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https://www.readbyqxmd.com/read/29780169/mediator-kinase-cdk8-cdk19-drives-yap1-dependent-bmp4-induced-emt-in-cancer
#1
Anne Serrao, Laura M Jenkins, Alexander A Chumanevich, Ben Horst, Jiaxin Liang, Michael L Gatza, Nam Y Lee, Igor B Roninson, Eugenia V Broude, Karthikeyan Mythreye
CDK8 is a transcription-regulating kinase that controls TGF-β/BMP-responsive SMAD transcriptional activation and turnover through YAP1 recruitment. However, how the CDK8/YAP1 pathway influences SMAD1 response in cancer remains unclear. Here we report that SMAD1-driven epithelial-to-mesenchymal transition (EMT) is critically dependent on matrix rigidity and YAP1 in a wide spectrum of cancer models. We find that both genetic and pharmacological inhibition of CDK8 and its homologous twin kinase CDK19 leads to abrogation of BMP-induced EMT...
May 21, 2018: Oncogene
https://www.readbyqxmd.com/read/29778895/therapeutic-antibody-directed-osteogenic-differentiation-of-induced-pluripotent-stem-cells-derived-mscs
#2
Qingqing Wu, Bo Yang, Cong Cao, Kevin Hu, Ping Wang, Yi Man
Induced pluripotent stem cells (iPSCs) are regarded as a new cell source for regenerative medicine. Recent advances in tissue engineering have brought to light the therapeutic application of induced pluripotent stem cells (iPSCs) in bone defect repair. However, a safe and efficient way to differentiate iPSCs into osteogenic lineage remains to be a major challenge. Here we describe an approach using anti-BMP2 antibodies (Abs) to mediate osteogenic differentiation of iPSC-derived mesenchymal stromal cells (iMSCs)...
May 17, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29758548/stromal-cell-derived-factor-sdf-1-alpha-overexpression-promotes-bone-regeneration-by-osteogenesis-and-angiogenesis-in-osteonecrosis-of-the-femoral-head
#3
Fan Yang, Feng Xue, Junjie Guan, Zeng Zhang, Jimin Yin, Qingling Kang
BACKGROUND/AIMS: Osteonecrosis of the femoral head (ONFH) is a devastating orthopedic disease. Previous studies suggested that stromal-cell-derived factor (SDF)-1 was involved in osteogenesis and angiogenesis. However, whether SDF-1 potentiates the angiogenesis and osteogenesis of bone marrow-derived stromal stem cells (BMSCs) in ONFH is not clear. METHODS: BMSCs were transfected with green fluorescent protein (GFP) or the fusion gene encoding GFP and SDF-1α, and transgenic efficacy was monitored by immunofluorescence...
May 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29753378/microrna-140-suppresses-human-chondrocytes-hypertrophy-by-targeting-smad1-and-controlling-the-bone-morphogenetic-protein-pathway-in-osteoarthritis
#4
Canfeng Li, Qinshen Hu, Zhuo Chen, Bin Shen, Jing Yang, Pengde Kang, Zongke Zhou, Fuxing Pei
BACKGROUND: This study aimed to investigate the expression levels and relationship of bone morphogenetic proteins (BMPs) signaling molecules and microRNA-140 (miR-140) in human osteoarthritis (OA) chondrocytes. MATERIALS AND METHODS: Different stage chondrocytes (normal cartilage, mid-stage OA and advanced-stage OA) were isolated from cartilage samples according to Kellgren and Lawrence criteria. The effect of miR-140 on BMPs signaling was evaluated by transfecting miR-140 mimic or inhibitor into chondrocytes...
May 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29751359/bone-morphogenetic-protein-9-as-a-key-regulator-of-liver-progenitor-cells-in-ddc-induced-cholestatic-liver-injury
#5
Annalisa Addante, Cesáreo Roncero, Laura Almalé, Nerea Lazcanoiturburu, María García-Álvaro, Margarita Fernández, Julián Sanz, Seddik Hammad, Zeribe Chike Nwosu, Se-Jin Lee, Isabel Fabregat, Steven Dooley, Peter Ten Dijke, Blanca Herrera, Aránzazu Sánchez
BACKGROUND & AIMS: Bone morphogenetic protein 9 (BMP9) interferes with liver regeneration upon acute injury, while promoting fibrosis upon carbon tetrachloride-induced chronic injury. We have now addressed the role of BMP9 in 3,5 diethoxicarbonyl-1,4 dihydrocollidine (DDC)-induced cholestatic liver injury, a model of liver regeneration mediated by hepatic progenitor cell (known as oval cell), exemplified as ductular reaction and oval cell expansion. METHODS: WT and BMP9KO mice were submitted to DDC diet...
May 11, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29750278/bmp6-down-regulates-gdnf-expression-through-smad1-5-and-erk1-2-signaling-pathways-in-human-granulosa-lutein-cells
#6
Xin-Yue Zhang, Hsun-Ming Chang, Elizabeth L Taylor, Peter C K Leung, Rui-Zhi Liu
Bone morphogenetic protein 6 (BMP6) is a critical regulator of follicular development that is expressed in mammalian oocytes and granulosa cells. Glial cell line-derived neurotrophic factor (GDNF) is an intraovarian neurotrophic factor that plays an essential role in regulating mammalian oocyte maturation. The aim of this study was to investigate the effect of BMP6 on the regulation of GDNF expression and the potential underlying mechanisms. We used an established immortalized human granulosa cell line (SVOG cells) and primary human granulosa-lutein cells as in vitro cell models...
May 9, 2018: Endocrinology
https://www.readbyqxmd.com/read/29739878/bmpr2-inhibits-activin-and-bmp-signaling-via-wild-type-alk2
#7
Oddrun Elise Olsen, Meenu Sankar, Samah Elsaadi, Hanne Hella, Glenn Buene, Sagar Ramesh Darvekar, Kristine Misund, Takenobu Katagiri, Petra Knaus, Toril Holien
TGF-β/BMP superfamily ligands require heteromeric complexes of type 1 and 2 receptors for ligand dependent downstream signaling. Activin A, a TGF-β superfamily member, inhibits growth of multiple myeloma cells, but the mechanism is unknown. We aimed to clarify how activins affect myeloma cell survival. Activin A activates the transcription factors SMAD2/3 through the ALK4 type 1 receptor, but may also activate SMAD1/5/8 through mutated variants of the type 1 receptor ALK2. We demonstrate that activin A and B activate SMAD1/5/8 in myeloma cells through endogenous wild type ALK2...
May 8, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29736392/quercetin-stimulates-bone-marrow-mesenchymal-stem-cell-differentiation-through-an-estrogen-receptor-mediated-pathway
#8
Xin-Gang Pang, Yu Cong, Ni-Rong Bao, Yong-Gang Li, Jian-Ning Zhao
Objectives: The present study aimed to investigate the overall effect of quercetin on mouse bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation in vitro . Materials and Methods: BMSCs were treated with different concentrations of quercetin for 6 days. The effects of quercetin on cell proliferation were assessed at predetermined times using Cell Counting Kit-8 (CCK-8) assay. The cells were then treated with quercetin, estrogen, or an estrogen receptor (ER) antagonist (which was also administered in the presence of quercetin or estrogen) for 7 or 21 days...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29736214/masquelet-s-induced-membrane-promotes-the-osteogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-by-activating-the-smad-and-mapk-pathways
#9
Qian Tang, Minji Tong, Gang Zheng, Liyan Shen, Ping Shang, Haixiao Liu
The Masquelet's induced membrane (IM) technique is widely used to treat large segmental bone defects due to its physical priority and biological function. However, the underlying molecular mechanism of the IM on bone formation remains unknown. In the present study, rat bone marrow-derived mesenchymal stem cells (BMSCs) were used as an in vitro model and bone morphogenetic protein 2 (BMP-2) was used as a positive control to evaluate the effects of the IM on the osteogenic differentiation of BMSCs. Although the IM group did not exhibit a significant increase in the expression of Runt-related transcription factor 2 (Runx2), Collagen I (Col I), osteocalcin (OCN) and alkaline phosphatase (ALP) relative to the BMP-2 administration, the IM was considerably effective compared with the untreated group...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29731966/-in-vitro-study-on-role-of-%C3%AF-b-protein-in-avian-reovirus-pathogenesis
#10
Manas R Praharaj, Aditya P Sahoo, Tapan K S Chauhan, Ravi Kumar Gandham, Shikha Saxena, Ravi K Agarwal, Kuldeep Dhama, Bina Mishra, Asok K Marriappan, Ashok K Tiwari, Puroshottam Prasad Goswami, Bishnu Prasad Mishra, Deepak Kumar
Avian reoviruses, members of Orthoreovirus genus was known to cause diseases like tenosynovitis, runting-stunting syndrome in chickens. Among eight structural proteins, the proteins of S-class are mainly associated with viral arthritis but the significance of σB protein in arthritis is not established till date. In this infection pathological condition together with infection of joints often leads to arthritis because joints consists of cartilage which forms lubricating surface between two bones, and has limited metabolic, replicative and repair capacity...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29729706/tgf%C3%AE-1-mediated-pi3k-akt-and-p38-map-kinase-dependent-alternative-splicing-of-fibronectin-extra-domain-a-in-human-podocyte-culture
#11
Tarunkumar Hemraj Madne, Mark Edward Carl Dockrell
Alternative splicing is an important gene regulation process to distribute proteins in health and diseases. Extra Domain A+ Fibronectin (EDA+Fn) is an alternatively spliced form of fibronectin (Fn) protein, present in the extra cellular matrix (ECM) and a recognised marker of various pathologies. TGFβ1 has been shown to induce alternative splicing of EDA+Fn in many cell types. Podocytes are spectacular cell type and play a key role in filtration and synthesise ECM proteins in renal physiology and pathology...
April 30, 2018: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29728612/identification-of-the-effector-domain-of-biglycan-that-facilitates-bmp-2-osteogenic-function
#12
Prapaporn Jongwattanapisan, Masahiko Terajima, Patricia A Miguez, William Querido, Hideaki Nagaoka, Noriko Sumida, Elizabeth Grace Gurysh, Kristy M Ainslie, Nancy Pleshko, Lalith Perera, Mitsuo Yamauchi
We have reported that recombinant biglycan (BGN) core protein accelerates bone formation in vivo by enhancing bone morphogenetic protein (BMP)-2 function. The purpose of the present study was to identify the specific domain ("effector") within the BGN core protein that facilitates BMP-2 osteogenic function. Thus, we generated various recombinant and synthetic peptides corresponding to several domains of BGN, and tested their effects on BMP-2 functions in vitro. The results demonstrated that the leucine-rich repeats 2-3 domain (LRR2-3) of BGN significantly enhanced the BMP-2 induced Smad1/5/9 phosphorylation, osteogenic gene expression, and alkaline phosphatase activity in myogenic C2C12 cells...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29715457/spg6-supports-development-of-acute-myeloid-leukemia-by-regulating-bmpr2-smad-bcl-2-bcl-xl-signaling
#13
Jinliang Chen, Chunling Li, Renhui Zhan, Yancun Yin
Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. To effectively treat AML, new molecular targets and therapeutic approaches must be identified. In silico analysis of several available databases of AML patients showed that the expression of Spastic Paraplegia 6 Protein (SPG6) significantly inversely correlates with the overall survival of AML patients. To determine whether SPG6 supports AML development, we employed an shRNA-encoding lentivirus system to inhibit SPG6 expression in human AML cells including NB4 and MV4-11 cells...
April 28, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29700355/claudin-11-regulates-bone-homeostasis-via-bidirectional-ephb4-ephrinb2-signaling
#14
Jong Min Baek, Yoon-Hee Cheon, Sung Chul Kwak, Hong Young Jun, Kwon-Ha Yoon, Myeung Su Lee, Ju-Young Kim
Claudins (Cldns) are well-established components of tight junctions (TJs) that play a pivotal role in the modulation of paracellular permeability. Several studies have explored the physiologic aspects of Cldn family members in bone metabolism. However, the effect of Cldn11, a major component of central nervous system myelin, on bone homeostasis has not been reported. In this study, we demonstrate that Cldn11 is a potential target for bone disease therapeutics as a dual modulator of osteogenesis enhancement and osteoclastogenesis inhibition...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29692799/genome-wide-association-analyses-highlight-the-potential-for-different-genetic-mechanisms-for-litter-size-among-sheep-breeds
#15
Song-Song Xu, Lei Gao, Xing-Long Xie, Yan-Ling Ren, Zhi-Qiang Shen, Feng Wang, Min Shen, Emma Eyϸórsdóttir, Jón H Hallsson, Tatyana Kiseleva, Juha Kantanen, Meng-Hua Li
Reproduction is an important trait in sheep breeding as well as in other livestock. However, despite its importance the genetic mechanisms of litter size in domestic sheep ( Ovis aries ) are still poorly understood. To explore genetic mechanisms underlying the variation in litter size, we conducted multiple independent genome-wide association studies in five sheep breeds of high prolificacy (Wadi, Hu, Icelandic, Finnsheep, and Romanov) and one low prolificacy (Texel) using the Ovine Infinium HD BeadChip, respectively...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29686106/embryonic-regeneration-by-relocalization-of-the-spemann-organizer-during-twinning-in-xenopus
#16
Yuki Moriyama, Edward M De Robertis
The formation of identical twins from a single egg has fascinated developmental biologists for a very long time. Previous work had shown that Xenopus blastulae bisected along the dorsal-ventral (D-V) midline (i.e., the sagittal plane) could generate twins but at very low frequencies. Here, we have improved this method by using an eyelash knife and changing saline solutions, reaching frequencies of twinning of 50% or more. This allowed mechanistic analysis of the twinning process. We unexpectedly observed that the epidermis of the resulting twins was asymmetrically pigmented at the tailbud stage of regenerating tadpoles...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29677202/%C3%AE-1-integrins-mediate-the-bmp2-dependent-transcriptional-control-of-osteoblast-differentiation-and-osteogenesis
#17
Molly Brunner, Noémie Mandier, Thierry Gautier, Genevieve Chevalier, Anne-Sophie Ribba, Philippe Guardiola, Marc R Block, Daniel Bouvard
Osteoblast differentiation is a highly regulated process that requires coordinated information from both soluble factors and the extracellular matrix. Among these extracellular stimuli, chemical and physical properties of the matrix are sensed through cell surface receptors such as integrins and transmitted into the nucleus to drive specific gene expression. Here, we showed that the conditional deletion of β1 integrins in the osteo-precursor population severely impacts bone formation and homeostasis both in vivo and in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29664133/coordinated-regulation-of-the-dorsal-ventral-and-anterior-posterior-patterning-of-xenopus-embryos-by-the-btb-poz-zinc-finger-protein-zbtb14
#18
Kimiko Takebayashi-Suzuki, Hidenori Konishi, Tatsuo Miyamoto, Tomoko Nagata, Misa Uchida, Atsushi Suzuki
During early vertebrate embryogenesis, bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-β (TGF-β) family of growth factors play a central role in dorsal-ventral (DV) patterning of embryos, while other growth factors such as Wnt and fibroblast growth factor (FGF) family members regulate formation of the anterior-posterior (AP) axis. Although the establishment of body plan is thought to require coordinated formation of the DV and AP axes, the mechanistic details underlying this coordination are not well understood...
April 2018: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/29663368/a-peptide-that-blocks-the-interaction-of-nf-%C3%AE%C2%BAb-p65-subunit-with-smad4-enhances-bmp2-induced-osteogenesis
#19
Mariko Urata, Shoichiro Kokabu, Takuma Matsubara, Goro Sugiyama, Chihiro Nakatomi, Hiroshi Takeuchi, Shizu Hirata-Tsuchiya, Kazuhiro Aoki, Yukihiko Tamura, Yasuko Moriyama, Yasunori Ayukawa, Miho Matsuda, Min Zhang, Kiyoshi Koyano, Chiaki Kitamura, Eijiro Jimi
Bone morphogenetic protein (BMP) potentiates bone formation through the Smad signaling pathway in vitro and in vivo. The transcription factor nuclear factor κB (NF-κB) suppresses BMP-induced osteoblast differentiation. Recently, we identified that the transactivation (TA) 2 domain of p65, a main subunit of NF-κB, interacts with the mad homology (MH) 1 domain of Smad4 to inhibit BMP signaling. Therefore, we further attempted to identify the interacting regions of these two molecules at the amino acid level...
April 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29651293/homeobox-a5-promotes-white-adipose-tissue-browning-through-inhibition-of-the-tenascin-c-toll-like-receptor-4-nuclear-factor-kappa-b-inflammatory-signaling-in-mice
#20
Weina Cao, Hongtao Huang, Tianyu Xia, Chenlong Liu, Saeed Muhammad, Chao Sun
Lipopolysaccharide (LPS) induces rapid increase in systemic inflammatory factors. As adipose tissue is a key contributor to the inflammatory response to numerous metabolic stimuli, it is important to understand the mechanism behind the LPS-induced inflammation in white adipose tissue (WAT). Homeobox a5 (Hoxa5) is an important transcription factor, which is highly expressed in adipose tissue, and its mRNA expression is increased at cold exposure in mice. So far, the function of Hoxa5 in adipose tissue browning has been poorly understood...
2018: Frontiers in Immunology
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