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Bone morphogenetic protein

Rahel D May, Daniela A Frauchiger, Christoph E Albers, Lorin M Benneker, Sandro Kohl, Benjamin Gantenbein
Spinal fusion is a common surgical procedure to address a range of spinal pathologies, like damaged or degenerated discs. After the removal of the intervertebral disc (IVD), a structural spacer is positioned followed by internal fixation, and fusion of the degenerated segment by natural bone growth. Due to their osteoinductive properties, bone morphogenetic proteins (BMP) are applied to promote spinal fusion. Although spinal fusion is successful in most patients, the rates of non-unions after lumbar spine fusion range from 5% to 35%...
April 13, 2018: International Journal of Molecular Sciences
Marc Coughlan, Mark Davies, Adriaan K Mostert, Dharmin Nanda, Paul C Willems, Geoffrey Rosenberg, Richard Ferch
STUDY DESIGN: A prospective, Phase IV, multicenter, randomized study. OBJECTIVE: To compare vertebral fusion success rates following posterolateral fusion ((PLF)/posterolateral intertransverse fusion (PITF)) surgery. The surgical procedure combined posterior lumbar interbody fusion (PLIF) and PLF with internal fixation over one or two levels using silicated calcium phosphate (SiCaP) or bone morphogenetic protein (BMP)-2 as graft material in patients with a degenerative disorder of the lumbar spine...
April 12, 2018: Spine
Stefan Gräf, Matthias Haimel, Marta Bleda, Charaka Hadinnapola, Laura Southgate, Wei Li, Joshua Hodgson, Bin Liu, Richard M Salmon, Mark Southwood, Rajiv D Machado, Jennifer M Martin, Carmen M Treacy, Katherine Yates, Louise C Daugherty, Olga Shamardina, Deborah Whitehorn, Simon Holden, Micheala Aldred, Harm J Bogaard, Colin Church, Gerry Coghlan, Robin Condliffe, Paul A Corris, Cesare Danesino, Mélanie Eyries, Henning Gall, Stefano Ghio, Hossein-Ardeschir Ghofrani, J Simon R Gibbs, Barbara Girerd, Arjan C Houweling, Luke Howard, Marc Humbert, David G Kiely, Gabor Kovacs, Robert V MacKenzie Ross, Shahin Moledina, David Montani, Michael Newnham, Andrea Olschewski, Horst Olschewski, Andrew J Peacock, Joanna Pepke-Zaba, Inga Prokopenko, Christopher J Rhodes, Laura Scelsi, Werner Seeger, Florent Soubrier, Dan F Stein, Jay Suntharalingam, Emilia M Swietlik, Mark R Toshner, David A van Heel, Anton Vonk Noordegraaf, Quinten Waisfisz, John Wharton, Stephen J Wort, Willem H Ouwehand, Nicole Soranzo, Allan Lawrie, Paul D Upton, Martin R Wilkins, Richard C Trembath, Nicholas W Morrell
Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-β pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH...
April 12, 2018: Nature Communications
Qingqing Yao, Yangxi Liu, Balaranjan Selvaratnam, Ranjit T Koodali, Hongli Sun
Controlled delivery systems play a critical role in the success of bone morphogenetic proteins (i.e., BMP2 and BMP7) for challenged bone repair. Instead of single-drug release that is currently and commonly prevalent, dual-drug delivery strategies are highly desired to achieve effective bone regeneration because natural bone repair process is driven by multiple factors. Particularly, angiogenesis is essential for osteogenesis and requires more than just one factor (e.g., Vascular Endothelial Growth Factor, VEGF)...
April 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Linyuan Fan, Junfen Fan, Yan Liu, Tangping Li, Haoying Xu, Yanlei Yang, Luchan Deng, Hongling Li, Robert Chunhua Zhao
Osteoporosis is characterized by deterioration of bone microarchitecture and low bone mass. One of the primary causes of osteoporosis is the decrease in the osteogenic differentiation of mesenchymal stem cells. Tissue engineering therapy with genetically modified mesenchymal stem cells has attracted much attention in the study of bone regeneration. In this study, we found that the expression level of miR-450b was upregulated during osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs)...
March 16, 2018: Stem Cells and Development
Liyao Gou, Mengyao Liu, Jing Xia, Qun Wan, Yayun Jiang, Shilei Sun, Min Tang, Lan Zhou, Tongchuan He, Yan Zhang
As the most common malignant tumor of the urinary system worldwide, the bladder tumor has a high mortality rate, which is mainly due to its onset of concealment. Therefore, research into novel diagnostic markers and treatment of bladder cancer is urgently needed. BMP9 (Bone morphogenetic protein 9) is a member of BMP, which belongs to the TGF-β (transforming growth factor-β) superfamily. It has been associated with multiple tumors. We found that BMP9 is highly expressed in bladder cancer cells and it could significantly promote the proliferation and migration of bladder cancer cells...
April 8, 2018: International Journal of Molecular Sciences
An-Chen Chang, Po-Chun Chen, Yu-Feng Lin, Chen-Ming Su, Ju-Fang Liu, Tien-Huang Lin, Show-Mei Chuang, Chih-Hsin Tang
Bone metastasis is a frequent occurrence in prostate cancer (PCa) that is associated with severe complications such as fracture, bone pain and hypercalcemia. The cross-talk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. In our previous data, we have described how the involvement of the Wnt-induced secreted protein-1/vascular cell adhesion molecule-1 (WISP-1/VCAM-1) system in this tumor-bone interaction contributes to human PCa cell motility. In this study, we found that WISP-1 regulates bone mineralization by inducing bone morphogenetic protein-2 (BMP2), BMP4 and osteopontin (OPN) expression in osteoblasts...
April 5, 2018: Cancer Letters
Guorong Lu, Mary R Tandang-Silvas, Alyssa C Dawson, Trenton J Dawson, Jay C Groppe
Heterotopic ossification (HO), the pathological extraskeletal formation of bone, can arise from blast injuries, severe burns, orthopedic procedures and gain-of-function mutations in a component of the bone morphogenetic protein (BMP) signaling pathway, the ACVR1/ALK2 receptor serine-threonine (protein) kinase, causative of Fibrodysplasia Ossificans Progressiva (FOP). All three ALKs (-2, -3, -6) that play roles in bone morphogenesis contribute to trauma-induced HO, hence are well-validated pharmacological targets...
April 4, 2018: Bone
Jenna H Newman, David J Augeri, Rachel NeMoyer, Jyoti Malhotra, Elaine Langenfeld, Charles B Chesson, Natalie S Dobias, Michael J Lee, Saeed Tarabichi, Sachin R Jhawar, Praveen K Bommareddy, Sh'Rae Marshall, Evita T Sadimin, John E Kerrigan, Michael Goedken, Christine Minerowicz, Salma K Jabbour, Shengguo Li, Mary O Carayannopolous, Andrew Zloza, John Langenfeld
BMP receptor inhibitors induce death of cancer cells through the downregulation of antiapoptotic proteins XIAP, pTAK1, and Id1-Id3. However, the current most potent BMP receptor inhibitor, DMH2, does not downregulate BMP signaling in vivo because of metabolic instability and poor pharmacokinetics. Here we identified the site of metabolic instability of DMH2 and designed a novel BMP receptor inhibitor, JL5. We show that JL5 has a greater volume of distribution and suppresses the expression of Id1 and pTak1 in tumor xenografts...
April 6, 2018: Oncogene
Christina Mundy, Evan Yang, Hajime Takano, Paul C Billings, Maurizio Pacifici
Hereditary Multiple Exostoses (HME) is a pediatric disorder caused by heparan sulfate (HS) deficiency and is characterized by growth plate-associated osteochondromas. Previously, we found that osteochondroma formation in mouse models is preceded by ectopic bone morphogenetic protein (BMP) signaling in the perichondrium, but the mechanistic relationships between BMP signaling and HS deficiency remain unclear. Therefore, we used an HS antagonist (Surfen) to investigate the effects of this HS interference on BMP signaling, ligand availability, cell surface BMP receptor (BMPR) dynamics and BMPR interactions in Ad-293 and C3H/10T1/2 cells...
April 5, 2018: Journal of Biological Chemistry
Alexandre Janin, Delphine Bauer, Francesca Ratti, Camille Valla, Anne Bertrand, Emilie Christin, Emilie Chopin, Nathalie Streichenberger, Gisèle Bonne, Vincent Gache, Tatiana Cohen, Alexandre Méjat
LMNA gene encodes lamins A and C, two major components of the nuclear lamina, a network of intermediate filaments underlying the inner nuclear membrane. Most of LMNA mutations are associated with cardiac and/or skeletal muscles defects. Muscle laminopathies include Emery-Dreifuss Muscular Dystrophy, Limb-Girdle Muscular Dystrophy 1B, LMNA-related Congenital Muscular Dystrophy and Dilated Cardiomyopathy with conduction defects. To identify potential alterations in signaling pathways regulating muscle differentiation in LMNA-mutated myoblasts, we used a previously described model of conditionally immortalized murine myoblasts: H-2K cell lines...
April 4, 2018: Scientific Reports
Kotaro Horiguchi, Ken Fujiwara, Saishu Yoshida, Takashi Nakakura, Ken Arae, Takehiro Tsukada, Rumi Hasegawa, Shu Takigami, Shunji Ohsako, Takashi Yashiro, Takako Kato, Yukio Kato
S100β protein and SOX2-double positive (S100β/SOX2-positive) cells have been suggested to be adult pituitary stem/progenitor cells exhibiting plasticity and multipotency. The aim of the present study was to isolate S100β/SOX2-positive cells from the adult anterior lobes of rats using a specific antibody against a novel membrane marker and to study their characteristics in vitro. We found that cluster of differentiation (CD) 9 is expressed in the majority of adult rat S100β/SOX2-positive cells, and we succeeded in isolating CD9-positive cells using an anti-CD9 antibody with a pluriBead-cascade cell isolation system...
April 3, 2018: Scientific Reports
Yoshinori Abe, Nobuyuki Tanaka
The epidermis is the outermost layer of the skin and provides a protective barrier against environmental insults. It is a rapidly-renewing tissue undergoing constant regeneration, maintained by several types of stem cells. The Hedgehog (HH) signaling pathway is one of the fundamental signaling pathways that contributes to epidermal development, homeostasis, and repair, as well as to hair follicle development and follicle bulge stem cell maintenance. The HH pathway interacts with other signal transduction pathways, including those activated by Wnt, bone morphogenetic protein, platelet-derived growth factor, Notch, and ectodysplasin...
November 20, 2017: Journal of Developmental Biology
Elke Malzer, Caia S Dominicus, Joseph E Chambers, Jennifer A Dickens, Souradip Mookerjee, Stefan J Marciniak
BACKGROUND: Developmental pathways must be responsive to the environment. Phosphorylation of eIF2α enables a family of stress-sensing kinases to trigger the integrated stress response (ISR), which has pro-survival and developmental consequences. Bone morphogenetic proteins (BMPs) regulate multiple developmental processes in organisms from insects to mammals. RESULTS: Here we show in Drosophila that GCN2 antagonises BMP signalling through direct effects on translation and indirectly via the transcription factor crc (dATF4)...
April 3, 2018: BMC Biology
Behnaz Bozorgui, Anatoly B Kolomeisky, Hamid Teimouri
Gastrulation is a fundamental phase during the biological development of most animals when a single layer of identical embryo cells is transformed into a three-layer structure, from which the organs start to develop. Despite a remarkable progress in quantifying the gastrulation processes, molecular mechanisms of these processes remain not well understood. Here we theoretically investigate early spatial patterning in a geometrically confined colony of embryonic stem cells. Using a reaction-diffusion model, a role of Bone-Morphogenetic Protein 4 (BMP4) signaling pathway in gastrulation is specifically analyzed...
March 28, 2018: Journal of Chemical Physics
Yushu Zhang, Chuanlian Zhang, Kemiao Liu, Xia Zhu, Fang Liu, Xiaofen Ge
The aim of the present study is to develop novel approach for the green synthesis of titanium oxide nanoparticles (TiO2 NPs) using Eichhornia crassipes extract and calcined at different temperatures for evaluate the wound healing activity in the femoral fracture. The synthesized TiO2 are formed different (plate and rod-like) nanostructures at various calcination temperatures. These samples were characterized by X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR), Field emission scanning electron microscope (FE-SEM) and transmission electron microscope (TEM)...
March 6, 2018: Journal of Photochemistry and Photobiology. B, Biology
Maurits G L Olthof, Diederik H R Kempen, Xifeng Liu, Mahrokh Dadsetan, Marianna A Tryfonidou, Michael J Yaszemski, Wouter J A Dhert, Lichun Lu
The optimal release profile of locally delivered BMP-2 for safe and effective clinical application is unknown. In this work, the effect of differential BMP-2 release on bone formation was investigated using a novel biomaterial oligo[(polyethylene glycol) fumarate] bis[2-(methacryloyloxy) ethyl] phosphate hydrogel (OPF-BP) containing poly(lactic-co-glycolic acid) microspheres. Three composite implants with same biomaterial chemistry and structure but different BMP-loading methods were created: BMP-2 encapsulated in microspheres (OPF-BP-Msp), BMP-2 encapsulated in microspheres and adsorbed on the phosphorylated hydrogel (OPF-BP-Cmb), and BMP-2 adsorbed on the phosphorylated hydrogel (OPF-BP-Ads)...
March 31, 2018: Journal of Tissue Engineering and Regenerative Medicine
Tristan T Hays, Ben Ma, Ning Zhou, Shaunrick Stoll, William J Pearce, Hongyu Qiu
Aortic stiffening is an independent risk factor that underlies cardiovascular morbidity in the elderly. We have previously shown that intrinsic mechanical properties of vascular smooth muscle cells (VSMCs) play a key role in aortic stiffening in both aging and hypertension. Here, we test the hypothesis that VSMCs also contribute to aortic stiffening through their extracellular effects. Aortic stiffening was confirmed in spontaneously hypertensive rats (SHRs) vs. Wistar-Kyoto (WKY) rats in vivo by echocardiography and ex vivo by isometric force measurements in isolated de-endothelized aortic vessel segments...
March 30, 2018: Aging Cell
Soyon Kim, Zhong-Kai Cui, Paul Jay Kim, Lawrence Young Jung, Min Lee
Although bone morphogenetic protein-2 (BMP-2) is known to be the most potent stimulator available for bone formation, a major barrier to widespread clinical use is its inherent instability and absence of an adequate delivery system. Heparin is being widely used in controlled release systems due to its strong binding ability and protective effect for many growth factor proteins. In this work, we developed a hydrogel surface that can mimic heparin to stabilize BMP-2 and to enhance osteogenesis by introducing heparin-mimicking sulfonated molecules such as poly-vinylsulfonic acid (PVSA) or poly-4-styrenesulfonic acid (PSS), into photo-crosslinkable hydrogel...
March 26, 2018: Acta Biomaterialia
Yunxian Huang, Masatsugu Hatakeyama, Osamu Shimmi
Wing venation among insects serves as an excellent model to address how diversified patterns are produced. Previous studies suggest that evolutionarily conserved Decapentaplegic (Dpp)/Bone Morphogenetic Protein (BMP) signal plays a critical role in wing vein development in the Dipteran Drosophila melanogaster and the Hymenopteran sawfly Athalia rosae. In sawfly, dpp is ubiquitously expressed in the wing during prepupal stages, but Dpp/BMP signal is localized in the future vein cells. Since localized BMP signaling involves BMP binding protein Crossveinless (Cv), redistribution of BMP ligands appears to be crucial for sawfly wing vein formation...
March 26, 2018: Arthropod Structure & Development
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