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https://www.readbyqxmd.com/read/28934877/activin-and-nodal-are-not-suitable-alternatives-to-tgf%C3%AE-for-chondrogenic-differentiation-of-mesenchymal-stem-cells
#1
Laurie M G de Kroon, Esmeralda N Blaney Davidson, Roberto Narcisi, Eric Farrell, Peter M van der Kraan, Gerjo J V M van Osch
Objective Previously, we demonstrated the importance of transforming growth factor-β (TGFβ)-activated SMAD2/3 signaling in chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). However, TGFβ also signals via the SMAD1/5/9 pathway, which is known to induce terminal differentiation of BMSCs. In this study, we investigated whether other SMAD2/3-activating ligands, Activin and Nodal, can induce chondrogenic differentiation of BMSCs without inducing terminal differentiation. Design Activation of SMAD2/3 signaling and chondrogenesis were evaluated in human BMSCs ( N = 3 donors) stimulated with TGFβ, Activin, or Nodal...
October 2017: Cartilage
https://www.readbyqxmd.com/read/28926103/fam20c-regulates-osteoblast-behaviors-and-intracellular-signaling-pathways-in-a-cell-autonomous-manner
#2
Chao Liu, Hua Zhang, Priyam Jani, Xiaofang Wang, Yongbo Lu, Nan Li, Jing Xiao, Chunlin Qin
Recent studies indicate that Family with sequence similarity 20 member C (FAM20C) catalyzes the phosphorylation of secreted proteins, and participates in a variety of biological processes, including cell proliferation, migration, mineralization and phosphate homeostasis. To explore the local influences of FAM20C on osteoblast, Fam20c-deficient osteoblasts were generated by treating the immortalized Fam20c(f/f) osteoblasts with CMV-Cre-IRES-EGFP lentivirus. Compared with the normal Fam20c(f/f) osteoblasts, the expression of Bone sialoprotein (Bsp), Osteocalcin (Ocn), Fibroblast growth factor 23 (Fgf23) and transcription factors that promote osteoblast maturation were up-regulated in the Fam20c-deficient osteoblasts...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28926099/anti-osteoporosis-activity-of-sanguinarine-in-preosteoblast-mc3t3-e1-cells-and-an-ovariectomized-rat-model
#3
Fuzhan Zhang, Jile Xie, Genlin Wang, Ge Zhang, Huilin Yang
Sanguinarine, a benzophenanthridine alkaloid, has been previously demonstrated to exert antimicrobial, anti-inflammatory and anti-tumor activities. A previous study has identified Sanguinarine as a potential drug candidate for osteoporosis treatment by computational bioinformatics analysis. This study further evaluated the effects of Sanguinarine on the differentiation of murine preosteoblast MC3T3-E1 cells and its anti-osteoporosis activity in an ovarietomized rat model. Sanguinarine treatment (0.25, 0.5, 1 and 2 µM) of MC3T3-E1 cells significantly increased alkaline phosphatase (ALP) activity and the phoshporalyation of AMP-activated protein kinase α subunit (AMPKα), but did not affect cell proliferation...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28923783/bmp7-induced-pten-inhibits-akt-and-prevents-renal-fibrosis
#4
Debra F Higgins, Leah Ewart, Enda Masterson, Sadhbh Tennant, Gleb Grebnev, Marco Prunotto, Sylvia Pomposiello, Karin Conde-Knape, Finian M Martin, Catherine Godson
Bone morphogenetic protein-7 (BMP-7) counteracts pro-fibrotic effects of TGFβ1 in cultured renal cells and protects from fibrosis in acute and chronic renal injury models. Using the unilateral ureteral obstruction (UUO) model of chronic renal fibrosis, we investigated the effect of exogenous-rhBMP-7 on pro-fibrotic signaling pathways mediated by TGFβ1 and hypoxia. Mice undergoing UUO were treated with vehicle or rhBMP-7 (300μg/kg i.p.) every other day for eight days and kidneys analysed for markers of fibrosis and SMAD, MAPK, and PI3K signaling...
September 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28921936/sprouty2-is-involved-in-the-control-of-osteoblast-proliferation-and-differentiation-through-the-fgf-and-bmp-signaling-pathways
#5
Takaharu Taketomi, Tomohiro Onimura, Daigo Yoshiga, Daichi Muratsu, Terukazu Sanui, Takao Fukuda, Jingo Kusukawa, Seiji Nakamura
Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) play essential roles in bone formation and osteoblast activity through the extracellular signal regulated kinase 1/2 (ERK1/2) and Smad pathways. Sprouty family members are intracellular inhibitors of the FGF signaling pathway, and four orthologs of Sprouty have been identified in mammals. In vivo analyses have revealed that Sprouty2 is associated with bone formation. However, the mechanism by which the Sprouty family controls bone formation has not been clarified...
September 16, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28903487/from-the-cover-arsenic-induces-hippocampal-neuronal-apoptosis-and-cognitive-impairments-via-an-up-regulated-bmp2-smad-dependent-reduced-bdnf-trkb-signaling-in-rats
#6
Rukmani Pandey, Vipin Rai, Juhi Mishra, Kapil Mandrah, Somendu Kumar Roy, Sanghamitra Bandyopadhyay
Arsenic promotes hippocampal neuronal damage inducing cognitive impairments. However, mechanism arbitrating arsenic-mediated cognitive deficits remains less-known. Here, we identified that chronic exposure to environmentally relevant doses of arsenic increased apoptosis, characterized by caspase-3 activation, poly(ADP-ribose) polymerase cleavage and Terminal deoxynucleotidyl transferase dUTP nick-end labeling of rat hippocampal neurons, marked by NeuN. Investigating apoptotic mechanism through invivo and invitro studies revealed that arsenic promoted bone morphogenetic protein-2 (BMP2) expression, supported by increased BMP-receptor2 (BMPR2) and p-Smad1/5 in hippocampal neurons...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28893092/salvianolic-acid-a-a-component-of-salvia-miltiorrhiza-attenuates-endothelial-mesenchymal-transition-of-hpaecs-induced-by-hypoxia
#7
Tianyi Yuan, Yucai Chen, Huifang Zhang, Lianhua Fang, Guanhua Du
Salvianolic acid A (SAA), a polyphenols acid, is a bioactive ingredient from a traditional Chinese medicine called Dan shen (Salvia Miltiorrhiza Bunge). According to previous studies, it was shown to have various effects such as anti-oxidative stress, antidiabetic complications and antipulmonary hypertension. This study aimed to investigate the effect of SAA on pulmonary arterial endothelial-mesenchymal transition (EndoMT) induced by hypoxia and the underlying mechanisms. Primary cultured human pulmonary arterial endothelial cells (HPAECs) were exposed to 1% O2 for 48[Formula: see text]h with or without SAA treatment...
2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28881744/mir-199a-3p-suppresses-proliferation-and-invasion-of-prostate-cancer-cells-by-targeting-smad1
#8
Feng Qu, Jinyu Zheng, Weidong Gan, Huibo Lian, Hua He, Wuping Li, Tian Yuan, Yaling Yang, Xiaogong Li, Changwei Ji, Xiang Yan, Linfeng Xu, Hongqian Guo
OBJECTIVES: This study was intended to analyze effects of miR-199a-3p and Smad1 on proliferation, migration and invasion of prostate cancer (PCa) cells. RESULTS: MiR-199a-3p was significantly decreased in PCa tissues in comparison to that in adjacent normal tissues (P < 0.05). Over-expressed miR-199a-3p markedly suppressed proliferation and invasion of PCa cells (P < 0.05). MiR-199a-3p was negatively correlated with Smad1 expression, and overexpression of Smad1 could antagonize the effects of miR-199a-3p on PCa cells...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881580/selective-compounds-enhance-osteoblastic-activity-by-targeting-hect-domain-of-ubiquitin-ligase-smurf1
#9
Yuan Zhang, Cheng Wang, Yu Cao, Yongqing Gu, Lingqiang Zhang
The HECT-type ubiquitin ligase Smurf1 (Smad ubiquitination regulatory factor-1) plays the prominent role in regulation of bone formation, embryonic development, and tumorigenesis by directing the ubiquitin-proteasomal degradation of specific targets. In contrast with RING-type E3s, the catalytic HECT domain of Smurf1 firstly binds to and then transfers ubiquitin (Ub) molecules onto the substrates. The Smurf1-Ub interaction is required for Smurf1 catalytic ligase activity to promote substrate degradation. However, so far specific regulators or compounds controlling Smurf1-Ub interaction and the ligase activity have not been identified...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28870989/a-stepwise-model-of-reaction-diffusion-and-positional-information-governs-self-organized-human-peri-gastrulation-like-patterning
#10
Mukul Tewary, Joel Ostblom, Laura Prochazka, Teresa Zulueta-Coarasa, Nika Shakiba, Rodrigo Fernandez-Gonzalez, Peter W Zandstra
How position-dependent cell fate acquisition occurs during embryogenesis is a central question in developmental biology. To study this process, we developed a defined, high-throughput assay to induce peri-gastrulation-associated patterning in geometrically-confined human pluripotent stem cell (hPSC) colonies. We observed that, upon BMP4 treatment, phosphorylated SMAD1 (pSMAD1) activity in the colonies organized into a radial gradient. We developed a Reaction-Diffusion (RD) based computational model and observed that the self-organization of pSMAD1 signaling was consistent with the RD principle...
September 4, 2017: Development
https://www.readbyqxmd.com/read/28852126/decrease-of-fstl1-bmp4-smad-signaling-predicts-poor-prognosis-in-lung-adenocarcinoma-but-not-in-squamous-cell-carcinoma
#11
Jean Chiou, Chia-Yi Su, Yi-Hua Jan, Chih-Jen Yang, Ming-Shyan Huang, Yung-Luen Yu, Michael Hsiao
Follistatin-related protein 1 (FSTL1) plays a critical role in lung development through regulating BMP4-p-Smad1/5/8-Smad4 pathway. Regarding that many developmental pathways in embryogenesis are dysregulated in cancer, we aim to unravel the role of FSTL1-BMP4-Smad pathway in lung cancer. Our results showed low FSTL1 immunoexpression was significantly correlated with poor prognosis while patients with low BMP4 or low Smad4 immunoexpression showed a trend toward poor prognosis. When stratified by different histological types, low FSTL1, BMP4, and Smad4 expression retained their trends in predicting poor prognosis in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma (SCC)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842696/adhesion-to-stromal-cells-mediates-imatinib-resistance-in-chronic-myeloid-leukemia-through-erk-and-bmp-signaling-pathways
#12
Atul Kumar, Jina Bhattacharyya, Bithiah Grace Jaganathan
Chronic myeloid leukemia (CML) is characterized by abnormal proliferation of myeloid cells which when untreated leads to bone marrow failure. Imatinib mesylate (IM) is the first line of therapy for treatment of CML and results in remission in most cases. However, a significant percentage of patients develop chemoresistance to IM, which might be due to the presence of chemoresistant cells in the bone marrow. In the current study, we explored the role of cell-cell interaction of CML cells with the bone marrow stromal cells in the development of chemoresistance in CML...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28838258/the-protective-effects-of-bone-morphogenetic-protein-7-against-epithelial-injury-and-matrix-metalloproteases-upregulation-induced-by-silica-in-vitro
#13
D Liang, G An, Z Zhu, Y Wang, G Yang, X Li, P Niu, L Chen, L Tian
OBJECTIVE: We investigate the effects of bone morphogenetic protein-7 (BMP-7) on models with silica-induced and macrophage-mediated fibrosis and its possible mechanisms in vitro. METHODS: Rat alveolar II epithelial (RLE-6TN) cells were incubated with the supernatant of mouse macrophage-like cells (RAW264.7) and treated with 0, 25, 50, and 100 μg/mL silica. Using Western blotting, the epithelial markers (surfactant proteins-C and E-cadherin) and the mesenchymal markers (fibronectin (FN) and viminten (Vim)) were detected...
September 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28829997/msx2-is-required-for-vascular-smooth-muscle-cells-osteoblastic-differentiation-but-not-calcification-in-insulin-resistant-ob-ob-mice
#14
Maria Claudina Andrade, Luciana S Carmo, Elisangela Farias-Silva, Marcel Liberman
BACKGROUND AND AIMS: Obesity and diabetes potentiate vascular calcification by increasing vascular smooth muscle cells osteoblastic differentiation mediated by the transcription factor Msx2 and bone morphogenetic protein-2 signaling. However, Bmp-2/Msx2 crosstalk to induce VSMC osteogenic phenotype transition and calcification is poorly understood in diabetes. We aimed to investigate mechanisms underlying Bmp-2-driven VSMC osteogenic differentiation and calcification in leptin-deficient ob/ob mice...
July 29, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28821740/irs4-a-novel-modulator-of-bmp-smad-and-akt-signalling-during-early-muscle-differentiation
#15
Gina Dörpholz, Arunima Murgai, Jerome Jatzlau, Daniel Horbelt, Mohammad Poorgholi Belverdi, Christina Heroven, Isabelle Schreiber, Gisela Wendel, Karen Ruschke, Sigmar Stricker, Petra Knaus
Elaborate regulatory networks of the Bone Morphogenetic Protein (BMP) pathways ensure precise signalling outcome during cell differentiation and tissue homeostasis. Here, we identified IRS4 as a novel regulator of BMP signal transduction and provide molecular insights how it integrates into the signalling pathway. We found that IRS4 interacts with the BMP receptor BMPRII and specifically targets Smad1 for proteasomal degradation consequently leading to repressed BMP/Smad signalling in C2C12 myoblasts while concomitantly activating the PI3K/Akt axis...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815657/celecoxib-inhibits-osteoblast-differentiation-independent-of-cyclooxygenase-activity
#16
Atsushi Matsuyama, Sen Higashi, Saori Tanizaki, Takahiko Morotomi, Ayako Washio, Tomoko Ohsumi, Chiaki Kitamura, Hiroshi Takeuchi
Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects primarily by inhibiting the activity of cyclooxygenase (COX), thus suppressing prostaglandin synthesis. Some NSAIDs are known to perform functions other than pain control, such as suppressing tumour cell growth, independent of their COX-inhibiting activity. To identify NSAIDs with COX-independent activity, we examined various NSAIDs for their ability to inhibit osteoblastic differentiation using the mouse pre-osteoblast cell line MC3T3-E1. Only celecoxib and valdecoxib strongly inhibited osteoblastic differentiation, and this effect was not correlated with COX-inhibiting activity...
August 16, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28814721/acceleration-of-osteoblast-differentiation-by-a-novel-osteogenic-compound-dmp-pyt-through-activation-of-both-the-bmp-and-wnt-pathways
#17
Su Jung Bae, Hye Joo Kim, Hee Yeon Won, Yong Ki Min, Eun Sook Hwang
Osteoblast differentiation is regulated through the successive activation of signaling molecules by a complex interplay of extracellular signals such as bone morphogenetic protein (BMP) and Wnt ligands. Numerous studies have identified natural as well as synthetic compounds with osteogenic activity through the regulation of either BMP/SMADs or the Wnt/β-catenin pathway. Here, we attempted to isolate small molecules that concurrently activated both SMADs and β-catenin, which led to the discovery of a novel potent osteogenic compound, DMP-PYT...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814648/zc4h2-stabilizes-smads-to-enhance-bmp-signalling-which-is-involved-in-neural-development-in-xenopus
#18
Pengcheng Ma, Biyu Ren, Xiangcai Yang, Bin Sun, Xiaoliang Liu, Qinghua Kong, Chaocui Li, Bingyu Mao
Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance, differentiation and embryonic development. Intracellularly, BMP signalling is mediated by Smad proteins, which are regulated post-transcriptionally through reversible phosphorylation and ubiquitination. ZC4H2 is a small nuclear protein associated with intellectual disability and neural development in humans. Here, we report that ZC4H2 is highly expressed in the developing neural system and is involved in neural patterning and BMP signalling in Xenopus Knockdown of ZC4H2 led to expansion of the expression of the pan neural plate marker Sox2 in Xenopus embryos...
August 2017: Open Biology
https://www.readbyqxmd.com/read/28812969/functional-expression-of-bmp7-receptors-in-oral-epithelial-cells-interleukin-17f-production-in-response-to-bmp7
#19
Kensuke Nishio, Yasumasa Ozawa, Hisanori Ito, Takashi Kifune, Tatsuya Narita, Toshimitsu Iinuma, Nobuhito Gionhaku, Masatake Asano
BACKGROUND: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily. Recently, BMP7 has been demonstrated to be produced by salivary glands and contribute to embryonic branching in mice. The BMP7 in saliva is thought to be delivered to the oral cavity and is expected to contact with stratified squamous epithelial cells which line the surface of oral mucosa. In this study, we attempted to investigate the effects of BMP7 on oral epithelial cells...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28809431/transdifferentiation-of-myoblasts-into-osteoblasts-possible-use-for-bone-therapy
#20
REVIEW
Daphne P L Lin, Revathy Carnagarin, Arun Dharmarajan, Crispin R Dass
OBJECTIVES: Transdifferentiation is defined as the conversion of one cell type to another and is an ever-expanding field with a growing number of cells found to be capable of such a process. To date, the fact remains that there are limited treatment options for fracture healing, osteoporosis and bone repair post-destruction by bone tumours. Hence, this review focuses on the transdifferentiation of myoblast to osteoblast as a means to further understand the transdifferentiation process and to investigate a potential therapeutic option if successful...
August 15, 2017: Journal of Pharmacy and Pharmacology
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