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Leandra Santos Baptista, Gabriela Soares Kronemberger, Karina Ribeiro Silva, Jose Mauro Granjeiro
Osteodegenerative disease and bone fractures lead to bone damage or loss, requiring new bone formation to replace the damaged tissues. Classical 'top-down' tissue engineering relies on seeding cell suspensions into biomaterial scaffolds, and then guiding cell fate by growth factors. However, complex tissue fabrication using this approach has important limitations. 'Bottom-up' tissue engineering has the potential to overcome the drawbacks of the top-down approach, by using 'building blocks' of cell spheroids for tissue biofabrication without a scaffold...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
Linnea Schmidt, Aftab Taiyab, Vida Senkus Melvin, Kenneth L Jones, Trevor Williams
The bones of the cranial vault are formed directly from mesenchymal cells through intramembranous ossification rather than via a cartilage intermediate. Formation and growth of the skull bones involves the interaction of multiple cell:cell signaling pathways, with Fibroblast Growth Factors (FGFs) and their receptors exerting prominent influence. Mutations within this pathway are the most frequent cause of craniosynostosis, which is a common human craniofacial developmental abnormality characterized by the premature fusion of the cranial sutures...
May 10, 2018: Disease Models & Mechanisms
Zhirui Jiang, Ainslie L K Derrick-Roberts, Matilda R Jackson, Charné Rossouw, Carmen E Pyragius, Cory Xian, Janice Fletcher, Sharon Byers
Short stature is a characteristic feature of most of the mucopolysaccharidoses, a group of inherited lysosomal storage disorders caused by a single enzyme deficiency. MPS patients present with progressive skeletal defects from an early age, including short stature due to impaired cartilage-to-bone conversion (endochondral ossification). The aim of this study was to determine which murine MPS model best reproduces the bone length reduction phenotype of human MPS and use this model to determine the earliest developmental stage when disrupted endochondral ossification first appears...
May 3, 2018: Molecular Genetics and Metabolism
Masataka Kasai, Reiko Ishida, Kazuhiko Nakahara, Ko Okumura, Katsunori Aoki
Translin and translin-associated factor X (translin/TRAX) proteins have been implicated in a variety of cellular activities central to nucleic acid metabolism. Accumulating evidence indicates that translin/TRAX complexes participate in processes ensuring the replication of DNA, as well as cell division. Significant progress has been made in understanding the roles of translin/TRAX complexes in RNA metabolism, such as through RNA-induced silencing complex activation or the microRNA depletion that occurs in Dicer deficiency...
May 8, 2018: Annals of the New York Academy of Sciences
Jianyun Yan, Jun Li, Jun Hu, Lu Zhang, Chengguo Wei, Nishat Sultana, Xiaoqiang Cai, Weijia Zhang, Chen-Leng Cai
Chondrocyte hypertrophy is the terminal step in chondrocyte differentiation and is crucial for endochondral bone formation. How signaling pathways regulate chondrocyte hypertrophic differentiation remains incompletely understood. In this study, using a Tbx18:Cre (Tbx18Cre/+) gene-deletion approach, we selectively deleted the gene for the signaling protein SMAD family member 4 (Smad4f/f) in the limbs of mice. We found that the Smad4-deficient mice develop a prominent shortened limb, with decreased expression of chondrocyte differentiation markers, including Col2a1 and Acan, in the humerus at mid-to-late gestation...
May 7, 2018: Journal of Biological Chemistry
Yinxiang Wang, Jessica Aijia Liu, Keith K H Leung, Mai Har Sham, Danny Chan, Kathryn S E Cheah, Martin Cheung
Previous studies have demonstrated the ability of reprogramming endochondral bone into induced pluripotent stem (iPS) cells, but whether similar phenomenon occurs in intramembranous bone remains to be determined. Here we adopted fluorescence-activated cell sorting-based strategy to isolate homogenous population of intramembranous calvarial osteoblasts from newborn transgenic mice carrying both Osx1-GFP::Cre and Oct4-EGFP transgenes. Following retroviral transduction of Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc), enriched population of osteoblasts underwent silencing of Osx1-GFP::Cre expression at early stage of reprogramming followed by late activation of Oct4-EGFP expression in the resulting iPS cells...
2018: Stem Cells International
Fernanda Langellotto, Maria Fiorentino, Elena De Felice, Luigi Caputi, Valeria Nittoli, Jean M P Joss, Paolo Sordino
Background: The concerted activity of Meis and Hoxa11 transcription factors is essential for the subdivision of tetrapod limbs into proximo-distal (PD) domains; however, little is know about the evolution of this patterning mechanism. Here, we aim to study the expression of meis and hoxa11 orthologues in the median and paired rayed fins of zebrafish and in the lobed fins of the Australian lungfish. Results: First, a late phase of expression of meis1.1 and hoxa11b in zebrafish dorsal and anal fins relates with segmentation of endochondral elements in proximal and distal radials...
2018: EvoDevo
Chiara Stüdle, Queralt Vallmajó Martín, Alexander Haumer, Julien Guerrero, Matteo Centola, Arne Mehrkens, Dirk J Schaefer, Martin Ehrbar, Andrea Barbero, Ivan Martin
Despite the various reported approaches to generate osteochondral composites by combination of different cell types and materials, engineering of templates with the capacity to autonomously and orderly develop into cartilage-bone bi-layered structures remains an open challenge. Here, we hypothesized that the embedding of cells inducible to endochondral ossification (i.e. bone marrow derived mesenchymal stromal cells, BMSCs) and of cells capable of robust and stable chondrogenesis (i.e. nasal chondrocytes, NCs) adjacent to each other in bi-layered hydrogels would develop directly in vivo into osteochondral tissues...
April 21, 2018: Biomaterials
C H Kiernan, A KleinJan, M Peeters, E B Wolvius, E Farrell, P A J Brama
Bone marrow stromal cell (BMSC) mediated endochondral bone formation may be a promising alternative to the current gold standards of autologous bone transplantation, in the development of novel methods for bone repair. Implantation of chondrogenically differentiated BMSCs leads to bone formation in vivo via endochondral ossification. The success of this bone formation in an allogeneic system depends upon the interaction between the implanted constructs and the host immune system. The current study investigated the effect of chondrogenically differentiated hBMSC pellets on the maturation and function of dendritic cells (DCs) by directly co-culturing bone forming chondrogenic hBMSC pellets and immature or lipopolysaccharide (LPS)-matured DCs in vitro...
April 27, 2018: Journal of Tissue Engineering and Regenerative Medicine
Bettina Kruck, Elizabeth A Zimmermann, Sophie Damerow, Christine Figge, Catherine Julien, Dag Wulstein, Tobias Thiele, Madge Martin, Reggie Hamdy, Marie K Reumann, Georg N Duda, Sara Checa, Bettina M Willie
During bone healing, tissue formation processes are governed by mechanical strain. Sost/sclerostin, a key Wnt signaling inhibitor and mechano-sensitive pathway, is downregulated in response to mechanical loading. Sclerostin neutralizing antibody (SclAb) increases bone formation. Nevertheless, it remains unclear whether sclerostin inhibition can rescue bone healing in situations of mechanical instability, which otherwise delay healing. We investigated SclAb's influence on tissue formation in a mouse femoral osteotomy, stabilized with Rigid or Semi-rigid external fixation...
April 25, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
D Bravo, A M Josephson, V Bradaschia-Correa, M Z Wong, N L Yim, S S Neibart, S N Lee, J Huo, T Coughlin, M M Mizrahi, P Leucht
INTRODUCTION: Aminocaproic acid is approved as an anti-fibrinolytic for use in joint replacement and spinal fusion surgeries to limit perioperative blood loss. Previous animal studies have demonstrated a pro-osteogenic effect of aminocaproic acid in spine fusion models. Here, we tested if aminocaproic acid enhances appendicular bone healing and we sought to uncover the effect of aminocaproic acid on osteoprogenitor cells (OPCs) during bone regeneration. METHODS: We employed a well-established murine femur fracture model in adult C57BL/6J mice after receiving two peri-operative injections of aminocaproic acid...
April 19, 2018: Bone
Kiyohisa Ogawa, Wataru Inokuchi
Osteochondroma (OC) is the most common benign bone tumor and may occur on any bone in which endochondral ossification develops. Although scapular OC accounts for less than 5% of the cases of solitary OC, OC is the most common lesion among the tumors and tumor-like lesions of the scapula. OC that develops near the medial scapular border easily causes friction with the ribcage; hence, almost half the number of cases of OC associated with marked bursa formation develops in the ventral scapula. We report a case of a 27-year-old female with a painful OC of the ventral scapular surface associated with large bursa formation and pseudowinging of the scapula...
2018: Case Reports in Orthopedics
Paola Occhetta, Sebastien Pigeot, Marco Rasponi, Boris Dasen, Arne Mehrkens, Thomas Ullrich, Ina Kramer, Sabine Guth-Gundel, Andrea Barbero, Ivan Martin
It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to generate phenotypically stable cartilage, it is questioned whether there is a correspondence between mesenchymal progenitor compartments during development and in adulthood. Here we tested whether forcing specific early events of articular cartilage development can program hMSC fate toward stable chondrogenesis...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Minami Fuse, Kazuhiko Sawada
The baculum (or os penis) is the non-appendicular osseous tissue owned by nine orders of mammals. In rodents, the baculum consists of three segments derived from developmentally-distinct origins: proximal endochondral, central intramembranous and distal cartilaginous segments (Murakami and Mizuno 1984). This report attempted to assess a contribution of physiological levels of prenatal testosterone to the mouse baculal morphology.
April 17, 2018: Congenital Anomalies
Mylène Tajan, Julie Pernin-Grandjean, Nicolas Beton, Isabelle Gennero, Florence Capilla, Benjamin G Neel, Toshiyuki Araki, Philippe Valet, Maithé Tauber, Jean-Pierre Salles, Armelle Yart, Thomas Edouard
Growth retardation is a constant feature of Noonan syndrome (NS) but its physiopathology remains poorly understood. We previously reported that hyperactive NS-causing SHP2 mutants impair the systemic production of insulin-like growth factor 1 (IGF1) through hyperactivation of the RAS/extracellular signal-regulated kinases (ERK) signalling pathway. Besides endocrine defects, a direct effect of these mutants on growth plate has not been explored, although recent studies have revealed an important physiological role for SHP2 in endochondral bone growth...
April 12, 2018: Human Molecular Genetics
Tina Histing, Philipp Bremer, Mika F Rollmann, Steven Herath, Moritz Klein, Tim Pohlemann, Michael D Menger, Tobias Fritz
Bone healing models are necessary to analyze the complex mechanisms of fracture healing to improve clinical fracture treatment. During the last decade, an increased use of mouse models in orthopedic research was noted, most probably because mouse models offer a large number of genetically-modified strains and special antibodies for the analysis of molecular mechanisms of fracture healing. To control the biomechanical conditions, well-characterized osteosynthesis techniques are mandatory, also in mice. Here, we report on the design and use of a closed bone healing model to stabilize femur fractures in mice...
March 22, 2018: Journal of Visualized Experiments: JoVE
Vishal Mohanakrishnan, Arumugam Balasubramanian, Gokulnath Mahalingam, Nicola Chennell Partridge, Ilangovan Ramachandran, Nagarajan Selvamurugan
Parathyroid hormone (PTH) acts on osteoblasts and functions as an essential regulator of calcium homeostasis and as a mediator of bone remodeling. We previously reported that PTH stimulates the expression of matrix metalloproteinase-13 (MMP-13) in rat osteoblasts and that MMP-13 plays a key role in bone remodeling, endochondral bone formation, and bone repair. Recent evidence indicated that microRNAs (miRNAs) have regulatory functions in bone metabolism. In this study, we hypothesized that the down-regulation of miRNAs that target MMP-13 by PTH leads to the stimulation of MMP-13 expression in osteoblasts...
April 6, 2018: Journal of Cellular Biochemistry
Julian Schuelke, Nicholaus Meyers, Sandra Reitmaier, Svenja Klose, Anita Ignatius, Lutz Claes
The mechanical environment is a primary factor in the success of distraction osteogenesis. It is known that the interfragmentary movement during the distraction and maturation phase effects the callus formation. In addition to cyclic compression, other movements like shear and bending influence the bone formation process as shown in previous callus distraction studies. Reports of cartilage presence and endochondral ossification in the regenerative zone have been associated with a lack of fixation stability and delayed healing...
2018: PloS One
Qingfeng Ding, Peng Sun, Hao Zhou, Bowen Wan, Jian Yin, Yao Huang, Qingqing Li, Guoyong Yin, Jin Fan
Intermittent low‑dose injections of parathyroid hormone (PTH) have been reported to exert bone anabolic effects and to promote fracture healing. As an important proangiogenic cytokine, vascular endothelial growth factor (VEGF) is secreted by bone marrow mesenchymal stem cells (BMSCs) and osteoblasts, and serves a crucial regulatory role in the process of vascular development and regeneration. To investigate whether lack of endogenous PTH causes reduced angiogenic capacity and thereby delays the process of fracture healing by downregulating the VEGF signaling pathway, a PTH knockout (PTHKO) mouse fracture model was generated...
April 3, 2018: International Journal of Molecular Medicine
Behzad Javaheri, Soraia P Caetano-Silva, Ioannis Kanakis, George Bou-Gharios, Andrew A Pitsillides
Endochondral ossification (EO), by which long bones of the axial skeleton form, is a tightly regulated process involving chondrocyte maturation with successive stages of proliferation, maturation, and hypertrophy, accompanied by cartilage matrix synthesis, calcification, and angiogenesis, followed by osteoblast-mediated ossification. This developmental sequence reappears during fracture repair and in osteoarthritic etiopathology. These similarities suggest that EO, and the cells involved, are of great clinical importance for bone regeneration as it could provide novel targeted approaches to increase specific signaling to promote fracture healing, and if regulated appropriately in the treatment of osteoarthritis...
2018: Frontiers in Bioengineering and Biotechnology
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