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https://www.readbyqxmd.com/read/28427810/synthesis-of-novel-5-6-dehydrokawain-analogs-as-osteogenic-inducers-and-their-action-mechanisms
#1
Momochika Kumagai, Keisuke Nishikawa, Takashi Mishima, Izumi Yoshida, Masahiro Ide, Keiko Koizumi, Munetomo Nakamura, Yoshiki Morimoto
An imbalance between bone resorption by osteoclasts and bone formation by osteoblasts can cause bone loss and bone-related disease. In a previous search for natural products that increase osteogenic activity, we found that 5,6-dehydrokawain (1) from Alpinia zerumbet promotes osteoblastogenesis. In this study, we synthesized and evaluated series of 5,6-dehydrokawain analogs. Our structure-activity relationships revealed that alkylation of para or meta position of aromatic ring of 1 promote osteogenic activity...
April 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28426699/anti-il-20-monoclonal-antibody-inhibited-inflammation-and-protected-against-cartilage-destruction-in-murine-models-of-osteoarthritis
#2
Yu-Hsiang Hsu, Ya-Yu Yang, Man-Hsiang Huwang, Yun-Han Weng, I-Ming Jou, Po-Tin Wu, Tain-Yu Lin, Li-Wha Wu, Ming-Shi Chang
Osteoarthritis (OA) is a degenerative joint disease characterized by progressive destruction of articular cartilage. Interleukin (IL)-20 is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis. We investigated the role of IL-20 in OA and evaluated whether anti-IL-20 antibody (7E) treatment attenuates disease severity in murine models of surgery-induced OA. Immunohistochemical staining was used to detect IL-20 and its receptors expression in synovial tissue and cartilage from OA patients, and in OA synovial fibroblasts (OASFs) and chondrocytes (OACCs) from rodents with surgery-induced OA...
2017: PloS One
https://www.readbyqxmd.com/read/28426320/transient-exposure-to-androgens-induces-a-remarkable-self-sustained-quiescent-state-in-dispersed-prostate-cancer-cells
#3
Anh Thu Bui, Meng-Er Huang, Maryline Havard, Fanny Laurent-Tchenio, François Dautry, Thierry Tchenio
Cellular quiescence is a reversible cell growth arrest that is often assumed to require a persistence of non-permissive external growth conditions for its maintenance. In this work, we showed that androgen could induce a quiescent state that is self-sustained in a cell-autonomous manner through a "hit and run" mechanism in androgen receptor-expressing prostate cancer cells. This phenomenon required the set-up of a sustained redox imbalance and TGFβ/BMP signaling that were dependent on culturing cells at low density...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28424263/the-kielin-chordin-like-protein-kcp-attenuates-high-fat-diet-induced-obesity-and-metabolic-syndrome-in-mice
#4
Abdul Soofi, Katherine I Wolf, Margo P Emont, Nathan Qi, Gabriel Martinez-Santibanez, Edward Grimley, Wesam Ostwani, Gregory R Dressler
Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-beta superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The Kielin/chordin-like Protein (KCP) is a secreted regulator of the TGF-beta superfamily pathways that can inhibit both TGF-beta and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models...
April 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28423564/hypermethylation-of-the-chrdl1-promoter-induces-proliferation-and-metastasis-by-activating-akt-and-erk-in-gastric-cancer
#5
Yao-Fei Pei, Ya-Jing Zhang, Yao Lei, Ding-Wei Wu, Tong-Hui Ma, Xi-Qiang Liu
CHRDL1 (Chordin-like 1) is a secreted protein that acts as an antagonist of bone morphogenetic protein (BMP). BMP plays a role as an activator of BMP receptor II (BMPR II), which mediates extracellular to intracellular signal transmission and is involved in carcinogenesis and metastasis. Herein, we report that CHRDL1 expression was significantly down-regulated in gastric cancer tissues and associated with poor survival. Clinic-pathological parameters demonstrated a close relationship between low CHRDL1 expression and metastasis...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420447/ck2-1-a-bone-morphogenetic-protein-receptor-type-ia-mimetic-peptide-repairs-cartilage-in-mice-with-destabilized-medial-meniscus
#6
Hemanth Akkiraju, Padma Pradeepa Srinivasan, Xian Xu, Xinqiao Jia, Catherine B Kirn Safran, Anja Nohe
BACKGROUND: Osteoarthritis (OA) of the knee involves degeneration of articular cartilage of the diarthrodial joints. Current treatment options temporarily relieve the joint pain but do not restore the lost cartilage. We recently designed a novel bone morphogenetic protein receptor type I (BMPRI) mimetic peptide, CK2.1, that activates BMPRIa signaling in the absence of bone morphogenetic protein (BMP). Our previous research demonstrated that CK2.1 induced chondrogenesis in vitro and in vivo; however, it is unknown if CK2...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28419135/an-organotypic-slice-culture-to-study-the-formation-of-calyx-of-held-synapses-in-vitro
#7
Elin Kronander, Nicolas Michalski, Cécile Lebrand, Jean-Pierre Hornung, Ralf Schneggenburger
The calyx of Held, a large axo-somatic relay synapse containing hundreds of presynaptic active zones, is possibly the largest nerve terminal in the mammalian CNS. Studying its initial growth in-vitro might provide insights into the specification of synaptic connection size in the developing brain. However, attempts to maintain calyces of Held in organotypic cultures have not been fruitful in past studies. Here, we describe an organotypic slice culture method in which calyces of Held form in-vitro. We made coronal brainstem slices with an optimized slice angle using newborn mice in which calyces have not yet formed; the presynaptic bushy cells were genetically labeled using the Math5 promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28415132/genetic-alterations-in-mesiodens-as-revealed-by-targeted-ngs-and-gene-co-occurrence-network-analysis
#8
Young Youn Kim, Jihye Hwang, Hye-Sung Kim, Hee Jun Kwon, Sanguk Kim, Ji Hyun Lee, Jae Hoon Lee
OBJECTIVE: Mesiodens is the most common type of supernumerary tooth which includes a population prevalence of 0.15-1.9%. Alongside evidence that the condition is heritable, mutations in single genes have been reported in few human supernumerary tooth cases. Gene sequencing methods in tradition way are time-consuming and labor-intensive, whereas next generation sequencing and bioinformatics are cost-effective for large samples and target sizes. MATERIALS AND METHODS: We describe the application of a targeted next generation sequencing (NGS) and bioinformatics approach to samples from 17 mesiodens patients...
April 17, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28403520/study-of-gene-expression-alteration-in-male-androgenetic-alopecia-evidence-of-predominant-molecular-signaling-pathways
#9
L Michel, P Reygagne, P Benech, F Jean-Louis, S Scalvino, S Ly Ka So, Z Hamidou, S Bianovici, J Pouch, B Ducos, M Bonnet, A Bensussan, A Patatian, E Lati, J Wdzieczak-Bakala, J-C Choulot, E Loing, M Hocquaux
BACKGROUND: Male androgenetic alopecia (AGA) is the most common form of hair loss in men and is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined. OBJECTIVES: Herein, molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless/bald men with premature AGA and healthy volunteers...
April 12, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28401685/characterization-of-new-bone-morphogenetic-protein-bmp-2-regulatory-alleles
#10
Tapan A Shah, Youhua Zhu, Nadia N Shaikh, Marie A Harris, Stephen E Harris, Melissa B Rogers
Bone morphogenetic protein 2 (BMP2, HGNC:1069, GeneID: 650) is a classical morphogen; a molecule that acts at a distance and whose concentration influences cell proliferation, differentiation, and apoptosis. Key events requiring precise Bmp2 regulation include heart specification and morphogenesis and neural development. In mesenchymal cells, the concentration of BMP2 influences myogenesis, adipogenesis, chondrogenesis, and osteogenesis. Because the amount, timing, and location of BMP2 synthesis influence pattern formation and organogenesis, the mechanisms that regulate Bmp2 are crucial...
April 12, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28396518/rapamycin-efficiently-promotes-cardiac-differentiation-of-mouse-embryonic-stem-cells
#11
Qin Lu, Zhuqing Jia, Yang Wang, Weiping Wang, Zhe Yang, Tao Li, Yuyao Tian, Ping Chen, Kangtao Ma, Yinan Liu, Chunyan Zhou
To investigate the effects of the rapamycin on cardiac differentiation, murine ESCs was induced to cardiomyocytes by 10(-4) M ascorbic acid (AA), 20 nM rapamycin alone or 0.1‰ solvent dimethyl sulfoxide (DMSO). We found that rapamycin alone was insufficient to initiate cardiomyogenesis. Then the ESCs was treated with AA and rapamycin (20 nM) or AA and DMSO (0.1‰) as a control. Compared with control, mESCs treated with rapamycin (20 nM) and AA yielded a significantly higher percentage of cardiomyocytes, as confirmed by percentage of beating EBs, the immunofluorescence and FACS analysis...
April 10, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28391780/clinical-significance-linked-to-functional-defects-in-bone-morphogenetic-protein-type-2-receptor-bmpr2
#12
Myung-Jin Kim, Seon Young Park, Hae Ryung Chang, Eun Young Jung, Anudari Munkhjargal, Jong-Seok Lim, Myeong-Sok Lee, Yonghwan Kim
Bone morphogenetic protein type 2 receptor (BMPR2) is one of the transforming growth factor-β (TGF-β) superfamily receptors, playing diverse roles during embryonic development, vasculogenesis, and osteogenesis. Human BMPR2 consists of 1,038 amino acids and contains functionally conserved extracellular, transmembrane, kinase, and C-terminal cytoplasmic domains. Bone morphogenetic proteins (BMPs) engage the tetrameric complex, composed of BMPR2 and its corresponding type 1 receptors, which initiates SMAD family of proteins-mediated signal transduction leading to expression of target genes implicated in development or differentiation of the embryo, organs and bones...
April 10, 2017: BMB Reports
https://www.readbyqxmd.com/read/28389839/p15-peptide-stimulates-chondrogenic-commitment-and-endochondral-ossification
#13
Jun Zhang, Peter Eisenhauer, Ozҫan Kaya, Alexander R Vaccaro, Carol Diallo, Andrzej Fertala, Theresa A Freeman
PURPOSE: The synthetic 15 amino acid biomimetic peptide sequence (P15) derived from a region of the alpha (α)-1 chain of collagen I, has been shown to promote α2 integrin activation and enhance intramembranous ossification. In this study, we ask if the P15 peptide also enhances bone formation through endochondral ossification, and determine if direct binding of α2 integrin with P15 mediates integrin activation. METHODS: Mesenchymal cells (C3H10T1/2) were cultured in chondrogenic media and the expression of chondrogenic markers and integrin activation was determined by Western blot and fluorescent immunohistochemistry...
April 8, 2017: International Orthopaedics
https://www.readbyqxmd.com/read/28389444/bone-morphogenetic-protein-based-therapeutic-approaches
#14
Jonathan W Lowery, Vicki Rosen
Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor (TGF)-β family of ligands and exert most of their effects through the canonical effectors Smad1, 5, and 8. Appropriate regulation of BMP signaling is critical for the development and homeostasis of numerous human organ systems. Aberrations in BMP pathways or their regulation are increasingly associated with diverse human pathologies, and there is an urgent and growing need to develop effective approaches to modulate BMP signaling in the clinic...
April 7, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28387157/bone-morphogenetic-protein-9-increases-the-functional-expression-of-organic-anion-transporting-polypeptide-1a4-at-the-blood-brain-barrier-via-the-activin-receptor-like-kinase-1-receptor
#15
Wazir Abdullahi, Hrvoje Brzica, Kathryn Ibbotson, Thomas P Davis, Patrick T Ronaldson
Targeting uptake transporters such as organic anion transporting polypeptide 1a4 (Oatp1a4) at the blood-brain barrier (BBB) can facilitate central nervous system (CNS) drug delivery. Effective blood-to-brain drug transport via this strategy requires characterization of mechanisms that modulate BBB transporter expression and/or activity. Here, we show that activation of activin receptor-like kinase (ALK)-1 using bone morphogenetic protein (BMP)-9 increases Oatp1a4 protein expression in rat brain microvessels in vivo...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28386343/signaling-by-tgf-betas-in-tubule-cultures-of-adult-rat-testis
#16
Kai-Hui Chan, Sebastian P Galuska, Pradeep Kumar Kudipudi, Mohammad Assad Riaz, Kate L Loveland, Lutz Konrad
Although signal transduction of transforming growth factor-betas (TGF-βs) is well characterized in individual cell types, data about TGF-β signaling in a cellular context is still scarce. In this study, we used ex vivo tubule cultures from adult rat testis to investigate TGF-β signaling. We show for the first time in testicular tubules, that TGF-βs also signal via the BMP type I receptors, with ALK2 used by TGF-β1 and ALK3 and ALK6 by TGF-β2. This signal transduction is mediated via Smad3 as well as via Smad1...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28381236/microglia-activation-is-essential-for-bmp7-mediated-retinal-reactive-gliosis
#17
Subramanian Dharmarajan, Debra L Fisk, Christine M Sorenson, Nader Sheibani, Teri L Belecky-Adams
BACKGROUND: Our previous studies have shown that BMP7 is able to trigger activation of retinal macroglia. However, these studies showed the responsiveness of Müller glial cells and retinal astrocytes in vitro was attenuated in comparison to those in vivo, indicating other retinal cell types may be mediating the response of the macroglial cells to BMP7. In this study, we test the hypothesis that BMP7-mediated gliosis is the result of inflammatory signaling from retinal microglia. METHODS: Adult mice were injected intravitreally with BMP7 and eyes harvested 1, 3, or 7 days postinjection...
April 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28364348/analysis-of-soluble-factors-in-conditioned-media-derived-from-primary-cultures-of-cirrhotic-liver-of-biliary-atresia
#18
Taisuke Yamazaki, Mariko Wakai, Shin Enosawa, Takayoshi Tokiwa
Biliary atresia (BA) is a rare and serious liver disease in newborn infants. Previously, we reported that non-parenchymal cell (NPC) fractions from cirrhotic liver of BA may contain hepatic stem/progenitor cells in primary culture of NPC fractions. In this study, NPC fractions were subjected to primary or passage culture and found that clusters of hepatocyte-like cells appear even without adding hepatocyte growth factor (HGF) to the culture medium, but not in their passage culture used as a control. Based on these findings, conditioned media (CMs) were collected and soluble factors in the CMs were analyzed in order to elucidate the mechanism of the appearance of hepatocyte-like cells or their clusters...
March 31, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28361317/generation-of-gastrointestinal-organoids-from-human-pluripotent-stem-cells
#19
Jorge O Múnera, James M Wells
Over the past several decades, developmental biologists have discovered fundamental mechanisms by which organs form in developing embryos. With this information it is now possible to generate human "organoids" by the stepwise differentiation of human pluripotent stem cells using a process that recapitulates organ development. For the gastrointestinal tract, one of the first key steps is the formation of definitive endoderm and mesoderm, a process that relies on the TGFb molecule Nodal. Endoderm is then patterned along the anterior-posterior axis, with anterior endoderm forming the foregut and posterior endoderm forming the mid and hindgut...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28361311/directed-differentiation-of-mouse-embryonic-stem-cells-into-inner-ear-sensory-epithelia-in-3d-culture
#20
Jing Nie, Karl R Koehler, Eri Hashino
The inner ear sensory epithelium harbors mechanosensory hair cells responsible for detecting sound and maintaining balance. This protocol describes a three-dimensional (3D) culture system that efficiently generates inner ear sensory epithelia from aggregates of mouse embryonic stem (mES) cells. By mimicking the activations and repressions of key signaling pathways during in vivo inner ear development, mES cell aggregates are sequentially treated with recombinant proteins and small molecule inhibitors for activating or inhibiting the Bmp, TGFβ, Fgf, and Wnt signaling pathways...
2017: Methods in Molecular Biology
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