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https://www.readbyqxmd.com/read/28327634/scleraxis-is-required-for-maturation-of-tissue-domains-for-proper-integration-of-the-musculoskeletal-system
#1
Yuki Yoshimoto, Aki Takimoto, Hitomi Watanabe, Yuji Hiraki, Gen Kondoh, Chisa Shukunami
Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is expressed persistently in tendons/ligaments, but transiently in entheseal cartilage. In this study, we generated a novel Scx(Cre) knock-in (KI) allele, by in-frame replacement of most of Scx exon 1 with Cre recombinase (Cre), to drive Cre expression using Scx promoter and to inactivate the endogenous Scx. Reflecting the intensity and duration of endogenous expression, Cre-mediated excision occurs in tendinous and ligamentous tissues persistently expressing Scx...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322449/tgf-%C3%AE-inhibits-osteogenesis-by-upregulating-the-expression-of-ubiquitin-ligase-smurf1-via-mapk-erk-signaling
#2
Xuewu Sun, Ziang Xie, Yan Ma, Xin Pan, Jiying Wang, Zhijun Chen, Peihua Shi
High incidence of osteoporotic fractures emphasizes the necessity of developing effective measures to promote osteogenesis. In our study, we investigated a possible role of MAPK-ERK signaling in the TGF-β-mediated osteoblastic differentiation. Our results indicated that TGF-β activated the MAPK-ERK pathway and inhibited osteogenesis in mesenchymal pluripotent cell line, C3H10T1/2, and preosteoblastic cell line, MC3T3 cells. And the downregulation of MAPK-ERK signaling using pharmacological inhibitor U0126 and RNA interference rescued osteoblast differentiation suppressed by TGF-β, which was confirmed by Alkaline phosphatase (ALP) staining and alizarrn red staining and the enhanced expression of osteogenesic markers...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28299652/roles-of-runx2-in-skeletal-development
#3
Toshihisa Komori
Runx2 is the most upstream transcription factor essential for osteoblast differentiation. It regulates the expression of Sp7, the protein of which is a crucial transcription factor for osteoblast differentiation, as well as that of bone matrix genes including Spp1, Ibsp, and Bglap2. Runx2 is also required for chondrocyte maturation, and Runx3 has a redundant function with Runx2 in chondrocyte maturation. Runx2 regulates the expression of Col10a1, Spp1, Ibsp, and Mmp13 in chondrocytes. It also inhibits chondrocytes from acquiring the phenotypes of permanent cartilage chondrocytes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28298490/aberrant-caveolin-1-mediated-smad-signaling-and-proliferation-identified-by-analysis-of-adenine-474-deletion-mutation-c-474dela-in-patient-fibroblasts-a-new-perspective-in-the-mechanism-of-pulmonary-hypertension
#4
Glenn Marsboom, Zhenlong Chen, Yang Yuan, Yanmin Zhang, Chinnaswamy Tiruppathi, James E Loyd, Eric D Austin, Roberto F Machado, Richard D Minshall, Jalees Rehman, Asrar B Malik
A heterozygous Caveolin-1 c.474delA mutation has been identified in a family with heritable pulmonary arterial hypertension (PAH). This frameshift mutation leads to caveolin-1 protein that contains all known functional domains but has a change only in the final 20 amino acids of the C terminus. Here we studied how this mutation alters caveolin-1 function using patient-derived fibroblasts. Transmission electron microscopy showed that fibroblasts carrying the c.474delA mutation formed typical caveolae. Expression of mutated caveolin-1 in caveolin-1-null mouse fibroblasts failed to induce formation of caveolae due to retention of the mutated protein in the endoplasmic reticulum...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28298362/negative-regulation-of-smad1-pathway-and-collagen-iv-expression-by-store-operated-ca2-entry-in-glomerular-mesangial-cells
#5
Peiwen Wu, Yuezhong Ren, Yuhong Ma, Yanxia Wang, Hui Jiang, Sarika Chaudhari, Mark E Davis, Jonathan E Zuckerman, Rong Ma
Collagen IV (Col IV) is a major component of expanded glomerular extracellular matrix in diabetic nephropathy and Smad1 is a key molecule regulating Col IV expression in mesangial cells (MCs). The present study was conducted to determine if Smad1 pathway and Col IV protein abundance were regulated by store-operated Ca2+ entry (SOCE). In cultured human MCs, pharmacological inhibition of SOCE significantly increased the total amount of Smad1 protein. Activation of SOCE blunted high glucose-increased Smad1 protein content...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28288971/activation-of-cd137-signaling-promotes-angiogenesis-in-atherosclerosis-via-modulating-endothelial-smad1-5-nfatc1-pathway
#6
Jiayi Weng, Cuiping Wang, Wei Zhong, Bo Li, Zhongqun Wang, Chen Shao, Yao Chen, Jinchuan Yan
BACKGROUND: Excessive angiogenesis is a key feature of vulnerable atherosclerotic plaques, and is considered an independent predictor of cardiovascular risk. CD137 signaling has previously been shown to be involved in atherosclerosis. However, the possible role of CD137 signaling in regulating angiogenesis has not been reported. METHODS AND RESULTS: Apolipoprotein E-deficient (ApoE(-/-)) mice were used as the in vivo model of atherosclerosis. Masson and immunohistochemical analysis of atherosclerotic plaques and Matrigel plug assay were used to evaluate the angiogenesis...
March 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28259395/short-communication-tryptic-%C3%AE-casein-hydrolysate-modulates-enteric-nervous-system-development-in-primary-culture
#7
F Cossais, I Clawin-Rädecker, P C Lorenzen, M Klempt
The intestinal tract of the newborn is particularly sensitive to gastrointestinal disorders, such as infantile diarrhea or necrotizing colitis. Perinatal development of the gut also encompasses the maturation of the enteric nervous system (ENS), a main regulator of intestinal motility and barrier functions. It was recently shown that ENS maturation can be enhanced by nutritional factors to improve intestinal maturation. Bioactivity of milk proteins is often latent, requiring the release of bioactive peptides from inactive native proteins...
March 2, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28250237/bovine-embryo-oviduct-interaction-in-vitro-reveals-an-early-crosstalk-mediated-by-bmp-signaling
#8
Elina Vanesa García, Meriem Hamdi, Antonio Daniel Barrera, Maria-Jesús Sánchez Calabuig, Alfonso Gutierrez-Adan, Dimitrios Rizos
Signaling components of Bone Morphogenetic Proteins (BMPs) are expressed in an anatomically and temporally regulated fashion in bovine oviduct. However, a local response of this signaling to the presence of the embryo has yet to be elucidated. The aim of the present study was to evaluate if early embryo-oviduct interaction induces changes in the gene expression of BMP signaling components. For this purpose, we used an in vitro co-culture system to investigate the local interaction between bovine oviductal epithelial cells (BOEC) from the isthmus region with early embryos during two developmental periods: before (from the 2-cell to 8-cell stage) or during (from the 8-cell to 16-cell stage) the main phase of embryonic genome activation (EGA)...
March 1, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28245560/the-regulations-of-deubiquitinase-usp15-and-its-pathophysiological-mechanisms-in-diseases
#9
REVIEW
Chon-Kit Chou, Yu-Ting Chang, Michal Korinek, Yei-Tsung Chen, Ya-Ting Yang, Steve Leu, I-Ling Lin, Chin-Ju Tang, Chien-Chih Chiu
Deubiquitinases (DUBs) play a critical role in ubiquitin-directed signaling by catalytically removing the ubiquitin from substrate proteins. Ubiquitin-specific protease 15 (USP15), a member of the largest subfamily of cysteine protease DUBs, contains two conservative cysteine (Cys) and histidine (His) boxes. USP15 harbors two zinc-binding motifs that are essential for recognition of poly-ubiquitin chains. USP15 is grouped into the same category with USP4 and USP11 due to high degree of homology in an N-terminal region consisting of domains present in ubiquitin-specific proteases (DUSP) domain and ubiquitin-like (UBL) domain...
February 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28240243/smad3-and-smad4-have-a-more-dominant-role-than-smad2-in-tgf%C3%AE-induced-chondrogenic-differentiation-of-bone-marrow-derived-mesenchymal-stem-cells
#10
Laurie M G de Kroon, Roberto Narcisi, Guus G H van den Akker, Elly L Vitters, Esmeralda N Blaney Davidson, Gerjo J V M van Osch, Peter M van der Kraan
To improve cartilage formation by bone marrow-derived mesenchymal stem cells (BMSCs), the signaling mechanism governing chondrogenic differentiation requires better understanding. We previously showed that the transforming growth factor-β (TGFβ) receptor ALK5 is crucial for chondrogenesis induced by TGFβ. ALK5 phosphorylates SMAD2 and SMAD3 proteins, which then form complexes with SMAD4 to regulate gene transcription. By modulating the expression of SMAD2, SMAD3 and SMAD4 in human BMSCs, we investigated their role in TGFβ-induced chondrogenesis...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28235949/bmp4-inhibits-pdgf-induced-proliferation-and-collagen-synthesis-via-pka-mediated-inhibition-of-calpain-2-in-pulmonary-artery-smooth-muscle-cells
#11
PengCheng Cai, Laszlo Kovacs, Sam Dong, Guangyu Wu, Yunchao Su
In the present study, we investigated the effect of bone morphogenetic protein 4 (BMP4) on PDGF-induced proliferation and collagen synthesis in PASMCs. Normal human PASMCs were incubated with and without PDGF-BB in the absence and presence of BMP4 for 0.5 to 24 h. Then the protein levels of collagen-I, p-Smad2/3, p-Smad1/5, and intracellular active TGFβ1, calpain activity and cell proliferation were measured. The results showed that BMP4 induced an increase in p-Smad1/5 but had no effect on the protein levels of collagen-I, p-Smad2/3, and intracellular active TGFβ1, and calpain activity in PASMCs...
February 24, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28219948/genomic-integration-of-wnt-%C3%AE-catenin-and-bmp-smad1-signaling-coordinates-foregut-and-hindgut-transcriptional-program
#12
Mariana L Stevens, Praneet Chaturvedi, Scott A Rankin, Melissa Macdonald, Sajjeev Jagannathan, Masashi Yukawa, Artem Barski, Aaron M Zorn
Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are integrated in the genome is poorly understood. Here we identified the transcriptomes of Xenopus foregut and hindgut progenitors, which are conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/β-catenin acts as a genome-wide toggle between foregut and hindgut programs...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28219352/retinoic-acid-promotes-expression-of-germline-specific-genes-in-chicken-blastoderm-cells-by-stimulating-smad1-5-phosphorylation-in-a-feeder-free-culture-system
#13
Xiaochuan Tang, Shiyong Xu, Hongpeng Zhang, Qing Chen, Rongyang Li, Wangjun Wu, Minli Yu, Honglin Liu
BACKGROUND: Producing transgenic chickens with chicken blastodermal cells (cBCs) is inefficient due to the extremely low germline transmission capacity of cBCs. As chicken primordial germ cells (PGCs) have been reported as an efficient method for producing transgenic chickens, the inefficiency of cBCs could potentially be resolved by inducing them to differentiate into germ cells. However, whether chemical inducers are able to enhance cBCs germline competence in vitro is unknown and the molecular mechanisms of differentiation of chicken pluripotent cells into germ cells are poorly understood...
February 20, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28213129/cyclic-compressive-stress-induced-scinderin-regulates-progress-of-developmental-dysplasia-of-the-hip
#14
Cheng-Long Wang, Hui Wang, Fei Xiao, Chuan-Dong Wang, Guo-Li Hu, Jun-Feng Zhu, Chao Shen, Bin Zuo, Yi-Min Cui, De Li, Yuan-Gao, Xiao-Ling Zhang, Xiao-Dong Chen
Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by a mismatch between acetabulum and femoral head. Mechanical force plays an important role during the occurrence and development of abnormities in acetabulum and femoral head. In this study, we established a mechanical force model named cyclic compressive stress (Ccs). To analyze the effect of Ccs on DDH, we detected special genes in chondrocytes and osteoblasts. Results showed that Ccs downregulated chondrogenesis of ADTC5 in a concentration-dependent manner...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28202082/bone-morphogenetic-proteins-and-myostatin-pathways-key-mediator-of-human-sarcopenia
#15
Manuel Scimeca, Eleonora Piccirilli, Francesca Mastrangeli, Cecilia Rao, Maurizio Feola, Augusto Orlandi, Elena Gasbarra, Elena Bonanno, Umberto Tarantino
BACKGROUND: Sarcopenia, osteoporosis and osteoarthritis are the most frequent musculoskeletal disorders affecting older people. The main aim of this study was to test the hypothesis that the balance between BMPs and myostatin pathways regulates the age-related muscle degeneration in OP and OA patients. To this end, we investigated the relationship among the expression of BMP-2/4-7, myostatin and phosphorylated Smads1-5-8 and the muscle quality, evaluated in term of fibers atrophy and satellite cells activity...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28199984/autocrine-and-paracrine-stip1-signaling-promote-osteolytic-bone-metastasis-in-renal-cell-carcinoma
#16
Jiang Wang, Hongbo You, Jun Qi, Caihong Yang, Ye Ren, Hao Cheng
Bone metastases are responsible for some of the most devastating complications of renal cell carcinoma (RCC). However, pro-metastatic factors leading to the highly osteolytic characteristics of RCC bone metastasis have barely been explored. We previously developed novel bone-seeking RCC cell lines by the in vivo selection strategy and performed a comparative proteome analysis on their total cell lysate. Here, we focused on STIP1 (stress-induced phosphoprotein 1), the high up-regulated protein in the bone-seeking cells, and explored its clinical relevance and functions in RCC bone metastasis...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28167128/testosterone-promotes-tube-formation-of-endothelial-cells-isolated-from-veins-via-activation-of-smad1-protein
#17
Pei Liu, Xiaosa Li, Fuhu Song, Ping Li, Jinzhi Wei, Qing Yan, Xingyan Xu, Jun Yang, Chuanxiang Li, Xiaodong Fu
Testosterone (T) deficiency is positively correlated with the increased incidence of cardiovascular disease. However, the effects of T on vascular endothelial cells remain obscure. Tube formation capacity is critical for vascular regeneration/repair and Smad1 plays an important role in these events. In this study, we investigated the effects of T on Smad1 activation and tube formation of cultured human umbilical endothelial cells (HUVECs). Our results showed that T rapidly increased endothelial Smad1 phosphorylation...
May 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28155178/tumor-necrosis-factor-%C3%AE-and-transforming-growth-factor-%C3%AE-1-facilitate-differentiation-and-proliferation-of-tendon-derived-stem-cells-in-vitro
#18
Peilin Han, Qingbo Cui, Shulong Yang, Hao Wang, Peng Gao, Zhaozhu Li
OBJECTIVES: To investigate the effects of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) on the proliferation and differentiation of tendon-derived stem cells (TDSC). RESULTS: TNF-α inhibits the proliferation and tenogenic/osteogenic differentiation of TDSC but, after simultaneous or sequential treatment with TGF-β1 and TNF-α, the expression of tenogenic/osteogenic-related marker and proliferation of TDSC was significantly increased...
February 2, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28134270/signal-mingle-micropatterns-of-bmp-2-and-fibronectin-on-soft-biopolymeric-films-regulate-myoblast-shape-and-smad-signaling
#19
Vincent Fitzpatrick, Laure Fourel, Olivier Destaing, Flora Gilde, Corinne Albigès-Rizo, Catherine Picart, Thomas Boudou
In vivo, bone morphogenetic protein 2 (BMP-2) exists both in solution and bound to the extracellular matrix (ECM). While these two modes of presentation are known to influence cell behavior distinctly, their role in the niche microenvironment and their functional relevance in the genesis of a biological response has sparsely been investigated at a cellular level. Here we used the natural affinity of BMP-2 for fibronectin (FN) to engineer cell-sized micropatterns of BMP-2. This technique allowed the simultaneous control of the spatial presentation of fibronectin-bound BMP-2 and cell spreading...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28128304/targeting-osteoblastic-casein-kinase-2-interacting-protein-1-to-enhance-smad-dependent-bmp-signaling-and-reverse-bone-formation-reduction-in-glucocorticoid-induced-osteoporosis
#20
Jin Liu, Changwei Lu, Xiaohao Wu, Zongkang Zhang, Jie Li, Baosheng Guo, Defang Li, Chao Liang, Lei Dang, Xiaohua Pan, Songlin Peng, Aiping Lu, Baoting Zhang, Ge Zhang
The underlying mechanism of the reduced bone formation during the development of glucocorticoid-induced osteoporosis (GIO) remains unclear. Here, we found that the highly expressed CKIP-1 together with lowly expressed total and phosphorylated Smad1/5 in bone samples was accompanied by either the reduced serum bone formation markers in GIO patients or the decreased bone formation in GIO mice. In vitro studies showed that the highly expressed CKIP-1 could promote Smad1 ubiquitination to suppress the Smad-dependent BMP signaling and inhibit osteogenic differentiation and mineral deposition in MC3T3-E1 cells during glucocorticoid treatment...
January 27, 2017: Scientific Reports
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