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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/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
#2
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
#3
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
#4
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
#5
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/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
#6
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
#7
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/28219352/retinoic-acid-promotes-expression-of-germline-specific-genes-in-chicken-blastoderm-cells-by-stimulating-smad1-5-phosphorylation-in-a-feeder-free-culture-system
#8
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
#9
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
#10
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
#11
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/28155178/tumor-necrosis-factor-%C3%AE-and-transforming-growth-factor-%C3%AE-1-facilitate-differentiation-and-proliferation-of-tendon-derived-stem-cells-in-vitro
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28128224/pyrintegrin-induces-soft-tissue-formation-by-transplanted-or-endogenous-cells
#15
Bhranti S Shah, Mo Chen, Takahiro Suzuki, Mildred Embree, Kimi Kong, Chang H Lee, Ling He, Lusai Xiang, Jeffrey A Ahn, Sheng Ding, Jeremy J Mao
Focal adipose deficiency, such as lipoatrophy, lumpectomy or facial trauma, is a formidable challenge in reconstructive medicine, and yet scarcely investigated in experimental studies. Here, we report that Pyrintegrin (Ptn), a 2,4-disubstituted pyrimidine known to promote embryonic stem cells survival, is robustly adipogenic and induces postnatal adipose tissue formation in vivo of transplanted adipose stem/progenitor cells (ASCs) and recruited endogenous cells. In vitro, Ptn stimulated human adipose tissue derived ASCs to differentiate into lipid-laden adipocytes by upregulating peroxisome proliferator-activated receptor (PPARγ) and CCAAT/enhancer-binding protein-α (C/EBPα), with differentiated cells increasingly secreting adiponectin, leptin, glycerol and total triglycerides...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28114883/release-of-endothelial-cell-associated-vegfr2-during-tgf-%C3%AE-modulated-angiogenesis-in-vitro
#16
M Jarad, E A Kuczynski, J Morrison, A M Viloria-Petit, B L Coomber
BACKGROUND: Sprouting angiogenesis requires vascular endothelial proliferation, migration and morphogenesis. The process is regulated by soluble factors, principally vascular endothelial growth factor (VEGF), and via bidirectional signaling through the Jagged/Notch system, leading to assignment of tip cell and stalk cell identity. The cytokine transforming growth factor beta (TGF-β) can either stimulate or inhibit angiogenesis via its differential surface receptor signaling. Here we evaluate changes in expression of angiogenic signaling receptors when bovine aortic endothelial cells were exposed to TGF-β1 under low serum conditions...
January 23, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28103025/identification-of-the-first-selective-activin-receptor-like-kinase-1-inhibitor-a-reversible-version-of-l-783277
#17
Hanna Cho, Sandip Sengupta, Sean S H Jeon, Wooyoung Hur, Hwan Geun Choi, Hong-Seog Seo, Byung Joo Lee, Jeong Hun Kim, Minhwan Chung, Noo Li Jeon, Nam Doo Kim, Taebo Sim
We synthesized 1 (San78-130), a reversible version of L-783277, as a selective and potent ALK1 inhibitor. Our study showed that 1 possesses great kinase selectivity against a panel of 342 kinases and more potent activity against ALK1 than L-783277. Among the six ALK isotypes (ALK1-6), ALK1 is most significantly inhibited by compound 1. Compound 1 suppresses the BMP9-induced Smad1/5 pathway by mainly inhibiting ALK1 in C2C12 cells. Our molecular dynamics simulations suggest that H-bonding interaction between the C-4' hydroxyl group of 1 and Arg334 of ALK1 substantially contributes to the ALK1 inhibition...
February 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28067796/combined-effects-of-androgen-and-growth-hormone-on-osteoblast-marker-expression-in-mouse-c2c12-and-mc3t3-e1-cells-induced-by-bone-morphogenetic-protein
#18
Kosuke Kimura, Tomohiro Terasaka, Nahoko Iwata, Takayuki Katsuyama, Motoshi Komatsubara, Ryota Nagao, Kenichi Inagaki, Fumio Otsuka
Osteoblasts undergo differentiation in response to various factors, including growth factors and steroids. Bone mass is diminished in androgen- and/or growth hormone (GH)-deficient patients. However the functional relationship between androgen and GH, and their combined effects on bone metabolism, remains unclear. Here we investigated the mutual effects of androgen and GH on osteoblastic marker expression using mouse myoblastic C2C12 and osteoblast-like MC3T3-E1 cells. Combined treatment with dihydrotestosterone (DHT) and GH enhanced BMP-2-induced expression of Runx2, ALP, and osteocalcin mRNA, compared with the individual treatments in C2C12 cells...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28063228/trim33-is-essential-for-osteoblast-proliferation-and-differentiation-via-bmp-pathway
#19
Jia Guo, Wei Qin, Quan Xing, Manman Gao, Fuxin Wei, Zhi Song, Lingling Chen, Ying Lin, Xianling Gao, Zhengmei Lin
Tripartite motif containing 33 (TRIM33) functions both as a positive and negative regulator of the TGF-β/BMP pathway in tumors; however, its effect and mechanism during osteoblast proliferation and differentiation, which involves the TGF-β/BMP pathway is not defined. In this study, we used mouse C3H10T1/2 mesenchymal stem cell line and MC3T3-E1 preosteoblasts to investigate the role of TRIM33 during this process. The results demonstrated that the expression of TRIM33 increased during the differentiation. Moreover, the overexpression or knockdown of TRIM33 resulted in both an augmentation or decrease in osteoblast differentiation, which were measured by the expression of alkaline phosphatase (ALP) at the mRNA level, both Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) at the protein level, and the formation of mineral modules...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28035402/transforming-growth-factor-%C3%AE-1-suppresses-bone-morphogenetic-protein-2-induced-mesenchymal-epithelial-transition-in-hsc-4-human-oral-squamous-cell-carcinoma-cells-via-smad1-5-9-pathway-suppression
#20
Takahiro Chiba, Akira Ishisaki, Seiko Kyakumoto, Toshiyuki Shibata, Hiroyuki Yamada, Masaharu Kamo
Squamous cell carcinoma is the most common cancer in the oral cavity. We previously demonstrated that transforming growth factor-β1 (TGF-β1) promotes the epithelial-mesenchymal transition (EMT) of human oral squamous cell carcinoma (hOSCC) cells; however, it remains to be clarified whether the TGF-β superfamily member bone morphogenetic protein (BMP) affects this process in hOSCC cells. Here, we examined the independent and collective effects of TGF-β1 and BMP-2 on EMT and mesenchymal‑epithelial transition (MET) in a panel of four hOSCC cell lines...
February 2017: Oncology Reports
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