapid and sensitive qualitative and quantitative analyses of biomolecules (proteins, peptides, oligosaccharides, lipids, DNA, and RNA), drugs, and metabolites. MS has become an essential tool in modern biomedical research, including the analysis of DNA methylation. DNA methylation has been reported in many cancers, suggesting that it can be utilized as an early biomarker to improve the early diagnosis rate. Using matrix-assisted laser desorption/ionization time-of-flight MS and MassCLEAVE reagent, we compared Nell-1 hypermethylation levels among tumor tissues, paracarcinoma tissues, and normal tissues from gastric cancer patients...
2015: BioMed Research International
Aaron W James, Jia Shen, Xinli Zhang, Greg Asatrian, Raghav Goyal, Jin H Kwak, Lin Jiang, Benjamin Bengs, Cymbeline T Culiat, A Simon Turner, Howard B Seim Iii, Benjamin M Wu, Karen Lyons, John S Adams, Kang Ting, Chia Soo
NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption...
2015: Nature Communications
Jin Hee Kwak, Yulong Zhang, Juyoung Park, Eric Chen, Jia Shen, Chirag Chawan, Justine Tanjaya, Soonchul Lee, Xinli Zhang, Benjamin M Wu, Kang Ting, Chia Soo
Osteoporosis is a skeletal disorder attributable to an imbalance in osteoblast and osteoclast activity. NELL-1, a secretory protein that promotes osteogenesis while suppressing osteoclastic activity, holds potential as an osteoporosis therapy. Recently, we demonstrated that PEGylation of NELL-1 significantly improves its thermostability while preserving its bioactivity in vitro. However, the effect of PEGylation on the pharmacokinetics and osteogenic potential of NELL-1 in vivo have yet to be investigated...
July 2015: Biomaterials
Benjamin Smith, Todd Goldstein, Charles Ekstein
Normal bone healing is a complex process that eventually restores original structure and function to the site of trauma. However, clinical circumstances such as nonunion, critical-sized defects, systemic bone disease, and fusion procedures have stimulated a search for ways to enhance this normal healing process. Biologics are an important part of this search and many, including bone marrow aspirate concentrate, demineralized bone matrix, platelet-rich plasma, bone morphogenic proteins, and platelet-derived growth factor, are currently in clinical use...
June 2015: Current Reviews in Musculoskeletal Medicine
Jia Shen, Greg LaChaud, Kevork Khadarian, Swati Shrestha, Xinli Zhang, Chia Soo, Kang Ting, Sarah M Dry, Aaron W James
NELL-1 (NEL-like Protein 1) is an osteoinductive protein with increasing usage as a bone graft substitute in preclinical animal models. NELL-1 was first identified to have bone-forming properties by its overexpression in fusing cranial sutures. Since this time, addition of recombinant NELL-1 has been used to successfully induce bone formation in the calvarial, axial and appendicular skeleton. With increasing interest in the use of NELL-1 as a bone-graft substitute, we sought to examine the expression of NELL-1 in a wide spectrum of benign and malignant bone-forming skeletal tumors...
May 1, 2015: Biochemical and Biophysical Research Communications
Ritsuko Nakamura, Takeru Oyama, Ryosuke Tajiri, Atsushi Mizokami, Mikio Namiki, Masaru Nakamoto, Akishi Ooi
Neural epidermal growth factor-like like (NELL) 1 and 2 constitute a family of multimeric and multimodular extracellular glycoproteins. Although the osteogenic effects of NELL1 and functions of NELL2 in neural development have been reported, their expression and functions in cancer are largely unknown. In this study, we examined expression of NELL1 and NELL2 in renal cell carcinoma (RCC) using clinical specimens and cell lines. We show that, whereas NELL1 and NELL2 proteins are strongly expressed in renal tubules in non-cancerous areas of RCC specimens, their expression is significantly downregulated in cancerous areas...
May 2015: Cancer Science
Shen Pang, Jia Shen, Yi Liu, Feng Chen, Zhong Zheng, Aaron W James, Ching-Yun Hsu, Hong Zhang, Kevin S Lee, Chunling Wang, Chenshuang Li, Xuepeng Chen, Haichao Jia, Xinli Zhang, Chia Soo, Kang Ting
Neural epidermal growth factor-like (NEL)-like protein 1 (NELL-1) has been identified as an osteoinductive differentiation factor that promotes mesenchymal stem cell (MSC) osteogenic differentiation. In addition to full-length NELL-1, there are several NELL-1-related transcripts reported. We used rapid amplification of cDNA ends to recover potential cDNA of NELL-1 isoforms. A NELL-1 isoform with the N-terminal 240 amino acid (aa) residues truncated was identified. While full-length NELL-1 that contains 810 aa residues (NELL-1810 ) plays an important role in embryologic skeletal development, the N-terminal-truncated NELL-1 isoform (NELL-1570 ) was expressed postnatally...
March 2015: Stem Cells
Yulong Zhang, Omar Velasco, Xinli Zhang, Kang Ting, Chia Soo, Benjamin M Wu
Osteoporosis is a progressive bone disease due to low osteoblast activity and/or high osteoclast activity. NELL-1 is a potential therapy for osteoporosis because it specifically increases osteoblast differentiation. However, similar to other protein drugs, the bioavailability of NELL-1 may be limited by its in vivo half-life and rapid clearance from body. The purpose of the present study is to prolong NELL-1 circulation time in vivo by PEGylation with three monomeric PEG sizes (5, 20, 40 kDa). While linear PEG 5k yielded the most efficient PEGylation and the most thermally stable conjugate, linear PEG 20k resulted in the conjugate with the highest Mw and longest in vivo circulation...
August 2014: Biomaterials
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"