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https://www.readbyqxmd.com/read/28924384/fgfr3-deficient-mice-have-accelerated-fracture-repair
#1
Yangli Xie, Fengtao Luo, Wei Xu, Zuqiang Wang, Xianding Sun, Meng Xu, Junlan Huang, Dali Zhang, Qiaoyan Tan, Bo Chen, Wanling Jiang, Xiaolan Du, Lin Chen
Bone fracture healing is processed through multiple biological stages that partly recapitulates the skeletal development process. FGFR3 is a negative regulator of chondrogenesis during embryonic stage and plays an important role in both chondrogenesis and osteogenesis. We have investigated the role of FGFR3 in fracture healing using unstabilized fracture model and found that gain-of-function mutation of FGFR3 inhibits the initiation of chondrogenesis during cartilage callus formation. Here, we created closed, stabilized proximal tibia fractures with an intramedullary pin in Fgfr3(-/-)mice and their littermate wild-type mice...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28913932/hox-d-genes-and-the-fin-to-limb-transition-insights-from-fish-studies
#2
REVIEW
Ana Paço, Renata Freitas
Genes in the 5' extremity of the HoxD cluster encode DNA-binding transcription factors essential for development of the autopod and digits, regulating primarily gene expression and, consequently, morphogenesis and skeletal differentiation. Comparative studies focused on their expression and regulation have led to the idea that evolution of a bimodal regulation of the HoxD cluster, mainly due to the activation of cis-regulatory units in the centromeric side of the cluster, was a fundamental mechanism that potentiated the fin-to-limb transition in vertebrates...
September 14, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28902741/the-influence-of-geography-time-and-payer-type-on-the-utilization-of-bone-morphogenetic-protein-bmp-between-2005-and-2015
#3
Sohrab S Virk, Frank M Phillips, Safdar N Khan
Bone morphogenetic protein (BMP) is a critical compound for endochondral bone formation and is used as a bone graft substitute to promote spinal fusion and fracture healing. We sought to identify rate, type, and applications of use of BMP in spinal fusion surgery during 2005 to 2015. The Medicare 5% national sample (SAF5) database and the Humana Orthopaedics database (HORTHO) were searched for patients who underwent spinal fusion with BMP. Rate of use over time and influence of geographic region and payer type on utilization of BMP during 2005 to 2015 were analyzed...
September 11, 2017: Clinical Spine Surgery
https://www.readbyqxmd.com/read/28901584/the-primary-cilium-as-a-signaling-nexus-for-growth-plate-function-and-subsequent-skeletal-development
#4
REVIEW
Emily R Moore, Christopher R Jacobs
The primary cilium is a solitary, antenna-like sensory organelle with many important roles in cartilage and bone development, maintenance, and function. The primary cilium's potential role as a signaling nexus in the growth plate makes it an attractive therapeutic target for diseases and disorders associated with bone development and maintenance. Many signaling pathways that are mediated by the cilium - such as Hh, Wnt, Ihh/PTHrP, TGFβ, BMP, FGF, and Notch - are also known to influence endochondral ossification, primarily by directing growth plate formation and chondrocyte behavior...
September 13, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28899838/design-and-evaluation-of-novel-natriuretic-peptide-derivatives-with-improved-pharmacokinetic-and-pharmacodynamic-properties
#5
Naomi Morozumi, Seiji Sato, Sayaka Yoshida, Yuriko Harada, Mayumi Furuya, Yoshiharu Minamitake, Kenji Kangawa
C-type natriuretic peptide (CNP) and its receptor, natriuretic peptide receptor B (NPR-B), are potent positive regulators of endochondral bone growth, making the CNP pathway one of the most promising therapeutic targets for the treatment of growth failure. However, the administration of exogenous CNP is not fully effective, due to its rapid clearance in vivo. Modification of CNP to potentially druggable derivatives may result in increased resistance to proteolytic degradation, longer plasma half-life (T1/2), and better distribution to target tissues...
September 9, 2017: Peptides
https://www.readbyqxmd.com/read/28879048/no-evidence-for-a-direct-role-of-hla-b27-in-pathological-bone-formation-in-axial-spa
#6
Barbara Neerinckx, Simon Kollnberger, Jacqueline Shaw, Rik Lories
OBJECTIVE: The strong genetic association between HLA-B27 and ankylosing spondylitis has been known for over 40 years. HLA-B27 positivity is possibly associated with severity of ankylosis. We studied the in vitro and in vivo impact of HLA-B27 in models of chondrogenesis and osteogenesis. METHODS: Different in vitro differentiation systems were used to mimic endochondral and direct bone formation. ATDC5 cells and primary human periosteum-derived cells (hPDCs) were transduced with lentiviral vectors expressing HLA-B27 or HLA-B7...
2017: RMD Open
https://www.readbyqxmd.com/read/28874841/epiphyseal-bone-formation-occurs-via-thyroid-hormone-regulation-of-chondrocyte-to-osteoblast-transdifferentiation
#7
Patrick Aghajanian, Weirong Xing, Shaohong Cheng, Subburaman Mohan
Endochondral ossification in the diaphysis of long bones has been studied in-depth during fetal development but not postnatally in the epiphysis. Immunohistochemical studies revealed that Sox9 and Col2 expressing immature chondrocytes in the epiphysis transition into prehypertrophic and hypetrophic chondrocytes and finally into osteoblasts expressing Col1 and BSP during postnatal day 7-10, when serum levels of thyroid hormone (TH) rise. Lineage tracing using Rosa-td tomato (Col2-Cre-ERT2) mice treated with tamoxifen indicated that the same Col2 expressing chondrocytes expressed prehypertrophic, hypertrophic, and subsequently bone formation markers in a sequential manner in euthyroid but not hypothyroid mice, thus providing evidence that chondrocyte to osteoblast transdifferentiation is TH-dependent...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28869677/fibroblasts-derived-from-patients-with-opsismodysplasia-display-ship2-specific-cell-migration-and-adhesion-defects
#8
Somadri Ghosh, Céline Huber, Quentin Siour, Sergio S Sousa, Michael Wright, Valérie Cormier-Daire, Christophe Erneux
The SH2 domain containing inositol phosphatase 2 (SHIP2) dephosphorylates PI(3,4,5)P3 to generate PI(3,4)P2, a lipid involved in the control of cell migration and adhesion. The INPPL1 gene that encodes SHIP2 has been found to be mutated in several cases of opsismodysplasia (OPS), a rare autosomal recessive chondrodysplasia characterized by growth plate defects and delayed bone maturation. Reported mutations often result in premature stop codons or missense mutations in SHIP2 catalytic domain. SHIP2 biochemical properties are known from studies in cancer cells; its role in endochondral ossification is unknown...
September 4, 2017: Human Mutation
https://www.readbyqxmd.com/read/28862380/fetal-bone-marrow-derived-mesenchymal-stem-stromal-cells-enhance-humanization-and-bone-formation-of-bmp7-loaded-scaffolds
#9
Abbas Shafiee, Jeremy G Baldwin, Jatin Patel, Boris M Holzapfel, Nicholas M Fisk, Kiarash Khosrotehrani, Dietmar W Hutmacher
Tissue engineered constructs built with human cells capable of generating a bone-like organ within the mouse have attracted considerable interest over the past decade. Here, we aimed to compare the utility of human mesenchymal stem/stromal cells (MSC) isolated from fetal term placenta (fPL-MSC) and fetal first trimester bone marrow (fBM-MSC) in a polycaprolactone scaffold/BMP7-based model in nude mice. Furthermore, fPL-MSC were co-seeded with fetal placenta-derived endothelial colony forming cells (ECFC) to assess the impact of ECFC on fPL-MSC osteogenesis...
September 1, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28855706/chondrogenesis-and-osteogenesis-are-one-continuous-developmental-and-lineage-defined-biological-process
#10
Yan Jing, Junjun Jing, Ling Ye, Xiaohua Liu, Stephen E Harris, Robert J Hinton, Jian Q Feng
Although chondrogenesis and osteogenesis are considered as two separate processes during endochondral bone formation after birth, recent studies have demonstrated the direct cell transformation from chondrocytes into bone cells in postnatal bone growth. Here we use cell lineage tracing and multiple in vivo approaches to study the role of Bmpr1a in endochondrogenesis. Our data showed profound changes in skeletal shape, size and structure when Bmpr1a was deleted using Aggrecan-Cre (ERT2) in early cartilage cells with a one-time tamoxifen injection...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852989/biophysical-aspects-of-biomineralization
#11
REVIEW
Maytê Bolean, Ana M S Simão, Marina B Barioni, Bruno Z Favarin, Heitor G Sebinelli, Ekeveliny A Veschi, Tatiane A B Janku, Massimo Bottini, Marc F Hoylaerts, Rosangela Itri, José L Millán, Pietro Ciancaglini
During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix (ECM) by promoting the synthesis of hydroxyapatite (HA) seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Several lipid and proteins present in the membrane of the MVs mediate the interactions of MVs with the ECM and regulate the initial mineral deposition and posterior propagation. Among the proteins of MV membranes, ion transporters control the availability of phosphate and calcium needed for initial HA deposition...
August 29, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28826842/retinoid-roles-and-action-in-skeletal-development-and-growth-provide-the-rationale-for-an-ongoing-heterotopic-ossification-prevention-trial
#12
Maurizio Pacifici
The majority of skeletal elements develop via endochondral ossification. This process starts with formation of mesenchymal cell condensations at prescribed sites and times in the early embryo and is followed by chondrogenesis, growth plate cartilage maturation and hypertrophy, and replacement of cartilage with bone and marrow. This complex stepwise process is reactivated and recapitulated in physiologic conditions such as fracture repair, but can occur extraskeletally in pathologies including heterotopic ossification (HO), Ossification of the Posterior Longitudinal Ligament (OPLL) and Hereditary Multiple Exostoses (HME)...
August 18, 2017: Bone
https://www.readbyqxmd.com/read/28816826/tissue-engineered-bone-differentiated-from-human-adipose-derived-stem-cells-inhibit-posterolateral-fusion-in-an-athymic-rat-model
#13
Comron Saifi, Jonahtan Bernhard, Jamal N Shillingford, Petros Petridis, Samuel Robinson, X Edward Guo, Mark Weidenbaum, Ronald A Lehman, Howard S An, Lawrence G Lenke, Gordana Vunjak-Novakovic, Joseph L Laratta
STUDY DESIGN: Biological augmentation spinal arthrodesis trial in athymic rats OBJECTIVE.: To assess the efficacy of tissue-engineered bone to promote L4-L5 intertransverse process fusion in an athymic rat model. SUMMARY OF BACKGROUND DATA: Each year in the United States, over 400,000 spinal fusion surgeries are performed requiring bone graft. The current gold standard for posterolateral lumbar fusion is autogenous iliac crest bone graft (ICBG), but the harvesting of ICBG is associated with increased operative time and significant complications...
August 14, 2017: Spine
https://www.readbyqxmd.com/read/28816104/the-immune-response-to-allogeneic-differentiated-mesenchymal-stem-cells-in-the-context-of-bone-tissue-engineering
#14
Caoimhe H Kiernan, Eppo B Wolvius, Pieter A J Brama, Eric Farrell
The use of allogeneic differentiated mesenchymal stem cells (MSCs) to mediate bone formation may be a potential alternative to the current gold standards of bone repair. While it is known that undifferentiated MSCs are immunomodulatory and weakly immunogenic, the host immune reaction to differentiated MSCs is less known. Implantation of allogeneic osteogenic or chondrogenically differentiated MSC pellets may be promising routes to induce bone repair via the processes of intramembranous and endochondral ossification...
August 17, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28802681/activated-fgfr3-promotes-bone-formation-via-accelerating-endochondral-ossification-in-mouse-model-of-distraction-osteogenesis
#15
Yusuke Osawa, Masaki Matsushita, Sachi Hasegawa, Ryusaku Esaki, Masahito Fujio, Bisei Ohkawara, Naoki Ishiguro, Kinji Ohno, Hiroshi Kitoh
Achondroplasia (ACH) is one of the most common short-limbed skeletal dysplasias caused by gain-of-function mutations in the fibroblast growth factor receptors 3 (FGFR3) gene. Distraction osteogenesis (DO) is a treatment option for short stature in ACH in some countries. Although the patients with ACH usually show faster healing in DO, details of the newly formed bone have not been examined. We have developed a mouse model of DO and analyzed new bone regenerates of the transgenic mice with ACH (Fgfr3(ach) mice) histologically and morphologically...
August 10, 2017: Bone
https://www.readbyqxmd.com/read/28798933/tumor-proteins-d52-and-d54-have-opposite-effects-on-the-terminal-differentiation-of-chondrocytes
#16
Chihiro Ito, Yoshiki Mukudai, Masakatsu Itose, Kosuke Kato, Hiromi Motohashi, Toshikazu Shimane, Seiji Kondo, Tatsuo Shirota
The tumor protein D (TPD) family consists of four members, TPD52, TPD53, TPD54, and TPD55. The physiological roles of these genes in normal tissues, including epidermal and mesenchymal tissues, have rarely been reported. Herein, we examined the expression of TPD52 and TPD54 genes in cartilage in vivo and in vitro and investigated their involvement in the proliferation and differentiation of chondrocytes in vitro. TPD52 and TPD54 were uniformly expressed in articular cartilage and trabecular bone and were scarcely expressed in the epiphyseal growth plate...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28798204/imaging-igf-i-uptake-in-growth-plate-cartilage-using-in-vivo-multiphoton-microscopy
#17
Maria A Serrat, Gabriela Ion
Bones elongate through endochondral ossification in cartilaginous growth plates located at ends of primary long bones. Linear growth ensues from a cascade of biochemical signals initiated by actions of systemic and local regulators on growth plate chondrocytes. Although cellular processes are well defined, there is a fundamental gap in understanding how growth regulators are physically transported from surrounding blood vessels into and through dense, avascular cartilage matrix. Intravital imaging using in vivo multiphoton microscopy is one promising strategy to overcome this barrier by quantitatively tracking molecular delivery to cartilage from the vasculature in real time...
August 10, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28782836/histone-deacetylase-3-deletion-in-mesenchymal-progenitor-cells-hinders-long-bone-development
#18
Marina Feigenson, Lomeli Carpio Shull, Earnest L Taylor, Emily T Camilleri, Scott M Riester, Andre J van Wijnen, Elizabeth W Bradley, Jennifer J Westendorf
Long bone formation is a complex process that requires precise transcriptional control of gene expression programs in mesenchymal progenitor cells. Histone deacetylases (Hdacs) coordinate chromatin structure and gene expression by enzymatically removing acetyl groups from histones and other proteins. Hdac inhibitors are used clinically to manage mood disorders, cancers, and other conditions but are teratogenic to the developing skeleton and increase fracture risk in adults. In this study, the functions of Hdac3, one of the enzymes blocked by current Hdac inhibitor therapies, in skeletal mesenchymal progenitor cells were determined...
August 7, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28758906/activin-a-enhances-mtor-signaling-to-promote-aberrant-chondrogenesis-in-fibrodysplasia-ossificans-progressiva
#19
Kyosuke Hino, Kazuhiko Horigome, Megumi Nishio, Shingo Komura, Sanae Nagata, Chengzhu Zhao, Yonghui Jin, Koichi Kawakami, Yasuhiro Yamada, Akira Ohta, Junya Toguchida, Makoto Ikeya
Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Although Activin-A evokes enhanced chondrogenesis in vitro and heterotopic ossification (HO) in vivo, the underlying mechanisms have yet to be revealed...
September 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28756737/mimicking-the-biochemical-and-mechanical-extracellular-environment-of-the-endochondral-ossification-process-to-enhance-the-in-vitro-mineralization-potential-of-human-mscs
#20
Fiona E Freeman, Jessica Schiavi, Meadhbh A Brennan, Peter Owens, Pierre Layrolle, Laoise McNamara
Chondrogenesis and mechanical stimulation of the cartilage template, are essential for bone formation via the endochondral ossification process in vivo. Recent studies have demonstrated that in vitro regeneration strategies that mimic these aspects separately, either chondrogenesis or mechanical stimulation, can promote mineralization to a certain extent both in vitro and in vivo. However, to date no study has sought to incorporate both the formation of the cartilage template and the application of mechanical stimulation simultaneously to induce osteogenesis...
July 29, 2017: Tissue Engineering. Part A
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