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Ali Borazjani, Nathan Kow, Samantha Harris, Beri Ridgeway, Margot S Damaser
OBJECTIVE: The aim of this study was to compare differences in expressions and relationships between key genes involved in extracellular matrix metabolism and tissue cellularity in women with and without pelvic organ prolapse (POP). METHODS: A total of 80 biopsies (anterior cuff, posterior cuff, and/or leading edge) were obtained from 30 women: n = 10 premenopausal without POP (controls), n = 10 premenopausal with POP, and n = 10 postmenopausal with POP. Quantitative reverse-transcriptase polymerase chain reaction was used to assess gene expression of bone morphogenetic protein 1 (BMP1), collagen types I (COL1) and III (COL3), relaxin family peptide receptor 1 (RXFP1), matrix metallopeptidase 2, and TIMP metallopeptidase inhibitors 2 and 3...
September 15, 2016: Female Pelvic Medicine & Reconstructive Surgery
Rebecca C Pollitt, Vrinda Saraff, Ann Dalton, Emma A Webb, Nick J Shaw, Glenda J Sobey, M Zulf Mughal, Emma Hobson, Farhan Ali, Nicholas J Bishop, Paul Arundel, Wolfgang Högler, Meena Balasubramanian
Osteogenesis Imperfecta (OI) is an inherited bone fragility disorder most commonly associated with autosomal dominant mutations in the type I collagen genes. Autosomal recessive mutations in a number of genes have also been described, including the BMP1 gene that encodes the mammalian Tolloid (mTLD) and its shorter isoform bone morphogenic protein-1 (BMP1). To date, less than 20 individuals with OI have been identified with BMP1 mutations, with skeletal phenotypes ranging from mild to severe and progressively deforming...
August 30, 2016: American Journal of Medical Genetics. Part A
Clint L Miller, Milos Pjanic, Ting Wang, Trieu Nguyen, Ariella Cohain, Jonathan D Lee, Ljubica Perisic, Ulf Hedin, Ramendra K Kundu, Deshna Majmudar, Juyong B Kim, Oliver Wang, Christer Betsholtz, Arno Ruusalepp, Oscar Franzén, Themistocles L Assimes, Stephen B Montgomery, Eric E Schadt, Johan L M Björkegren, Thomas Quertermous
Coronary artery disease (CAD) is the leading cause of mortality and morbidity, driven by both genetic and environmental risk factors. Meta-analyses of genome-wide association studies have identified >150 loci associated with CAD and myocardial infarction susceptibility in humans. A majority of these variants reside in non-coding regions and are co-inherited with hundreds of candidate regulatory variants, presenting a challenge to elucidate their functions. Herein, we use integrative genomic, epigenomic and transcriptomic profiling of perturbed human coronary artery smooth muscle cells and tissues to begin to identify causal regulatory variation and mechanisms responsible for CAD associations...
July 8, 2016: Nature Communications
Marike M van Beuge, Evert-Jan P M Ten Dam, Paul M N Werker, Ruud A Bank
BACKGROUND: Dupuytren's disease is a fibroproliferative disease of the hand and fingers, which usually manifests as two different phenotypes within the same patient. The disease first causes a nodule in the palm of the hand, while later, a cord develops, causing contracture of the fingers. RESULTS: We set out to characterize the two phenotypes by comparing matched cord and nodule tissue from ten Dupuytren's patients. We found that nodule tissue contained more proliferating cells, CD68-positive macrophages and α-smooth muscle actin (α-SMA)-positive myofibroblastic cells...
2016: Fibrogenesis & Tissue Repair
Alison M Muir, Dawiyat Massoudi, Ngon Nguyen, Douglas R Keene, Se-Jin Lee, David E Birk, Jeffrey M Davidson, M Peter Marinkovich, Daniel S Greenspan
Closely related extracellular metalloproteinases bone morphogenetic protein 1 (BMP1) and mammalian Tolloid-like 1 (mTLL1) are co-expressed in various tissues and have been suggested to have overlapping roles in the biosynthetic processing of extracellular matrix components. Early lethality of mice null for the BMP1 gene Bmp1 or the mTLL1 gene Tll1 has impaired in vivo studies of these proteinases. To overcome issues of early lethality and functional redundancy we developed the novel BT(KO) mouse strain, with floxed Bmp1 and Tll1 alleles, for induction of postnatal, simultaneous ablation of the two genes...
June 27, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Hongmei Gu, Amanda J Fisher, Elizabeth A Mickler, Frank Duerson, Oscar W Cummings, Marc Peters-Golden, Homer L Twigg, Trent M Woodruff, David S Wilkes, Ragini Vittal
Complement activation, an integral arm of innate immunity, may be the critical link to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Whereas we have previously reported elevated anaphylatoxins-complement component 3a (C3a) and complement component 5a (C5a)-in IPF, which interact with TGF-β and augment epithelial injury in vitro, their role in IPF pathogenesis remains unclear. The objective of the current study is to determine the mechanistic role of the binding of C3a/C5a to their respective receptors (C3aR and C5aR) in the progression of lung fibrosis...
June 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
H J Wright, J Arulmoli, M Motazedi, L J Nelson, F S Heinemann, L A Flanagan, O V Razorenova
Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic form of breast cancer that lacks the estrogen, progesterone and HER2 receptors and is resistant to targeted and hormone therapies. TNBCs express high levels of the transmembrane glycoprotein, complement C1r/C1s, Uegf, Bmp1 (CUB)-domain containing protein 1 (CDCP1), which has been correlated with the aggressiveness and poor prognosis of multiple carcinomas. Full-length CDCP1 (flCDCP1) can be proteolytically cleaved, resulting in a cleaved membrane-bound isoform (cCDCP1)...
September 8, 2016: Oncogene
Chengyue Zhang, Limin Shu, Hyuck Kim, Tin Oo Khor, Renyi Wu, Wenji Li, Ah-Ng Tony Kong
SCOPE: Tumor metastasis greatly contributes to the mortality of prostate cancer. The glucosinolate-derived phenethyl isothiocyanate (PEITC) has been widely documented to reduce the risk of prostate cancer by modulating multiple biologically relevant processes. Emerging evidence suggests that PEITC may exert its anti-cancer effects through epigenetic mechanisms including microRNAs. Altered levels of miRNA have been linked to tumor malignancy due to their capacity to regulate functional gene expression in carcinogenesis...
June 2016: Molecular Nutrition & Food Research
Xiaocan Lei, Kuiqing Cui, Zhipeng Li, Jie Su, Jianrong Jiang, Haihang Zhang, Qingyou Liu, Deshun Shi
BMP1/TLD-related metalloproteinases play a key role in morphogenesis via the proteolytic maturation of a number of extracellular matrix proteins and the activation of a subset of growth factors of the transforming growth factor beta superfamily. Recent data indicated that BMP1 is expressed in sheep ovarian follicles and showed a protease activity. The aim of the present study was to characterize the function of the buffalo BMP1 gene in folliculogenesis. A 3195-bp buffalo BMP1 mRNA fragment was firstly cloned and sequenced, which contained a whole 2967-bp codon sequence...
March 15, 2016: Theriogenology
Hala Kufaishi, May Alarab, Harold Drutz, Stephen Lye, Oksana Shynlova
BACKGROUND: This study tested a hypothesis that primary human vaginal cells derived from tissue of premenopausal women with severe pelvic organ prolapse (POP-HVCs) would display differential functional characteristics as compared to vaginal cells derived from asymptomatic women with normal pelvic floor support (control-HVCs). METHODS: Vaginal tissue biopsies were collected from premenopausal patients with POP (n = 8) and asymptomatic controls (n = 7) during vaginal hysterectomy or repair...
July 2016: Reproductive Sciences
Signe Horn, Jeannette S Kirkegaard, Soraya Hoelper, Philip A Seymour, Claude Rescan, Jens H Nielsen, Ole D Madsen, Jan N Jensen, Marcus Krüger, Mads Grønborg, Jonas Ahnfelt-Rønne
Diabetes is characterized by insulin insufficiency due to a relative paucity of functional β-cell mass. Thus, strategies for increasing β-cell mass in situ are sought-after for therapeutic purposes. Pregnancy is a physiological state capable of inducing robust β-cell mass expansion, however, the mechanisms driving this expansion are not fully understood. Thus, the aim of this study was to characterize pregnancy-induced changes in the islet proteome at the peak of β-cell proliferation in mice. Islets from pregnant and nonpregnant littermates were compared via 2 proteomic strategies...
January 2016: Molecular Endocrinology
Eva Adamova, Eva Janeckova, Karel Kleparnik, Eva Matalova
Caspases, well-known players in apoptosis or inflammation, appear to have roles also in other processes such as cell differentiation. Caspase-3, in particular, was recently demonstrated to have non-apoptotic functions in osteogenesis. However, the molecular pathways involved are not yet known. Therefore, we used osteogenic PCR arrays to provide a comprehensive screening of possible interactions of caspases in general and specifically of caspase-3 in osteogenic networks. Embryonic micromass cultures derived from mouse forelimbs were established and pharmacological fluoromethylketone (FMK) inhibitors applied...
February 2016: In Vitro Cellular & Developmental Biology. Animal
D Lauritano, A Avantaggiato, V Candotto, F Cura, R M Gaudio, M Martinelli, A Palmieri
Insulin is a powerful and important hormone involved in the proliferation and differentiation of osteoblasts. Dental pulp stem cells (DPSCs) have the ability to self-expand and differentiate in pre-osteoblast, producing in vitro autologous bone tissue. The aim of our study is to investigate whether insulin can influence differentiation of DPSCs in osteoblast and bone tissue. Dental germ pulp was extracted from third molars of healthy subjects, following informed consent. DPSCs were treated with insulin at the concentration of 100 ng/μl for 24 and 48 h...
July 2015: Journal of Biological Regulators and Homeostatic Agents
I Sukhotnik, D Berkowitz, T Dorfman, Salim Halabi, Y Pollak, J Bejar, A Bitterman, A G Coran
PURPOSE: Bone morphogenetic proteins (BMPs) are a group of growth factors that are implicated in intestinal growth, morphogenesis, differentiation, and homeostasis. The role of the BMP signaling cascade in stimulation of cell proliferation after massive small bowel resection is unknown. The purpose of this study was to evaluate the role of BMP signaling during intestinal adaptation in a rat model of short bowel syndrome (SBS). METHODS: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75 % bowel resection...
February 2016: Pediatric Surgery International
Martin Wein, Tobias Fretwurst, Susanne Nahles, Fabian Duttenhoefer, Pascal Tomakidi, Thorsten Steinberg, Katja Nelson
In oral and maxillofacial surgery, autologous grafts from the iliac crest remain the 'gold standard' for alveolar ridge reconstruction, whereas intraoral bone grafts are considered in smaller defects. To date, a comparison of the osteogenic potential of osteoblasts with regard to their tissue origin is missing. Primary osteoblasts have proven useful for the investigation of the tissue-specific osteogenic properties. The present study compares primary human alveolar (aHOBs) and iliac osteoblasts (iHOBs) derived from three female patients undergoing routine intraoral bone grafting...
October 2015: Journal of Cranio-maxillo-facial Surgery
Suha Turkmen, Aynur Sahin, Mucahit Gunaydin, Sinan Sahin, Ahmet Mentese, Suleyman Turedi, Suleyman Caner Karahan, Savas Ozsu, Abdulkadir Gunduz
OBJECTIVES: The diagnosis of pulmonary embolism (PE) in the emergency department still poses difficulties because symptoms and signs are nonspecific. There is a need for more reliable noninvasive diagnostic tests to support clinical suspicion before the costly invasive procedures with complication risks still used in the diagnosis of PE. Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor) domain-containing protein 1 (SCUBE1) is a novel, secreted cell surface protein expressed during early embryogenesis...
August 2015: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
Noha Sharafeldin, Martha L Slattery, Qi Liu, Conrado Franco-Villalobos, Bette J Caan, John D Potter, Yutaka Yasui
BACKGROUND: Genetic association studies have traditionally focused on associations between individual single nucleotide polymorphisms (SNPs) and disease. Standard analysis ignores interactions between multiple SNPs and environmental exposures explaining a small portion of disease heritability: the often-cited issue of "missing heritability." METHODS: We present a novel three-step analytic framework for modeling gene-environment interactions (GEIs) between an angiogenesis candidate-gene pathway and three lifestyle exposures (dietary protein, smoking, and alcohol consumption) on colon cancer risk and survival...
September 2015: Journal of the National Cancer Institute
Ricquita D Pollard, Christopher N Blesso, Manal Zabalawi, Brian Fulp, Mark Gerelus, Xuewei Zhu, Erica W Lyons, Nebil Nuradin, Omar L Francone, Xiang-An Li, Daisy Sahoo, Michael J Thomas, Mary G Sorci-Thomas
Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis...
June 19, 2015: Journal of Biological Chemistry
Chiang-Ting Chou, Yue-Ju Li, Cheng-Chi Chang, Cheng-Ning Yang, Pei-Shan Li, Yung-Ming Jeng, Szu-Ta Chen, Min-Liang Kuo, I-Ching Lin, Been-Ren Lin
BACKGROUND: To assess the correlations and functions of complement C1r/C1s, Uegf, Bmp1 domain-containing protein-1 (CDCP1) in identifying colorectal cancer (CRC) patients who are at high risk for metastasis. METHODS: Tumor specimens from 101 patients were analyzed by real-time polymerase chain reaction to detect CDCP1 expression. CDCP1 expression plasmids and shRNA were used to knock down CDCP1 expression in this study to investigate migratory and invasive abilities by Boyden chambers...
December 2015: Annals of Surgical Oncology
Roseli da Silva, Miyuki Uno, Suely K Nagahashi Marie, Sueli M Oba-Shinjo
Lysyl oxidase (LOX) is involved in vital biological processes such as cell motility, cell signaling and gene regulation. Deregulation of this protein can contribute to tumor formation and progression. Although it is known that LOX is involved in invasion, proliferation and tumor migration in other types of tumors, studies of LOX in astrocytomas of different grades are scarce. The purpose of our study was to characterize LOX, BMP1 and HIF1A expression by real-time PCR in astrocytomas with WHO grades I to IV compared to non-neoplastic brain tissue...
2015: PloS One
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