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Hai Li, Dahang Zhao, Shengjing Wang, Jing Ding, Li Zhao
It has been confirmed that bone morphogenetic protein-9 (BMP-9) promotes the differentiation of osteoblasts. However, the ways in which BMP‑9 exerts its effects on the differentiation of osteoclasts and bone resorption remain to be elucidated. The present study was designed to investigate the roles and the molecular mechanism of BMP‑9 on the proliferation and differentiation of osteoclast precursors in vitro. Mouse spleen macrophages (RAW 264.7 cells) were cultured in the presence of receptor activator for nuclear factor‑κb ligand (RANKL) in vitro...
October 5, 2016: Molecular Medicine Reports
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No abstract text is available yet for this article.
October 15, 2016: Cancer Research
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...
October 12, 2016: Oncotarget
Candela R González, Mariano Ar Amer, Alfredo D Vitullo, Silvia I González-Calvar, María I Vacas
Saliva is the first barrier to entry of bacteria and viruses into the body. The submandibular glands (SMG) contribute to the maintenance of oral health and regulation of immune/ inflam matory responses. Previous studies suggest that transforming growth factor beta 1 (TGFB1) may contribute to salivary gland fibrosis but the expression of the TGFB1 system in the SMG has not been elucidated. Thus, the aim of this study was to analyze in rat SMG the immunolocalization of TGFB1 and its specific receptors ALK5 (profibrotic) and ALK1 (proproliferative) and the coreceptor endoglin (EDG) in a bilateral experimental periodontitis (EP) model (cotton thread ligature around the neck of the first lower molars) for 1 and 6 weeks...
September 2016: Acta Odontológica Latinoamericana: AOL
S Shanmugaapriya, A van Caam, L de Kroon, Elly L Vitters, B Walgreen, H van Beuningen, E Blaney Davidson, Peter M van der Kraan
OBJECTIVE: RNA-binding protein with multiple splicing (RBPMS) has been shown to physically interact with Smads and enhance transforming growth factor-β (TGF-β)-mediated Smad2/3 transcriptional activity in mammalian cells. Objective of this study was to examine whether expression of RBPMS is regulated by interleukin-1β (IL)-1β and TGF-β superfamily growth factors and whether expression of RBPMS is altered during aging and experimental osteoarthritis. METHODS: Expression of RBPMS protein was investigated in chondrocyte cell lines of murine (H4) and human (G6) origin using Western blot analysis...
October 2016: Cartilage
Hany Sakr, Michael Cruise, Prabhleen Chahal, Claudiu Cotta, James Cook, Sricharan Chalikonda, Steven Rosenblatt, Fatima Hamadeh, Omar Al-Nourhji, Charles D Sturgis
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare distinct type of non-Hodgkin's lymphoma that arises in association with alterations of the ALK gene. This distinct disease entity is typically associated with an aggressive clinical course and appears in light microscopic preparations as a monomorphic population of large, immunoblast-like cells. In this report, we describe a case of ALK+ LBCL diagnosed by transgastric endoscopic ultrasound-guided fine needle aspiration (EUS FNA) of splenic hilar lymph nodes...
September 30, 2016: Diagnostic Cytopathology
Claudio A Franco, Holger Gerhardt
Bone morphogenic proteins (BMPs) and blood flow regulate vascular remodeling and homeostasis. In this issue, Baeyens et al. (2016. J. Cell Biol show that blood flow sensitizes endothelial cells to BMP9 signaling by triggering Alk1/ENG complexing to suppress cell proliferation and to recruit mural cells, thereby establishing endothelial quiescence.
September 26, 2016: Journal of Cell Biology
Antonio Jimeno, Marshall R Posner, Lori J Wirth, Nabil F Saba, Roger B Cohen, Elizabeth C Popa, Athanassios Argiris, Kenneth F Grossmann, Ammar Sukari, Dawn Wilson, Xiaosha Zhang, Jade Sun, Chad Glasser, Kenneth M Attie, Matthew L Sherman, Susan S Pandya, Jared Weiss
BACKGROUND: Patients with platinum-refractory, recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) have limited options. Activin receptor-like kinase 1 (ALK1) is a type I receptor of the transforming growth factor β superfamily expressed on activated endothelial cells. Dalantercept is an ALK1 receptor fusion protein that acts as a ligand trap to block signaling through ALK1 and inhibits stages of angiogenesis involved in blood vessel maturation and stabilization...
September 20, 2016: Cancer
Nicolas Baeyens, Bruno Larrivée, Roxana Ola, Brielle Hayward-Piatkowskyi, Alexandre Dubrac, Billy Huang, Tyler D Ross, Brian G Coon, Elizabeth Min, Maya Tsarfati, Haibin Tong, Anne Eichmann, Martin A Schwartz
Morphogenesis of the vascular system is strongly modulated by mechanical forces from blood flow. Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal-dominant disease in which arteriovenous malformations and telangiectasias accumulate with age. Most cases are linked to heterozygous mutations in Alk1 or Endoglin, receptors for bone morphogenetic proteins (BMPs) 9 and 10. Evidence suggests that a second hit results in clonal expansion of endothelial cells to form lesions with poor mural cell coverage that spontaneously rupture and bleed...
September 26, 2016: Journal of Cell Biology
Ayako Chida, Masaki Shintani, Hajime Wakamatsu, Yoshiyuki Tsutsumi, Yuo Iizuka, Nanako Kawaguchi, Yoshiyuki Furutani, Kei Inai, Shigeaki Nonoyama, Toshio Nakanishi
Although mutations in the RASA1 gene in vein of Galen aneurysmal malformation (VGAM) and an endoglin gene mutation in a VGAM patient with a family history of hereditary hemorrhagic telangiectasia (HHT) have been identified, most VGAM cases have no mutation in these genes. We sought to detect mutations in other genes related to HHT. We screened for mutations in RASA1 and three genes (endoglin, activin receptor-like kinase 1 (ACVRL1), encoding ALK1, and SMAD4) related to HHT in four VGAM patients. One variant (c...
December 2013: Journal of Pediatric Genetics
Meihua Jin, Juyoung Lee, Kyung-Yup Lee, Zhengyong Jin, Jhang Ho Pak, Han-Suk Kim
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a main chronic lung disease commonly occurs in preterm infants. BPD is characterized by impaired alveolarization and vascularization of the developing lung. Transforming growth factor-β (TGF-β) signaling pathway is known to play an important role during lung vascular development. In the present study, we examined whether the regulation of TGF-β-ALK-Smad signaling pathway influence on the disruption of pulmonary vascular development in newborn rats as hyperoxia-induced BPD model...
September 12, 2016: Experimental Lung Research
Jie Song, Christina A Eichstaedt, Rebecca Rodríguez Viales, Nicola Benjamin, Satenik Harutyunova, Christine Fischer, Ekkehard Grünig, Katrin Hinderhofer
In the present study we developed a new specific gene panel for pulmonary arterial hypertension (PAH) including major disease genes and further candidates. We assessed 37 patients with invasively confirmed PAH and five relatives of affected patients for genetic testing. A new PAH-specific gene panel was designed using next generation sequencing (NGS) including 12 known disease genes and 17 further candidates. Any potential pathogenic variants were reassessed by Sanger sequencing. Twenty-two of the 37 patients (59%) had a mutation in BMPR2, ALK1, ENG or EIF2AK4 genes identified by panel and Sanger sequencing...
November 1, 2016: Clinical Science (1979-)
Amaya García de Vinuesa, Matteo Bocci, Kristian Pietras, Peter Ten Dijke
Angiogenesis is a hallmark of cancer and is now a validated therapeutic target in the clinical setting. Despite the initial success, anti-angiogenic compounds impinging on the vascular endothelial growth factor (VEGF) pathway display limited survival benefits in patients and resistance often develops due to activation of alternative pathways. Thus, finding and validating new targets is highly warranted. Activin receptor-like kinase (ALK)1 is a transforming growth factor beta (TGF-β) type I receptor predominantly expressed in actively proliferating endothelial cells (ECs)...
August 15, 2016: Biochemical Society Transactions
Wei Li, Richard M Salmon, He Jiang, Nicholas W Morrell
Bone morphogenetic protein (BMP)9 and BMP10 are high affinity ligands for activin receptor-like kinase 1 (ALK1), a type I BMP receptor mainly expressed on vascular endothelial cells (ECs). ALK1-mediated BMP9/BMP10 signalling pathways have emerged as essential in EC biology and in angiogenesis. Several genetic mutations in the genes encoding the ligands and receptors of this pathway have been reported in two cardiovascular diseases, pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT)...
August 15, 2016: Biochemical Society Transactions
Kalonji Ntumba, Naoufal Akla, S Paul Oh, Anne Eichmann, Bruno Larrivée
Age-related macular degeneration (AMD) is the leading cause of blindness in aging populations of industrialized countries. The drawbacks of inhibitors of vascular endothelial growth factor (VEGFs) currently used for the treatment of AMD, which include resistance and potential serious side-effects, require the identification of new therapeutic targets to modulate angiogenesis. BMP9 signaling through the endothelial Alk1 serine-threonine kinase receptor modulates the response of endothelial cells to VEGF and promotes vessel quiescence and maturation during development...
August 10, 2016: Oncotarget
Ghizlene Lahlou, Marion Classe, Michel Wassef, Pierre-Alexandre Just, Nicolas Le Clerc, Philippe Herman, Benjamin Verillaud
Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal tumors initially described in the lung. About half of them exhibit expression of the ALK1 protein, generally resulting from a gene rearrangement. Paranasal sinus IMTs are extremely uncommon, and gene rearrangement of ALK1 is very rare in this localization. A 47-year-old woman presented with rapidly progressive vision loss in her left eye. Clinical and imaging work-up revealed a tumor invading the left ethmoidal and sphenoidal sinuses and extending into the nasal cavity, the orbit and the skull base...
July 21, 2016: Head and Neck Pathology
Li Ma, Fanxia Shen, Kristine Jun, Chen Bao, Robert Kuo, William L Young, Stephen L Nishimura, Hua Su
Brain arteriovenous malformation (bAVM), characterized by tangled dysplastic vessels, is an important cause of intracranial hemorrhage in young adults, and its pathogenesis and progression are not fully understood. Patients with haploinsufficiency of transforming growth factor-β (TGF-β) receptors, activin receptor-like kinase 1 (ALK1) or endoglin (ENG) have a higher incidence of bAVM than the general population. However, bAVM does not develop effectively in mice with the same haploinsufficiency. The expression of integrin β8 subunit (ITGB8), another member in the TGF-β superfamily, is reduced in sporadic human bAVM...
June 29, 2016: Translational Stroke Research
Jin Sung Jang, Xiaoke Wang, Peter T Vedell, Ji Wen, Jinghui Zhang, David W Ellison, Jared M Evans, Sarah H Johnson, Ping Yang, William R Sukov, Andre Oliveira, George Vasmatzis, Zhifu Sun, Jin Jen, Eunhee S Yi
BACKGROUND: We performed a genomic study in lung adenocarcinoma cases with discordant anaplastic lymphoma kinase (ALK) status by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC). METHODS: DNA from formalin-fixed paraffin embedded (FFPE) tissues of 16 discordant (4 FISH+/IHC- and 12 FISH-/IHC+) cases by Vysis ALK Break Apart FISH and ALK1 IHC testing were subjected to whole gene capture and next generation sequencing (NGS) of nine genes including ALK, EML4, KIF5B, SND1, BRAF, RET, EZR, ROS1, and TERT...
June 22, 2016: Journal of Thoracic Oncology
Rui Zhang, Zhenying Han, Vincent Degos, Fanxia Shen, Eun-Jung Choi, Zhengda Sun, Shuai Kang, Michael Wong, Wan Zhu, Lei Zhan, Helen M Arthur, S Paul Oh, Marie E Faughnan, Hua Su
An abnormally high number of macrophages are present in human brain arteriovenous malformations (bAVM) with or without evidence of prior hemorrhage, causing unresolved inflammation that may enhance abnormal vascular remodeling and exacerbate the bAVM phenotype. The reasons for macrophage accumulation at the bAVM sites are not known. We tested the hypothesis that persistent infiltration and pro-inflammatory differentiation of monocytes in angiogenic tissues increase the macrophage burden in bAVM using two mouse models and human monocytes...
October 2016: Angiogenesis
Elizabeth R Rochon, Prahlad G Menon, Beth L Roman
Heterozygous loss of the arterial-specific TGFβ type I receptor, activin receptor-like kinase 1 (ALK1; ACVRL1), causes hereditary hemorrhagic telangiectasia (HHT). HHT is characterized by development of fragile, direct connections between arteries and veins, or arteriovenous malformations (AVMs). However, how decreased ALK1 signaling leads to AVMs is unknown. To understand the cellular mis-steps that cause AVMs, we assessed endothelial cell behavior in alk1-deficient zebrafish embryos, which develop cranial AVMs...
July 15, 2016: Development
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