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Matthew C Sapp, Varun K Krishnamurthy, Daniel S Puperi, Saheba Bhatnagar, Gabrielle Fatora, Neelesh Mutyala, K Jane Grande-Allen
Tissue oxygenation often plays a significant role in disease and is an essential design consideration for tissue engineering. Here, oxygen diffusion profiles of porcine aortic and mitral valve leaflets were determined using an oxygen diffusion chamber in conjunction with computational models. Results from these studies revealed the differences between aortic and mitral valve leaflet diffusion profiles and suggested that diffusion alone was insufficient for normal oxygen delivery in mitral valves. During fibrotic valve disease, leaflet thickening due to abnormal extracellular matrix is likely to reduce regional oxygen availability...
December 2016: Journal of the Royal Society, Interface
Carlos A Díaz-Balzac, Maisha Rahman, María I Lázaro-Peña, Lourdes A Martin Hernandez, Yehuda Salzberg, Cristina Aguirre-Chen, Zaven Kaprielian, Hannes E Bülow
Sensory dendrite arbors are patterned through cell-autonomously and non-cell-autonomously functioning factors [1-3]. Yet, only a few non-cell-autonomously acting proteins have been identified, including semaphorins [4, 5], brain-derived neurotrophic factors (BDNFs) [6], UNC-6/Netrin [7], and the conserved MNR-1/Menorin-SAX-7/L1CAM cell adhesion complex [8, 9]. This complex acts from the skin to pattern the stereotypic dendritic arbors of PVD and FLP somatosensory neurons in Caenorhabditis elegans through the leucine-rich transmembrane receptor DMA-1/LRR-TM expressed on PVD neurons [8, 9]...
September 12, 2016: Current Biology: CB
Andreas Kirschner, Melanie Thiede, Franziska Blaeschke, Günther H S Richter, Julia S Gerke, Michaela C Baldauf, Thomas G P Grünewald, Dirk H Busch, Stefan Burdach, Uwe Thiel
AIM: Autologous as well as allogeneic CD8+ T cells transduced with tumor antigen specific T cell receptors (TCR) may cause significant tumor lysis upon adoptive transfer. Besides unpredictable life-threatening off-target effects, these TCRs may unexpectedly commit fratricide. We hypothesized lysosome-associated membrane glycoprotein 1 (LAMP1, CD107a) to be a marker for fratricide in TCR transgenic CD8+ T cells. METHODS: We identified HLA-A*02:01/peptide-restricted T cells directed against ADRB3295...
August 30, 2016: Oncotarget
Xufang Zhang, Indira Prasadam, Wei Fang, Ross Crawford, Yin Xiao
OBJECTIVES: Hypoxia is known to stabilize hypoxia-inducible factor (HIF) and initiate angiogenic signalling cascade. However, cartilage living in hypoxia environment can maintain avascularity. It is well known that abrogation of avascularity is related to cartilage degradation in osteoarthritis (OA). The aims of present study were to investigate the role of Chondromodulin-1 (ChM-1), an endogenously anti-angiogenic protein in cartilage, during chondrocyte maturation and OA progression, as well as to explore the molecular mechanisms underlying the function of ChM-1 with a focus on HIF-2α pathway...
June 16, 2016: Osteoarthritis and Cartilage
Franziska Blaeschke, Uwe Thiel, Andreas Kirschner, Melanie Thiede, Rebeca Alba Rubio, David Schirmer, Thomas Kirchner, Günther H S Richter, Sabine Mall, Richard Klar, Stanley Riddell, Dirk H Busch, Angela Krackhardt, Thomas G P Grunewald, Stefan Burdach
The endochondral bone protein Chondromodulin-I (CHM1) provides oncogene addiction in Ewing sarcoma (ES). We pre-clinically tested the targetability of CHM1 by TCR transgenic, allo-restricted, peptide specific T cells to treat ES. We previously generated allo-restricted wildtype CD8+ T cells directed against the ES specific antigen CHM1319 causing specific responses against ES. However, utilization of these cells in current therapy protocols is hampered due to high complexity in production, relatively low cell numbers, and rapid T cell exhaustion...
July 12, 2016: Oncotarget
Zhuoyue Chen, Jing Wei, Jun Zhu, Wei Liu, Jihong Cui, Hongmin Li, Fulin Chen
BACKGROUND: Marrow mesenchymal stem cells (MSCs) can differentiate into specific phenotypes, including chondrocytes, and have been widely used for cartilage tissue engineering. However, cartilage grafts from MSCs exhibit phenotypic alternations after implantation, including matrix calcification and vascular ingrowth. METHODS: We compared chondromodulin-1 (Chm-1) expression between chondrocytes and MSCs. We found that chondrocytes expressed a high level of Chm-1...
May 5, 2016: Stem Cell Research & Therapy
Jie Shao, Linghong Gan, Jie Wang
Breast cancer affects one in every eight women, and has been associated with higher rates of female mortality than any other cancer type, with the exception of lung cancer. It has been reported that chondromodulin I (ChM-I) was able to suppress tumor angiogenesis and growth in vivo. In order to investigate the antitumor action of ChM‑I on human breast cancer cells, a plasmid expressing ChM‑I was constructed and transfected into human breast cancer cells using an adenoviral vector. Reverse transcription‑polymerase chain reaction detected ChM‑I expression in human breast cancer cell lines, whereas no expression was detected in the control groups...
May 2016: Molecular Medicine Reports
Jie Xu, Hengxing Cai, Qinggong Meng, Yingjie Li, Guoxin Chen, Wei Fang, Xing Long
BACKGROUND: A high density of blood vessels is observed in the perforated disks of temporomandibular joint (TMJ), but the underlying mechanism is unknown. This study aimed to explore the regulation of disk angiogenesis in the perforated disks. METHODS: Expressions of vascular endothelial growth factor (VEGF), angiogenin-1 (Ang-1), chondromodulin-1 (ChM-1), and thrombospondins-1 (TSP-1) were compared between healthy and perforated TMJ disk cells with or without interleukin-1β (IL-1β) incubation...
September 2016: Journal of Oral Pathology & Medicine
Pengfei Zhang, Ying Wang, Po Xu, Shiyuan Song, Xiaojuan Zhu, Zhenguo Shi, Shegan Gao, Xiaoshan Feng
Chondromodulin-1 (ChM1) is a cartilage-specific glycoprotein that stimulates the growth of chondrocytes and inhibits the tube formation of endothelial cells. Endogenously, ChM1 is expressed in the cartilage and is an anti-angiogenic factor. ChM1 has been reported to suppress the proliferation of multiple human tumor cells in an anchorage-independent manner. However, the role of ChM1 in carcinogenesis of gastric cancer remains unknown. By quantitative RT-PCR and western blotting we examined the expression of ChM1 in gastric cancer tissue and normal gastric tissue...
September 2015: International Journal of Oncology
Hidetaka Murata, Msataka Sunohara, Iwao Sato
Dentin matrix protein 1 (DMP-1) is an important factor in the mineralization of hard tissues. However, it has many other functions in addition to the regulation of mineralized tissues. We analyzed the expression and localization of DMP-1 by immunohistochemical staining and in situ hybridization in the developing mouse tongue during embryonic days 12.5 (E12.5), E14.5, E17.5, and E18.5. We also detected the mRNA abundance of tongue morphogenesis markers such as FGF6, TGF-β1, Collagen I, osteocalcin, chondromodulin 1, tenomodulin, Vascular endothelial growth factor (VEGF), caspase-3, and Aifm from embryonic stages by real-time RT-PCR...
July 2015: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Kayle Shapero, Jill Wylie-Sears, Robert A Levine, John E Mayer, Joyce Bischoff
Thickening of mitral leaflets, endothelial-to-mesenchymal transition (EndMT), and activated myofibroblast-like interstitial cells have been observed in ischemic mitral valve regurgitation. We set out to determine if interactions between mitral valve endothelial cells (VECs) and interstitial cells (VICs) might affect these alterations. We used in vitro co-culture in Transwell™ inserts to test the hypothesis that VICs secrete factors that inhibit EndMT and conversely, that VECs secrete factors that mitigate the activation of VICs to a myofibroblast-like, activated phenotype...
March 2015: Journal of Molecular and Cellular Cardiology
Shuang-Chun Xing, Yang Liu, Y Feng, Chen Jiang, Yu-Qiang Hu, Wei Sun, Xin-Hui Wang, Zhi-Yong Wei, Min Qi, Jing Liu, Li-Jie Zhai, Zhi-Qiang Wang
We have explored the role of Chondromodulin-I (ChM-I) in chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) in 3-dimensional (3D) scaffold for cartilage tissue engineering. BMSCs of Sprague Dawley (SD) rats were cultured on poly-(L-lactic acid) [PLLA] scaffolds with different pore sizes (80-200 μm, 200-450 μm) with or without surface modification by chitosan. Cell viability, proliferation, and morphology were measured using confocal microscope and the CCK-8 method. Untransfected BMSCs, BMSCs expressing pcDNA3...
March 2015: Cell Biology International
Yueqian Zhu, Yingying Zhang, Yu Liu, Ran Tao, Huitang Xia, Rui Zheng, Yuan Shi, Shengjian Tang, Wenjie Zhang, Wei Liu, Yilin Cao, Guangdong Zhou
Ectopic ossification of mesenchymal stem cell (MSC) regenerated cartilage has greatly restricted its application in repairing subcutaneous cartilage defects (such as nasal or auricular). Different from MSCs, chondrocytes can maintain stable chondrogenic phenotype in ectopic microenvironment, which was speculated to be related with the existence of antiangiogenic factors such as Chondromodulin-I (Chm-I). Therefore, the purpose of this study was to illustrate whether Chm-I was indispensable for stable ectopic chondrogenesis by chondrocyte, which may help to solve the problem of MSC ectopic ossification in the future...
February 2015: Tissue Engineering. Part A
Toshihiro Nagai, Masato Sato, Miyuki Kobayashi, Munetaka Yokoyama, Yoshiki Tani, Joji Mochida
INTRODUCTION: Angiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection. METHODS: First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligament transection, we used macroscopic and histological evaluations and real-time polymerase chain reaction (PCR) to examine the responses to intravenous (systemic) administration of bevacizumab (OAB IV group)...
2014: Arthritis Research & Therapy
E D'Asti, M Kool, S M Pfister, J Rak
BACKGROUND: The coagulation system becomes activated during progression and therapy of high-grade brain tumors. Triggering tissue factor (F3/TF) and thrombin receptors (F2R/PAR-1) may influence the vascular tumor microenvironment and angiogenesis irrespective of clinically apparent thrombosis. These processes are poorly understood in medulloblastoma (MB), in which diverse oncogenic pathways define at least four molecular disease subtypes (WNT, SHH, Group 3 and Group 4). We asked whether there is a link between molecular subtype and the network of vascular regulators expressed in MB...
November 2014: Journal of Thrombosis and Haemostasis: JTH
Shigenori Miura, Jun Kondo, Aki Takimoto, Hiroko Sano-Takai, Long Guo, Chisa Shukunami, Hideyuki Tanaka, Yuji Hiraki
Chondromodulin-I (ChM-I) is a 20-25 kDa anti-angiogenic glycoprotein in cartilage matrix. In the present study, we identified a novel 14-kDa species of ChM-I by immunoblotting, and purified it by immunoprecipitation with a newly raised monoclonal antibody against ChM-I. The N-terminal amino acid sequencing indicated that it was an N-terminal truncated form of ChM-I generated by the proteolytic cleavage at Asp37-Asp38. This 14-kDa ChM-I was shown by the modified Boyden chamber assay to have very little inhibitory activity on the VEGF-A-induced migration of vascular endothelial cells in contrast to the intact 20-25 kDa form of ChM-I (ID50 = 8 nM)...
2014: PloS One
Subhash C Juneja, Christian Veillette
This review summarizes the genetic alterations and knockdown approaches published in the literature to assess the role of key proteoglycans and glycoproteins in the structural development, function, and repair of tendon, ligament, and enthesis. The information was collected from (i) genetically altered mice, (ii) in vitro knockdown studies, (iii) genetic variants predisposition to injury, and (iv) human genetic diseases. The genes reviewed are for small leucine-rich proteoglycans (lumican, fibromodulin, biglycan, decorin, and asporin); dermatan sulfate epimerase (Dse) that alters structure of glycosaminoglycan and hence the function of small leucine-rich proteoglycans by converting glucuronic to iduronic acid; matricellular proteins (thrombospondin 2, secreted phosphoprotein 1 (Spp1), secreted protein acidic and rich in cysteine (Sparc), periostin, and tenascin X) including human tenascin C variants; and others, such as tenomodulin, leukocyte cell derived chemotaxin 1 (chondromodulin-I, ChM-I), CD44 antigen (Cd44), lubricin (Prg4), and aggrecan degrading gene, a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 5 (Adamts5)...
2013: Arthritis
Aki Takimoto, Hiromi Mohri, Chikara Kokubu, Yuji Hiraki, Chisa Shukunami
Paired box gene 1 (Pax1) indirectly promotes the early stages of chondrogenic differentiation through induction and transactivation of Nk3 homeobox 2 (Nkx3.2), a transcriptional repressor. Later in chondrogenic differentiation, Nkx3.2 blocks chondrocyte hypertrophy by repressing Runt-related transcription factor 2 (Runx2). Here we report the inhibitory action of Pax1 on chondrocyte maturation, independently of Nkx3.2. Upon cartilage formation, Pax1 expression in the ventral sclerotome was gradually decreased except for the perichondrial region of the vertebral bodies and the intervertebral region, both of which express SRY-box containing gene 9 (Sox9)...
December 10, 2013: Experimental Cell Research
Dai Kusumoto, Keiichi Fukuda
Recently, the aging of population and the changing dietary habit to western-style have led to increase in atherosclerotic diseases, such as myocardial infarction and cerebral infarction, in our country. Aortic valve diseases, whose mechanism is similar to atherosclerosis, are also increasing. The medication proved to be effective does not exist, and surgical management is major in treatment of these diseases. Although development of safer medication is expected, little is known about their molecular mechanism of the pathogenesis and the progression...
April 2013: Clinical Calcium
Masataka Fujii, Takayuki Furumatsu, Yusuke Yokoyama, Tomoko Kanazawa, Yuya Kajiki, Nobuhiro Abe, Toshifumi Ozaki
The meniscus is a fibrocartilaginous tissue that plays an important role in controlling complex biomechanics of the knee. A perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Anti-angiogenic molecules, such as chondromodulin-I (ChM-I) and endostatin, have pivotal roles in preserving the avascularity of cartilage. However, the anti-angiogenic role of ChM-I is unclear in the meniscus. We hypothesized that the inner meniscus might maintain its avascular feature by expressing ChM-I...
April 2013: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
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