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J Wang, D Massoudi, Y Ren, A M Muir, S E Harris, D S Greenspan, J Q Feng
Mutations in bone morphogenetic protein 1 (BMP1) in humans or deletion of BMP1 and related protease tolloid like 1 (TLL1) in mice lead to osteogenesis imperfecta (OI). Here, we show progressive periodontal defects in mice in which both BMP1 and TLL1 have been conditionally ablated, including malformed periodontal ligament (PDL) (recently shown to play key roles in normal alveolar bone formation), significant loss in alveolar bone mass ( P < 0.01), and a sharp reduction in cellular cementum. Molecular mechanism studies revealed a dramatic increase in the uncleaved precursor of type I collagen (procollagen I) and a reduction in dentin matrix protein 1 (DMP1), which is partially responsible for defects in extracellular matrix (ECM) formation and mineralization...
January 1, 2017: Journal of Dental Research
Hua Zhang, Priyam Jani, Tian Liang, Yongbo Lu, Chunlin Qin
Bone morphogenetic protein 1 (BMP1) and tolloid-like 1 (TLL1) belong to the BMP1/tolloid-like proteinase family, which cleaves secretory proteins. The constitutive deletion of the Bmp1 or Tll1 genes causes perinatal or embryonic lethality in mice. In this study, we first studied the β-galactosidase activity in mice in which an IRES-lacZ-Neo cassette was inserted in the intron of either the Bmp1 or the Tll1 gene; the β-galactosidase activities were used to reflect the expression of endogenous Bmp1 and Tll1, respectively...
December 20, 2016: Journal of Molecular Histology
Judilyn Fuentes-Duculan, Kathleen M Bonifacio, Mayte Suárez-Fariñas, Norma Kunjravia, Sandra Garcet, Tristan Cruz, Claire Q F Wang, Hui Xu, Patricia Gilleadeau, Mary Sullivan-Whalen, Michael H Tirgan, James G Krueger
Keloids are benign fibroproliferative tumors more frequently found among African Americans. Until now, keloid etiopathogenesis is not fully understood. To characterize keloids in African Americans, we performed transcriptional profiling of biopsies from large chronic keloids, adjacent nonlesional (NL) skin (n=3) and a newly formed keloid lesion using Affymetrix HGU133 2.0 plus arrays. Quantitative RT-PCR (qRT-PCR) and immunohistochemistry staining were done to confirm increased expression of relevant genes...
December 11, 2016: Experimental Dermatology
Xiaocan Lei, Kuiqing Cui, Xiaoyan Cai, Yanping Ren, Qingyou Liu, Deshun Shi
In the present study, we tried to determine whether bone morphogenetic protein 1 (BMP1) plays a role in ovarian follicular development and early embryo development. We systematically investigated the expression and influence of BMP1 during porcine follicle and early embryonic development. Immunohistochemistry demonstrated that the BMP1 protein is expressed in granular cells and oocytes during follicular development, from primary to pre-ovulatory follicles, including atretic follicles and the corpus luteum. The mRNA expression of BMP1 significantly increased as the porcine follicles grew...
November 25, 2016: Journal of Veterinary Medical Science
Jun Wang, Alison M Muir, Yinshi Ren, Dawiyat Massoudi, Daniel S Greenspan, Jian Q Feng
INTRODUCTION: Mutations in the proteinase bone morphogenetic protein-1 (BMP1) were recently identified in patients with osteogenesis imperfecta, which can be associated with type 1 dentinogenesis imperfecta. BMP1 is co-expressed in various tissues and has overlapping activities with the closely related proteinase mammalian tolloid-like 1 (TLL1). In this study we investigated whether removing the overlapping activities of BMP1 and TLL1 affects the mineralization of tooth root dentin. METHODS: Floxed alleles of the BMP1 and TLL1 genes were excised via ubiquitously expressed Cre induced by tamoxifen treatment beginning at 3 days of age (harvested at 3 weeks of age) or beginning at 4 weeks of age (harvested at 8 weeks of age)...
January 2017: Journal of Endodontics
Nigar Dirican, Ali Duman, Gülcan Sağlam, Akif Arslan, Onder Ozturk, Sule Atalay, Ahmet Bircan, Ahmet Akkaya, Munire Cakir
BACKGROUND: Pulmonary embolism (PE) is a common and potentially life-threatening disorder. Patients with PE often have nonspecific symptoms, and the diagnosis is often delayed. AIM: The aim of our study was to investigate the role of signal peptide-complement C1r/C1s, Uegf, and Bmp1-epidermal growth factor domain-containing protein 1 (SCUBE1) used in the diagnosis of PE. METHODS: The study was designed prospectively. A total of 57 patients who were admitted to emergency service with clinically suspected PE were included in the study...
October 2016: Annals of Thoracic Medicine
György Szláma, Viktor Vásárhelyi, Mária Trexler, László Patthy
: The NTR domain of WFIKKN1 protein has been shown to have significant affinity for the prodomain regions of promyostatin and latent myostatin but the biological significance of these interactions remained unclear. In view of its role as a myostatin antagonist, we tested the assumption that WFIKKN1 inhibits the release of myostatin from promyostatin and/or latent myostatin. WFIKKN1 was found to have no effect on processing of promyostatin by furin, the rate of cleavage of latent myostatin by BMP1, however, was significantly enhanced in the presence of WFIKKN1 and this enhancer activity was superstimulated by heparin...
December 2016: FEBS Journal
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...
January 2017: 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...
December 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...
December 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
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