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Amel Dudakovic, Emily T Camilleri, Scott M Riester, Christopher R Paradise, Martina Gluscevic, Thomas M O'Toole, Roman Thaler, Jared M Evans, Huihuang Yan, Malayannan Subramaniam, John R Hawse, Gary S Stein, Martin A Montecino, Meghan E McGee-Lawrence, Jennifer J Westendorf, Andre J van Wijnen
Perturbations in skeletal development and bone degeneration may result in reduced bone mass and quality leading to greater fracture risk. Bone loss is mitigated by bone protective therapies, but there is a clinical need for new bone-anabolic agents. Previous work has demonstrated that enhancer of zeste homolog 2 (Ezh2), a histone 3 lysine 27 (H3K27) methyltransferase, suppressed differentiation of osteogenic progenitors. Here, we investigated if inhibition of Ezh2 can be leveraged for bone stimulatory applications...
October 10, 2016: Journal of Biological Chemistry
Flora Clément, Xinyi Xu, Caterina F Donini, Alice Clément, Soleilmane Omarjee, Emmanuel Delay, Isabelle Treilleux, Béatrice Fervers, Muriel Le Romancer, Pascale A Cohen, Véronique Maguer-Satta
Bone morphogenetic protein 2 (BMP2) and BMP4 are key regulators of the fate and differentiation of human mammary epithelial stem cells (SCs), as well as of their niches, and are involved in breast cancer development. We established that MCF10A immature mammary epithelial cells reliably reproduce the BMP response that we previously identified in human primary epithelial SCs. In this model, we observed that BMP2 promotes luminal progenitor commitment and expansion, whereas BMP4 prevents lineage differentiation...
October 14, 2016: Cell Death and Differentiation
Karen Beets, Michael W Staring, Nathan Criem, Elke Maas, Niels Schellinx, Susana M Chuva de Sousa Lopes, Lieve Umans, An Zwijsen
BACKGROUND: Bone morphogenetic protein (BMP) signalling has emerged as a fundamental pathway in endothelial cell biology and deregulation of this pathway is implicated in several vascular disorders. BMP signalling output in endothelial cells is highly context- and dose-dependent. Phosphorylation of the BMP intracellular effectors, SMAD1/5/9, is routinely used to monitor BMP signalling activity. To better understand the in vivo context-dependency of BMP-SMAD signalling, we investigated differences in BMP-SMAD transcriptional activity in different vascular beds during mouse embryonic and postnatal stages...
October 10, 2016: BMC Developmental Biology
June Baik, Alessandro Magli, Naoyuki Tahara, Scott A Swanson, Naoko Koyano-Nakagawa, Luciene Borges, Ron Stewart, Daniel J Garry, Yasuhiko Kawakami, James A Thomson, Rita C R Perlingeiro
Mechanisms of haematopoietic and cardiac patterning remain poorly understood. Here we show that the BMP and Wnt signalling pathways are integrated in an endoglin (Eng)-dependent manner in cardiac and haematopoietic lineage specification. Eng is expressed in early mesoderm and marks both haematopoietic and cardiac progenitors. In the absence of Eng, yolk sacs inappropriately express the cardiac marker, Nkx2.5. Conversely, high levels of Eng in vitro and in vivo increase haematopoiesis and inhibit cardiogenesis...
October 7, 2016: Nature Communications
Q Schick Auh, Kyung Ran Park, Hyung Mun Yun, Hyun Chang Lim, Ga Hyun Kim, Dong Sung Lee, Youn Chul Kim, Hyuncheol Oh, Eun Cheol Kim
Although sulfuretin, the major flavonoid of Rhus verniciflua Stokes, has a variety of biological actions, its in vitro and in vivo effects on osteogenic potential remain poorly understood. The objective of the present study was to investigate the effects of sulfuretin on in vitro osteoblastic differentiation and the underlying signal pathway mechanisms in primary cultured osteoblasts and on in vivo bone formation using critical-sized calvarial defects in mice. Sulfuretin promoted osteogenic differentiation of primary osteoblasts, with increased ALP activity and mineralization, and upregulated differentiation markers, including ALP, osteocalcin, and osteopontin, in a concentration-dependent manner...
October 4, 2016: Oncotarget
Roy Baas, Ayestha Sijm, Hetty A A M van Teeffelen, Robert van Es, Harmjan R Vos, H Th Marc Timmers
Gene-specific transcription factors (GSTFs) control gene transcription by DNA binding and specific protein complex recruitment, which regulates promoter accessibility for transcription initiation by RNA polymerase II. Mutations in the GSTFs Suppressor of Mothers Against Decapentaplegic 2 (SMAD2) and SMAD4 are frequently associated with colon and rectal carcinomas. These proteins play an important role in bone morphogenic protein (BMP) and transforming growth factor β (TGF-β) signaling pathways controlling cell fate and proliferation...
October 4, 2016: Journal of Biological Chemistry
Pouria HosseinNia, Mehdi Hajian, Mojtaba Tahmoorespur, Sayyed Morteza Hosseini, Somayyeh Ostadhosseini, Mohammad Reza Nasiri, Mohammad Hossein Nasr-Esfahani
BACKGROUND: Little is understood about the regulation of gene expression during early goat embryo development. This study investigated the expression profile of 19 genes, known to be critical for early embryo development in mouse and human, at five different stages of goat in vitro embryo development (oocyte, 8-16 cell, morula, day-7 blastocyst, and day 14 blastocyst). MATERIALS AND METHODS: In this experimental study, stage-specific profiling using real time-quantitative polymerase chain reaction (RT-qPCR) revealed robust and dynamic patterns of stage-specific gene activity that fall into four major clusters depending on their respective mRNA profiles...
October 2016: International Journal of Fertility & Sterility
Wu Yan, Haoxiang Zhang, Jingwen Li, Caifei Shen, Yiju Xia, Pu Wang, Yafei Zhang, Ji Feng, Shunzi Shao, Xiaona Yu, Dianchun Fang
INTRODUCTION: Barrett's esophagus is a metaplastic lesion. However, the cellular and molecular mechanisms involved are poorly understood. The aim of this study was to investigate the roles of KLF4 and BMP4 in the pathogenesis of Barrett's epithelium. MATERIALS AND METHODS: Immunohistochemistry was used to analyse the expression of KLF4, BMP4, CDX2, MUC2 and MUC5AC in human esophageal specimens. Human esophageal squamous epithelial cells were subjected to bile acid treatment and used in transfection experiments...
September 28, 2016: Experimental and Molecular Pathology
Ujjal K Bhawal, Ryoichiro Uchida, Noboru Kuboyama, Tetsuo Asakura, Koichi Hiratuska, Norihiro Nishiyama
Existing scaffolds cannot adequately satisfy the simultaneous requirements for the regeneration of bone. The challenge remains of how to improve the integration of newly formed bone with the surrounding tissues. The purpose of this study was to investigate the effects of two silk fibroin scaffolds, a hexafluoro isopropanol-based silk fibroin (HFIP-F) and an aqueous-based silk fibroin (A-F), for their osteoinductive potentials in large critical size bone defects in vivo. β-tricalcium phosphate (β-TCP) was used as a positive control...
September 28, 2016: Bio-medical Materials and Engineering
Xinjun Chen, Jing Xu, Baozhou Jiang, Danping Liu
BACKGROUND This aim of this study was to investigate the expression of BMP-7 in atrial fibrillation and illuminate the role of BMP-7 and TGF-β/Smads signaling in myocardial fibrosis. MATERIAL AND METHODS Fibrosis of myocardial fibroblasts was induced by TGF-β1 and the optimal condition was determined by the MTT assay. Cells with TGF-β1 treatment were sub-divided into 4 groups: TGF-β1 group, TGF-β1 + Smad3 siRNA group, TGF-β1 + BMP-7 group, and TGF-β1 + BMP-7 + Smad1/5 siRNA group. Cells were then analyzed by detecting the expression of epithelial cadherin (E-cadherin), collagen I, alpha smooth muscle cell actin (α-SMA), and activated Smads using Western blot...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Fumio Goto, Sei Kakinuma, Masato Miyoshi, Tomoyuki Tsunoda, Shun Kaneko, Ayako Sato, Yu Asano, Satoshi Otani, Seishin Azuma, Hiroko Nagata, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Yasuhiro Itsui, Mina Nakagawa, Yasuhiro Asahina, Mamoru Watanabe
AIM: Fetal hepatic stem/progenitor cells, called hepatoblasts, play central roles in liver organogenesis; however, molecular mechanisms regulating proliferation and terminal differentiation of such cells have not been completely elucidated. Bone morphogenetic protein-4 (BMP-4) is essential for the development of stem cells in various tissues, but its function in regulating the phenotype of hepatoblasts after mid-gestational fetal stage remains unclear. The aim of this study is to clarify a functional role for BMP-4 in proliferation and terminal differentiation of murine hepatoblasts in mid-gestational fetal livers...
September 27, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Osamu Imamura, Masaaki Arai, Minori Dateki, Kunio Takishima
Oligodendrocytes are the myelin-forming cells of the central nervous system. Oligodendrocyte loss and failure of myelin development result in serious human disorders, including multiple sclerosis. Previously, using oligodendrocyte progenitor cells, we have shown that donepezil, which is an acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease, stimulates myelin gene expression and oligodendrocyte differentiation. Here, we aimed to analyze the effects of donepezil on primary mouse embryonic neural stem cells (NSCs)...
September 24, 2016: Journal of Neurochemistry
Naoki Umemura, Emika Ohkoshi, Masamichi Tajima, Hirotaka Kikuchi, Tadashi Katayama, Hiroshi Sakagami
BACKGROUND: Dental pulp tissue contains many undifferentiated mesenchymal cells, which retain the ability to differentiate into mature cells. Induced pluripotent stem cells have been developed from various cell sources, including dental pulp-derived stem cells, and evaluated for potential application to regenerative therapy. Dental pulp tissues overexpress CD44, a cell-adhesion factor involved in the induction of mineralization. In this study, we investigated the effects of hyaluronan-a known CD44 ligand-on dental pulp stem cells (DPSCs)...
2016: Stem Cell Research & Therapy
Byul-Nim Ahn, Fatih Karadeniz, Chang-Suk Kong, Ki-Ho Nam, Mi-Soon Jang, Youngwan Seo, Han Seong Kim
Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE) from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 μM...
September 14, 2016: Marine Drugs
Chinmaya Mahapatra, Rajendra K Singh, Jung-Ju Kim, Kapil D Patel, Roman A Perez, Jun-Hyeog Jang, Hae-Won Kim
Providing an osteogenic stimulatory environment is a key strategy to construct stem cell-based bone-equivalent tissues. Here we design a stem cell delivering gel matrix made of collagen (Col) with bioactive glass nanocarriers (BGn) that incorporate osteogenic signaling molecule, fibroblast growth factor 18 (FGF18), a reservoir considered to cultivate and promote osteogenesis of mesenchymal stem cells (MSCs). The presence of BGn in the gel was shown to enhance the osteogenic differentiation of MSCs, possibly due to the therapeutic role of ions released...
October 4, 2016: ACS Applied Materials & Interfaces
Huang Fang, PeiWen Song, CaiLiang Shen, XiaoYing Liu, HaiTai Li
OBJECTIVES: In this study, we aimed to investigate the effect of bone mesenchymal stem cells (BMSCs) conditioned medium on BMP4-induced activation of the Smad signaling pathway during the process of neural stem cells differentiation. METHODS: We designed four experimental groups: (A) control group, (B) BMP-4 treatment group, (C) BMSC-CM group, and (D) BMSC-CM (BMSC-conditioned medium) combined with BMP-4 group. The expression of microtube-associated protein-2 (MAP-2) detected by immunocytochemical staining and western blot...
September 16, 2016: Neurological Research
Hak Chung, Dayong Wu, Donald Smith, Simin Nikbin Meydani, Sung Nim Han
High-fat diet (HFD)-induced obesity has been reported to result in low hepatic iron storage. In the current study, we tested the hypothesis that these obesity-related changes in hepatic iron status could be reversed by decreasing adiposity by feeding a low-fat diet. Five-week-old C57BL/6 mice were assigned to 3 groups: the LL group was fed a control diet for 31 weeks, the HH group was fed a HFD for 31 weeks, and the HL group was fed the HFD for 15 weeks and then switched to the control diet for 16 weeks. The fat mass of the HL group decreased by 3...
September 2016: Nutrition Research
Chevaun D Morrison, Tressa M Allington, Cheryl L Thompson, Hannah L Gilmore, Jenny C Chang, Ruth A Keri, William P Schiemann
We previously reported that constitutive c-Abl activity (CST-Abl) abrogates the tumorigenicity of triple-negative breast cancer cells through the combined actions of two cellular events: downregulated matrix metalloproteinase (MMP) and upregulated p21Waf1/Cip1 expression. We now find decreased c-Abl expression to be significantly associated with diminished relapse-fee survival in breast cancer patients, particularly those exhibiting invasive and basal phenotypes. Moreover, CST-Abl expression enabled 4T1 cells to persist innocuously in the mammary glands of mice, doing so by exhausting their supply of cancer stem cells...
September 8, 2016: Oncotarget
Yan-Fang Xie, Wen-Gui Shi, Jian Zhou, Yu-Hai Gao, Shao-Feng Li, Qing-Qing Fang, Ming-Gang Wang, Hui-Ping Ma, Ju-Fang Wang, Cory J Xian, Ke-Ming Chen
Pulsed electromagnetic fields (PEMFs) have been considered as a potential candidate for the prevention and treatment of osteoporosis, however, the mechanism of its action is still elusive. We have previously reported that 50Hz 0.6mT PEMFs stimulate osteoblastic differentiation and mineralization in a primary cilium- dependent manner, but did not know the reason. In the current study, we found that the PEMFs promoted osteogenic differentiation and maturation of rat calvarial osteoblasts (ROBs) by activating bone morphogenetic protein BMP-Smad1/5/8 signaling on the condition that primary cilia were normal...
September 10, 2016: Bone
Young-Dan Cho, Bong-Soo Kim, Chang-Seok Lee, Kyung-Hwa Kim, Yang-Jo Seol, Yong-Moo Lee, In-Chul Rhyu, Young Ku, Hyun-Mo Ryoo
BACKGROUND: In our previous studies, we demonstrated that a fibronectin (FN)-derived oligopeptide termed F20 stimulates osteoblast differentiation in vitro and bone formation in vivo. However, the fundamental molecular mechanism by which F20 stimulates osteogenesis remains unknown. Therefore, in this study we investigated the molecular mechanism underlying the effect of F20 in osteoblast differentiation. METHODS: The role of F20 in osteoblast differentiation was examined using the mouse bone-marrow-derived ST2 cell line...
September 13, 2016: Journal of Periodontology
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