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Xiaodan Yu, Hiroko Kawakami, Naoyuki Tahara, Merissa Olmer, Shinichi Hayashi, Ryutaro Akiyama, Anindya Bagchi, Martin Lotz, Yasuhiko Kawakami
Increasing evidence supports the idea that bone morphogenetic proteins (BMPs) regulate cartilage maintenance in the adult skeleton. The aim of this study is to obtain insight into the regulation of BMP activities in the adult skeletal system. We analyzed expression of Noggin and Gremlin1, BMP antagonists that are known to regulate embryonic skeletal development, in the adult skeletal system by Noggin-LacZ and Gremlin1-LacZ knockin reporter mouse lines. Both reporters are expressed in the adult skeleton in a largely overlapping manner with some distinct patterns...
October 21, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Hye-Jin Tak, Tae-Jin Park, Piao Zhengguo, Sang-Hwy Lee
BACKGROUND: Syngnathia is a congenital craniofacial disorder characterized by bony or soft tissue fusion of upper and lower jaws. Previous studies suggested some causative signals, such as Foxc1 or Bmp4, cause the disruption of maxillomandibular identity, but their location and the interactive signals involved remain unexplored. We thus wanted to examine the embryonic origin of syngnathia based on the assumption that it may be located at the separation between the maxillary and mandibular processes...
October 18, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Koichi Ichikawa, Yoichi Ohta, Kenji Mamoto, Shigekazu Mizokawa, Yukihide Minoda, Yuuki Imai, Kunio Takaoka, Hiroaki Nakamura
Bone Morphogenetic Proteins (BMPs) strongly induce the recruitment and differentiation of mesenchymal progenitor cells into mature osteoblasts, but also directly and indirectly stimulate differentiation of osteoclast progenitor cells and acceleration of mature osteoclasts function leading excessive bone resorption. Bisphosphonates, such as zoledronate (ZOL), inhibit osteoclasts function and osteoclasts mediated bone resorption. The short or middle term effect of BMPs and bisphosphonates on bone formation were previously reported, but there was no study that argue about the long term effect of bisphosphonates on BMP-induced bone anabolism...
October 13, 2016: Biochemical and Biophysical Research Communications
Paul Kostenuik, Faisal M Mirza
Delayed healing and nonunion of fractures represent enormous burdens to patients and healthcare systems. There are currently no approved pharmacological agents for the treatment of established nonunions, or for the acceleration of fracture healing, and no pharmacological agents are approved for promoting the healing of closed fractures. Yet several pharmacologic agents have the potential to enhance some aspects of fracture healing. In preclinical studies, various agents working across a broad spectrum of molecular pathways can produce larger, denser and stronger fracture calluses...
October 15, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Monique Ae Schoeman, Angela E Oostlander, Karien E de Rooij, Edward R Valstar, Rob Ghh Nelissen
During the process of aseptic loosening of prostheses, particulate wear debris induces a continuous inflammatory-like response resulting in the formation of a layer of fibrous peri-prosthetic tissue at the bone-prosthesis interface. The current treatment for loosening is revision surgery which is associated with a high morbidity rate, especially in old patients. Therefore, less invasive alternatives are necessary. One approach could be to re-establish osseointegration of the prosthesis by inducing osteoblast differentiation in the peri-prosthetic tissue...
October 7, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Kuei-Chang Li, Shih-Chun Lo, Li-Yu Sung, Ya-Hsin Liao, Yu-Han Chang, Yu-Chen Hu
Repairing large calvarial bone defects remains a challenging task. Previously, it was discovered that that miR-148b, when acting in concert with bone morphogenetic protein 2 (BMP-2), enhanced the osteogenesis of human adipose-derived stem cells (hASCs) and improved calvarial bone healing in nude mice. However, the molecular target of miR-148b remained elusive. Here it is revealed that miR-148b directly targets NOG, whose gene product (noggin) is an antagonist to BMPs and negatively regulates BMP-induced osteogenic differentiation and bone formation...
September 30, 2016: Journal of Tissue Engineering and Regenerative Medicine
Claudio A Franco, Holger Gerhardt
Bone morphogenic proteins (BMPs) and blood flow regulate vascular remodeling and homeostasis. In this issue, Baeyens et al. (2016. J. Cell Biol show that blood flow sensitizes endothelial cells to BMP9 signaling by triggering Alk1/ENG complexing to suppress cell proliferation and to recruit mural cells, thereby establishing endothelial quiescence.
September 26, 2016: Journal of Cell Biology
Lijie Zhang, Yingnan Ye, Xinxin Long, Pei Xiao, Xiubao Ren, Jinpu Yu
Bone morphogenetic proteins (BMPs) play important roles in embryonic and postnatal development by regulating cell differentiation, proliferation, motility, and survival, thus maintaining homeostasis during organ and tissue development. BMPs can lead to tumorigenesis and regulate cancer progression in different stages. Therefore, we summarized studies on BMP expression, the clinical significance of BMP dysfunction in various cancer types, and the molecular regulation of various BMP-related signaling pathways...
September 20, 2016: Oncotarget
Ugo Ripamonti, Raquel Duarte, Ruqayya Parak, Caroline Dickens, Therese Dix-Peek, Roland M Klar
The soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β) supergene family are the molecular bases of the induction of bone formation and postnatal bone tissue morphogenesis with translation into clinical contexts. The mammalian TGF-β3 isoform, a pleiotropic member of the family, controls a vast array of biological processes including the induction of bone formation. Recombinant hTGF-β3 induces substantial bone formation when implanted with either collagenous bone matrices or coral-derived macroporous bioreactors in the rectus abdominis muscle of the non-human primate Papio ursinus...
2016: Frontiers in Physiology
Zhenhua Ma, Nan Zhang, Jian G Qin, Mingjun Fu, Shigui Jiang
Golden pompano Trachinotus ovatus larvae were kept at 26, 29 and 33 °C for 15 days from 3-day post hatching (DPH) to 18 DPH to test temperature-dependent growth and jaw malformation. The growth, survival, jaw deformity and the gene expressions of bone morphogenetic proteins (BMPs) were used as criteria to examine the fish response to temperature manipulation. The growth rate of fish at 29 or 33 °C was significantly faster than fish at 26 °C, while fish survival at 29 °C was significantly higher than fish at 33 °C...
2016: SpringerPlus
Nicolas Baeyens, Bruno Larrivée, Roxana Ola, Brielle Hayward-Piatkowskyi, Alexandre Dubrac, Billy Huang, Tyler D Ross, Brian G Coon, Elizabeth Min, Maya Tsarfati, Haibin Tong, Anne Eichmann, Martin A Schwartz
Morphogenesis of the vascular system is strongly modulated by mechanical forces from blood flow. Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal-dominant disease in which arteriovenous malformations and telangiectasias accumulate with age. Most cases are linked to heterozygous mutations in Alk1 or Endoglin, receptors for bone morphogenetic proteins (BMPs) 9 and 10. Evidence suggests that a second hit results in clonal expansion of endothelial cells to form lesions with poor mural cell coverage that spontaneously rupture and bleed...
September 26, 2016: Journal of Cell Biology
Jeong-Seok Kim, Young-Hee Lee, Ho-Keun Yi
Recent evidence suggests that autophagy and bone morphogenetic protein signaling pathway regulate skeletal muscle growth and bone formation in aged rats. However, the effect of downhill running on muscle growth and bone formation is not well understood. Thus, we investigated the effect of downhill and uphill running on age-related muscle and bone weakness. Young and late middle-aged rats were randomly assigned to control groups; young (YC) and late middle-aged (LMC), and two types of running training groups: late middle-aged downhill (LMD) and late middle-aged uphill (LMU)...
September 19, 2016: Experimental Physiology
Flora Gilde, Laure Fourel, Raphael Guillot, Isabelle Pignot-Paintrand, Takaharu Okada, Vincent Fitzpatrick, Thomas Boudou, Corinne Albiges-Rizo, Catherine Picart
: Surface coatings delivering BMP are a promising approach to render biomaterials osteoinductive. In contrast to soluble BMPs which can interact with their receptors at the dorsal side of the cell, BMPs presented as an insoluble cue physically bound to a biomimetic matrix, called here matrix-bound (bBMP-2), are presented to cells by their ventral side. To date, BMP-2 internalization and signaling studies in cell biology have always been performed by adding soluble (sBMP-2) to cells adhered on cell culture plates or glass slides, which will be considered here as a "reference" condition...
September 12, 2016: Acta Biomaterialia
Wendong Ruan, Yuan Xue, Yaqi Zong, Chao Sun
In the present study, third‑generation autologous‑inactivated bone morphogenic protein 2 (BMP2), BMP4, BMP6, BMP7, BMP9 and Wnt3a lentiviral vectors were constructed and integrated into the genome of MC3T3‑E1 murine mesenchymal stem cells (MMSCs) to produce osteoinductive factor gene‑modified MMSCs. The transfection efficiency of each osteoinductive factor was then determined by detecting the expression levels of runt related transcription factor 2 (Runx2) mRNA. The cotransfection with combinations of two lentiviruses was performed, and the expression levels of bone γ‑carboxyglutamate protein and alkaline phosphatase in the MC3T3‑E1 cell culture supernatant were detected...
September 12, 2016: Molecular Medicine Reports
Sébastien A B Roy, Joannie M Allaire, Camille Ouellet, Faiza Maloum-Rami, Véronique Pomerleau, Étienne Lemieux, Jean-Philippe Babeu, Jasmin Rousseau, Marilène Paquet, Perrine Garde-Granger, François Boudreau, Nathalie Perreault
Bmps are morphogens involved in various gastric cellular functions. Studies in genetically-modified mice have shown that Bmp disruption in gastric epithelial and stromal cell compartments leads to the development of tumorigenesis. Our studies have demonstrated that abrogation of gastric epithelial Bmp signaling alone was not sufficient to recapitulate the neoplastic features associated with total gastric loss of Bmp signaling. Thus, epithelial Bmp signaling does not appear to be a key player in gastric tumorigenesis initiation...
2016: Scientific Reports
Atilgan Yilmaz, Chandramohan Kattamuri, Rana N Ozdeslik, Carolyn Schmiedel, Sarah Mentzer, Christoph Schorl, Elena Oancea, Thomas B Thompson, Justin R Fallon
Bone morphogenetic proteins (BMPs) function in most tissues but have cell type-specific effects. Given the relatively small number of BMP receptors, this exquisite signaling specificity requires additional molecules to regulate this pathway's output. The receptor tyrosine kinase MuSK (muscle-specific kinase) is critical for neuromuscular junction formation and maintenance. Here, we show that MuSK also promotes BMP signaling in muscle cells. MuSK bound to BMP4 and related BMPs with low nanomolar affinity in vitro and to the type I BMP receptors ALK3 and ALK6 in a ligand-independent manner both in vitro and in cultured myotubes...
2016: Science Signaling
Hugo Urrutia, Abigail Aleman, Edward Eivers
Bone morphogenetic proteins (BMPs) are growth factors that provide essential signals for normal embryonic development and adult tissue homeostasis. A key step in initiating BMP signaling is ligand induced phosphorylation of receptor Smads (R-Smads) by type I receptor kinases, while linker phosphorylation of R-Smads has been shown to cause BMP signal termination. Here we present data demonstrating that the phosphatase Dullard is involved in dephosphorylating the Drosophila R-Smad, Mad, and is integral in controlling BMP signal duration...
2016: Scientific Reports
Greg Kleinheinz, Jorge Hernandez
The increased interest in anaerobic digestion systems has led to the increased need for laboratories to conduct biomethane potential (BMP) to determine the possible usefulness of various feedstocks. There is currently no standard method, but two well established methods have emerged as standardized methods for BMP testing. These two methods are the Automated Methane Potential Testing System, or AMPTS and the German DIN standard method using eudiometers. While these are widely-used, there have been no comparison of how these systems relate to each other in terms of BMP results for identical feedstocks...
November 2016: Journal of Microbiological Methods
Jiangfeng Liu, Weiling Wang, Ming Liu, Limin Su, Hong Zhou, Yin Xia, Jianhua Ran, Herbert Y Lin, Baoxue Yang
Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disease that still lacks effective therapy. Repulsive guidance molecule b (RGMb), a co-receptor for bone morphogenetic proteins (BMPs) and a ligand for neogenin, is expressed in renal tubular epithelial cells. Previous studies showed that RGMb plays negative roles in several types of tumors and prevents the immune system from over activation. The present study was designed to explore the effects of RGMb in ADPKD development. We found that expression of RGMb in kidney was less in PKD mice than wild-type mice...
December 2016: Cellular Signalling
Domiziana Costamagna, Hendrik Mommaerts, Maurilio Sampaolesi, Przemko Tylzanowski
Inactivation of Noggin, a secreted antagonist of Bone Morphogenetic Proteins (BMPs), in mice leads, among others, to severe malformations of the appendicular skeleton and defective skeletal muscle fibers. To determine the molecular basis of the phenotype, we carried out a histomorphological and molecular analysis of developing muscles Noggin(-/-) mice. We show that in 18.5 dpc embryos there is a marked reduction in muscle fiber size and a failure of nuclei migration towards the cell membrane. Molecularly, the absence of Noggin results in an increased BMP signaling in muscle tissue as shown by the increase in SMAD1/5/8 phosphorylation, concomitant with the induction of BMP target genes such as Id1, 2, 3 as well as Msx1...
2016: Scientific Reports
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