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https://www.readbyqxmd.com/read/28427181/metformin-inhibits-alk1-mediated-angiogenesis-via-activation-of-ampk
#1
Ying Ying, Takashi Ueta, Shanshan Jiang, Hui Lin, Yuanyuan Wang, Demetrios Vavvas, Rong Wen, Ye-Guang Chen, Zhijun Luo
Anti-VEGF therapy has been proven to be effective in the treatment of pathological angiogenesis. However, therapy resistance often occurs, leading to development of alternative approaches. The present study examines if AMPK negatively regulates ALK1-mediated signaling events and associated angiogenesis. Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415788/inhibitory-effects-of-bmp9-on-breast-cancer-cells-by-regulating-their-interaction-with-pre-adipocytes-adipocytes
#2
Ting Wang, Zhihui Zhang, Ke Wang, Jinshu Wang, Yayun Jiang, Jing Xia, Liyao Gou, Mengyao Liu, Lan Zhou, Tongchuan He, Yan Zhang
Bone morphogenetic protein 9 (BMP9) possesses multiple functions, but its effects on breast cancer cells in adipose microenvironment are still unclear. This study aimed to investigate whether BMP9 is able to modulate the interaction between pre-adipocytes/adipocytes and breast cancer cells. An in vitro co-culture system was established by using pre-adipocytes/adipocytes and MDA-MB-231 breast cancer cells with BMP9 over-expression. The leptin expression and leptin-induced signaling pathway were evaluated in this co-culture system...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406027/gelatin-derived-graphene-silicate-hybrid-materials-are-biocompatible-and-synergistically-promote-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells-mscs
#3
Yulong Zou, Nader Taheri Qazvini, Kylie Zane, Monirosadat Sanaz Sadati, Qiang Wei, Junyi Liao, Jiaming Fan, Dongzhe Song, Jianxiang Liu, Chao Ma, Xiangyang Qu, Liqun Chen, Xinyi Yu, Zhicai Zhang, Chen Zhao, Zongyue Zeng, Ruyi Zhang, Shujuan Yan, Tingting Wu, Xingye Wu, Yi Shu, Yasha Li, Wenwen Zhang, Russell R Reid, Michael J Lee, Jennifer M Wolf, Matthew Tirrell, Tong-Chuan He, Juan J de Pablo, Zhong-Liang Deng
Graphene-based materials have been used in many fields but have only found limited applications in biomedicine, including bone tissue engineering. Here we demonstrate that novel hybrid materials consisting of gelatin-derived graphene and silicate nanosheets of Laponite (GL) are biocompatible and promote osteogenic differentiation of mesenchymal stem cells (MSCs). Homogeneous cell attachment, long-term proliferation and osteogenic differentiation of MSCs on GL-scaffold were confirmed by optical microscopy, and scanning electron microscopy...
April 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28384643/notch-signaling-augments-bmp9-induced-bone-formation-by-promoting-the-osteogenesis-angiogenesis-coupling-process-in-mesenchymal-stem-cells-mscs
#4
Junyi Liao, Qiang Wei, Yulong Zou, Jiaming Fan, Dongzhe Song, Jing Cui, Wenwen Zhang, Yunxiao Zhu, Chao Ma, Xue Hu, Xiangyang Qu, Liqun Chen, Xinyi Yu, Zhicai Zhang, Claire Wang, Chen Zhao, Zongyue Zeng, Ruyi Zhang, Shujuan Yan, Tingting Wu, Xingye Wu, Yi Shu, Jiayan Lei, Yasha Li, Hue H Luu, Michael J Lee, Russell R Reid, Guillermo A Ameer, Jennifer Moriatis Wolf, Tong-Chuan He, Wei Huang
BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into several lineages including bone. Successful bone formation requires osteogenesis and angiogenesis coupling of MSCs. Here, we investigate if simultaneous activation of BMP9 and Notch signaling yields effective osteogenesis-angiogenesis coupling in MSCs. METHODS: Recently-characterized immortalized mouse adipose-derived progenitors (iMADs) were used as MSC source...
April 4, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28365680/pro-inflammatory-cytokine-tnf-%C3%AE-attenuates-bmp9-induced-osteo-odontoblastic-differentiation-of-the-stem-cells-of-dental-apical-papilla-scaps
#5
Feilong Wang, Ying Jiang, Xia Huang, Qiao Liu, Yan Zhang, Wenping Luo, Fugui Zhang, Pengfei Zhou, Juhong Lin, Hongmei Zhang
BACKGROUND/AIMS: Periapical periodontitis is a common oral disease caused by bacterial invasion of the tooth pulp, which usually leads to local release of pro-inflammatory cytokines and osteolytic lesion. This study is intended to examine the effect of TNF-α on BMP9-induced osteogenic differentiation of the stem cells of dental apical papilla (SCAPs). METHODS: Rat model of periapical periodontitis was established. TNF-α expression was assessed. Osteogenic markers and ectopic bone formation in iSCAPs were analyzed upon BMP9 and TNF-α treatment...
March 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28350136/all-trans-retinoic-acid-restored-the-osteogenic-ability-of-bmp9-in-osteosarcoma-through-the-p38-mapk-pathway
#6
Nian Wu, Ruidong Li, Zijun Meng, Mao Nie, Qianzhao Chen, Baicheng He, Zhongliang Deng, Liangjun Yin
Osteosarcoma (OS) is the most common malignant bone tumour and is considered to be a disease caused by a dysfunction in differentiation. Bone morphogenetic protein 9 (BMP9) is the most potent osteogenic factor in mesenchymal stem cells, but it cannot induce osteogenic differentiation in OS cells; this might be one of the determinants in the pathogenesis of OS. All-trans retinoic acid (ATRA) can induce osteogenic differentiation of OS cells and potentiate BMP9-induced osteogenesis in preadipocytes. However, the concomitant effect of ATRA and BMP9 in OS cells is unclear; therefore, in the present study, we focused on this topic...
March 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28298363/mutual-interaction-between-endothelial-cells-and-mural-cells-enhances-bmp9-signaling-in-endothelial-cells
#7
Yuki Tachida, Nanae Izumi, Toyo Sakurai, Hideki Kobayashi
Hereditary hemorrhagic telangiectasia is characterized by the formation of abnormal vascular networks and caused by the mutation of genes involved in BMP9 signaling. It is also known that the interaction between endothelial cells (ECs) and mural cells (MCs) is critical to maintain vessel integrity. However, it has not yet fully been uncovered whether the EC-MC interaction affects BMP9 signaling or not. To elucidate this point, we analyzed BMP9 signaling in a co-culture of several types of human primary culture ECs and MCs...
March 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28249039/repair-of-critical-sized-cranial-defects-with-bmp9-transduced-calvarial-cells-delivered-in-a-thermoresponsive-scaffold
#8
Zari P Dumanian, Viktor Tollemar, Jixing Ye, Minpeng Lu, Yunxiao Zhu, Junyi Liao, Guillermo A Ameer, Tong-Chuan He, Russell R Reid
Large skeletal defects caused by trauma, congenital malformations, and post-oncologic resections of the calvarium present major challenges to the reconstructive surgeon. We previously identified BMP-9 as the most osteogenic BMP in vitro and in vivo. Here we sought to investigate the bone regenerative capacity of murine-derived calvarial mesenchymal progenitor cells (iCALs) transduced by BMP-9 in the context of healing critical-sized calvarial defects. To accomplish this, the transduced cells were delivered to the defect site within a thermoresponsive biodegradable scaffold consisting of poly(polyethylene glycol citrate-co-N-isopropylacrylamide mixed with gelatin (PPCN-g)...
2017: PloS One
https://www.readbyqxmd.com/read/28228716/intranasal-bmp9-ameliorates-alzheimer-disease-like-pathology-and-cognitive-deficits-in-app-ps1-transgenic-mice
#9
Zigao Wang, Lu Xiong, Wenbin Wan, Lijie Duan, Xiaojing Bai, Hengbing Zu
Alzheimer's disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28214873/nel-like-molecule-1-nell1-is-regulated-by-bone-morphogenetic-protein-9-bmp9-and-potentiates-bmp9-induced-osteogenic-differentiation-at-the-expense-of-adipogenesis-in-mesenchymal-stem-cells
#10
Jing Wang, Junyi Liao, Fugui Zhang, Dongzhe Song, Minpeng Lu, Jianxiang Liu, Qiang Wei, Shengli Tang, Hao Liu, Jiaming Fan, Yulong Zou, Dan Guo, Jiayi Huang, Feng Liu, Chao Ma, Xue Hu, Li Li, Xiangyang Qu, Liqun Chen, Yaguang Weng, Michael J Lee, Tong-Chuan He, Russell R Reid, Jiye Zhang
BACKGROUND: BMP9 induces both osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs). Nell1 is a secretory glycoprotein with osteoinductive and anti-adipogenic activities. We investigated the role of Nell1 in BMP9-induced osteogenesis and adipogenesis in MSCs. METHODS: Previously characterized MSCs iMEFs were used. Overexpression of BMP9 and NELL1 or silencing of mouse Nell1 was mediated by adenoviral vectors. Early and late osteogenic and adipogenic markers were assessed by staining techniques and qPCR analysis...
January 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#11
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
February 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28125843/pituitary-adenylate-cyclase-activating-peptide-pacap-a-novel-secretagogue-regulates-secreted-morphogens-in-newborn-rat-retina
#12
Monika Lakk, Viktoria Denes, Karmen Kovacs, Orsolya Hideg, Bence F Szabo, Robert Gabriel
Purpose: Pituitary adenylate cyclase-activating peptide (PACAP)1-38 has been reported to be responsible for regulation of a disparate array of developmental processes in the central nervous system, and its antiapoptotic effect has been revealed in numerous models, pointing to its relevance in the etiology of neurodegenerative disorders. However, its function in retinal development remains unclear. Here, we aimed to point out that versatility can be achieved through interaction with other regulators, in which PACAP can act indirectly on the retinal microenvironment...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28103025/identification-of-the-first-selective-activin-receptor-like-kinase-1-inhibitor-a-reversible-version-of-l-783277
#13
Hanna Cho, Sandip Sengupta, Sean S H Jeon, Wooyoung Hur, Hwan Geun Choi, Hong-Seog Seo, Byung Joo Lee, Jeong Hun Kim, Minhwan Chung, Noo Li Jeon, Nam Doo Kim, Taebo Sim
We synthesized 1 (San78-130), a reversible version of L-783277, as a selective and potent ALK1 inhibitor. Our study showed that 1 possesses great kinase selectivity against a panel of 342 kinases and more potent activity against ALK1 than L-783277. Among the six ALK isotypes (ALK1-6), ALK1 is most significantly inhibited by compound 1. Compound 1 suppresses the BMP9-induced Smad1/5 pathway by mainly inhibiting ALK1 in C2C12 cells. Our molecular dynamics simulations suggest that H-bonding interaction between the C-4' hydroxyl group of 1 and Arg334 of ALK1 substantially contributes to the ALK1 inhibition...
February 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28052093/bone-morphogenetic-protein-9-enhances-osteogenic-differentiation-of-human-periodontal-ligament-stem-cells-via-the-jnk-pathway
#14
Pei Wang, Yanen Wang, Weizhong Tang, Xingxing Wang, Yanan Pang, Su Yang, Yibo Wei, Haochen Gao, Dalin Wang, Zhizhong Cao
Bone morphogenetic protein-9 (BMP9) shows great osteoinductive potential in bone regeneration. Periodontal ligament stem cells (PDLSCs) with multi-differentiation capability and low immunogenicity are increasingly used as seed cells for periodontal regenerative therapies. In the present study, we investigated the potent osteogenic activity of BMP9 on human PDLSCs (hPDLSCs), in which the c-Jun N-terminal kinase (JNK) pathway is possibly involved. Our results showed that JNK inhibition by the specific inhibitor SP600125 or adenovirus expressing small interfering RNA (siRNA) targeting JNK (AdR-si-JNK) significantly decreased BMP9-induced gene and protein expression of early and late osteogenic markers, such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN), in hPDLSCs...
2017: PloS One
https://www.readbyqxmd.com/read/27996168/follicle-stimulating-hormone-%C3%AE-subunit-potentiates-bone-morphogenetic-protein-9-induced-osteogenic-differentiation-in-mouse-embryonic-fibroblasts
#15
Xiao-Ya Su, Xiang Zou, Qian-Zhao Chen, Yu-Hua Zeng, Ying Shao, Bai-Cheng He, Hong Liu
Postmenopausal osteoporosis (PMOP)-related fractures usually result in morbidity and mortality in aging women, so it remains a global public health concern, and new effective safe treatments are urgently needed recently. Efficient osteogenesis from mesenchymal stem cells (MSCs) would have the clinical application potential in treating multiple osteal disorders. Follicle-stimulating hormone (FSH), a pituitary glycoprotein hormone highly associated with menopausal bone turnover, whose peculiar part of receptor binding is follicle-stimulating hormone β-subunit (FSHβ)...
December 20, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27897192/pi3-kinase-inhibition-improves-vascular-malformations-in-mouse-models-of-hereditary-haemorrhagic-telangiectasia
#16
Roxana Ola, Alexandre Dubrac, Jinah Han, Feng Zhang, Jennifer S Fang, Bruno Larrivée, Monica Lee, Ana A Urarte, Jan R Kraehling, Gael Genet, Karen K Hirschi, William C Sessa, Francesc V Canals, Mariona Graupera, Minhong Yan, Lawrence H Young, Paul S Oh, Anne Eichmann
Activin receptor-like kinase 1 (ALK1) is an endothelial serine-threonine kinase receptor for bone morphogenetic proteins (BMPs) 9 and 10. Inactivating mutations in the ALK1 gene cause hereditary haemorrhagic telangiectasia type 2 (HHT2), a disabling disease characterized by excessive angiogenesis with arteriovenous malformations (AVMs). Here we show that inducible, endothelial-specific homozygous Alk1 inactivation and BMP9/10 ligand blockade both lead to AVM formation in postnatal retinal vessels and internal organs including the gastrointestinal (GI) tract in mice...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27875556/mxa-is-a-novel-regulator-of-endosome-associated-transcriptional-signaling-by-bone-morphogenetic-proteins-4-and-9-bmp4-and-bmp9
#17
Huijuan Yuan, Pravin B Sehgal
There is confusion about the role that IFN-α plays in the pathogenesis of pulmonary arterial hypertension (PAH) with different investigators reporting a causative or a protective role. There is now clear evidence in PAH pathogenesis for the involvement of BMP4 and BMP9 signaling, and its disruption by mutations in BMPR2. In the present study, we investigated MxA, an IFN-α-inducible cytoplasmic dynamin-family GTPase for effects on BMP4/9 signaling, including in the presence of PAH-disease-associated mutants of BMPR2...
2016: PloS One
https://www.readbyqxmd.com/read/27874028/a-mouse-model-of-hereditary-hemorrhagic-telangiectasia-generated-by-transmammary-delivered-immunoblocking-of-bmp9-and-bmp10
#18
Santiago Ruiz, Haitian Zhao, Pallavi Chandakkar, Prodyot K Chatterjee, Julien Papoin, Lionel Blanc, Christine N Metz, Fabien Campagne, Philippe Marambaud
Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening genetic vascular disorder caused by loss-of-function mutations in the genes encoding activin receptor-like kinase 1 (ALK1), endoglin, Smad4, and bone morphogenetic protein 9 (BMP9). Injections of mouse neonates with BMP9/10 blocking antibodies lead to HHT-like vascular defects in the postnatal retinal angiogenesis model. Mothers and their newborns share the same immunity through the transfer of maternal antibodies during lactation...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27859405/effects-of-bmp9-and-pulsed-electromagnetic-fields-on-the-proliferation-and-osteogenic-differentiation-of-human-periodontal-ligament-stem-cells
#19
Tingting Wang, Pei Wang, Zhizhong Cao, Xingxing Wang, Dalin Wang, Yaxian Shen, Da Jing, Erping Luo, Weizhong Tang
Periodontal ligament stem cells (PDLSCs) have been confirmed to have self-renewal capacity and multidifferentiation potential and are good candidates for periodontal tissue regeneration. Pulsed electromagnetic field (PEMF) has been demonstrated to promote osteogenesis in non-union fractures, partly by regulating mesenchymal stem cells or osteoblast activity. However, there is no report about the osteo-inductive effect of PEMF stimulation on human PDLSCs (hPDLSCs). Thus, we tested the hypothesis that PEMF biophysical stimulation alone has an influence on the proliferation and osteogenic differentiation of hPDLSCs...
January 2017: Bioelectromagnetics
https://www.readbyqxmd.com/read/27741515/compound-genetically-engineered-mouse-models-of-cancer-reveal-dual-targeting-of-alk1-and-endoglin-as-a-synergistic-opportunity-to-impinge-on-angiogenic-tgf-%C3%AE-signaling
#20
Nikolas M Eleftheriou, Jonas Sjölund, Matteo Bocci, Eliane Cortez, Se-Jin Lee, Sara I Cunha, Kristian Pietras
Angiogenesis occurs early in tumor development, sustains primary tumor growth and provides a route for metastatic escape. The TGF-β family receptors modulate angiogenesis via endothelial-cell specific pathways. Here we investigate the interaction of two such receptors, ALK1 and endoglin, in pancreatic neuroendocrine tumors (PanNET). Independently, ALK1 and endoglin deficiencies exhibited genetically divergent phenotypes, while both highly correlate to an endothelial metagene in human and mouse PanNETs. A concurrent deficiency of both receptors synergistically decreased tumor burden to a greater extent than either individual knockdown...
December 20, 2016: Oncotarget
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