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https://www.readbyqxmd.com/read/28319320/the-endochondral-bone-protein-chm1-sustains-an-undifferentiated-invasive-phenotype-promoting-lung-metastasis-in-ewing-sarcoma
#1
Kristina von Heyking, Julia Calzada-Wack, Stefanie Göllner, Frauke Neff, Oxana Schmidt, Tim Hensel, David Schirmer, Annette Fasan, Irene Esposito, Carsten Müller-Tidow, Poul H Sorensen, Stefan Burdach, Günther H S Richter
Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by EWS-ETS translocations and early metastasis to lung and bone. In this study, we investigated the role of the BRICHOS chaperone domain-containing endochondral bone protein chondromodulin I (CHM1) in ES pathogenesis. CHM1 is significantly over-expressed in ES, and chromosome immunoprecipitation (ChIP) data demonstrate CHM1 to be directly bound by an EWS-ETS translocation, EWS-FLI1. Using RNA interference we observed that CHM1 promoted chondrogenic differentiation capacity of ES cells but decreased the expression of osteolytic genes such as HIF1A, IL6, JAG1 and VEGF...
March 20, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28304100/cartilage-specific-autophagy-deficiency-promotes-er-stress-and-impairs-chondrogenesis-in-perk-atf4-chop-dependent-manner
#2
Xiaomin Kang, Wei Yang, Dongxu Feng, Xinxin Jin, Zhengmin Ma, Zhuang Qian, Tianping Xie, Huixia Li, Jiali Liu, Ruiqi Wang, Fang Li, Danhui Li, Hongzhi Sun, Shufang Wu
Autophagy is activated during nutritionally depleted or hypoxic conditions to facilitate cell survival. As growth plate is an avascular and hypoxic tissue, autophagy may have a crucial role during chondrogenesis, however the functional role and underlying mechanism of autophagy in regulation of growth plate remains elusive. In this study, we generated (TamCart) Atg7(-/-) (Atg7cKO) mice to explore the role of autophagy during endochondral ossification. Atg7cKO mice exhibited growth retardation associated with reduced chondrocyte proliferation, differentiation and increased chondrocyte apoptosis...
March 17, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28290981/case-report-of-clinical-vignette-osteopetrosis
#3
John B Moore, Thanh D Hoang, Alfred F Shwayhat
INTRODUCTION: Osteopetrosis is a connective tissue disorder resulting from abnormally dense bone predisposing patients to fracture. The clinical pattern of fractures across time and space as well as suggestive radiographic findings usually raises diagnostic suspicion. Multiple genetic mutations resulting in dysfunctional osteoclasts have been implicated in the pathogenesis of osteopetrosis with variable inheritance patterns. In severe cases, usually inherited in an autosomal recessive pattern, the medullary cavity important in the production of normal blood cell progenitors is replaced by defective endochondral bone, leading to pancytopenia and consequential extramedullary hematopoiesis...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28285015/tnf%C3%AE-contributes-to-diabetes-impaired-angiogenesis-in-fracture-healing
#4
Jason C Lim, Kang I Ko, Marcelo Mattos, Miao Fang, Citong Zhang, Daniel Feinberg, Hisham Sindi, Shuai Li, Jazia Alblowi, Rayyan A Kayal, Thomas A Einhorn, Louis Gerstenfeld, Dana Graves
Diabetes increases the likelihood of fracture, interferes with fracture healing and impairs angiogenesis. The latter may be significant due to the critical nature of angiogenesis in fracture healing. Although it is known that diabetes interferes with angiogenesis the mechanisms remain poorly defined. We examined fracture healing in normoglycemic and streptozotocin-induced diabetic mice and quantified the degree of angiogenesis with antibodies to three different vascular markers, CD34, CD31 and Factor VIII. The role of diabetes-enhanced inflammation was investigated by treatment of the TNFα-specific inhibitor, pegsunercept starting 10days after induction of fractures...
March 8, 2017: Bone
https://www.readbyqxmd.com/read/28284715/hyaluronan-binding-protein-involved-in-hyaluronan-depolymerization-controls-endochondral-ossification-through-hyaluronan-metabolism
#5
Masayuki Shimoda, Hiroyuki Yoshida, Sakiko Mizuno, Toru Hirozane, Keisuke Horiuchi, Yuta Yoshino, Hideaki Hara, Yae Kanai, Shintaro Inoue, Muneaki Ishijima, Yasunori Okada
Hyaluronan (HA) plays an important role in the development and maintenance of tissues, and its degradation is implicated in many pathologic conditions. We recently reported that HA-binding protein involved in HA depolymerization (HYBID/KIAA1199; encoded by CEMIP) is a key molecule in HA depolymerization, but its developmental and pathologic functions remain elusive. We generated Hybid-deficient mice using the Cre/locus of crossover in P1 (loxP) system and analyzed their phenotypes. Hybid-deficient mice were viable and fertile, but their adult long bones were shorter than those of wild-type animals...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28282242/influence-of-the-injury-to-surgery-interval-on-the-healing-potential-of-human-anterior-cruciate-ligament-derived-cells
#6
Takao Inokuchi, Tomoyuki Matsumoto, Koji Takayama, Naoki Nakano, Shurong Zhang, Daisuke Araki, Takehiko Matsushita, Ryosuke Kuroda
BACKGROUND: Vascular CD34+ cells in anterior cruciate ligament (ACL) tissue have the potential for high proliferation and multilineage differentiation that can accelerate tendon-bone healing. While patient characteristics, such as age, can affect tendon-bone healing, the influence of elapsed time after injury on the healing process is unclear. HYPOTHESIS: Cells obtained during the early phase after injury will exhibit a greater tendon-bone healing potential compared with chronic phase counterparts when applied to an immunodeficient rat model of ACL reconstruction...
March 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28257738/atorvastatin-induced-osteoclast-inhibition-reduces-orthodontic-relapse
#7
Gabriel Schmidt Dolci, Luis Valmor Portela, Diogo Onofre de Souza, Anna Christina Medeiros Fossati
INTRODUCTION: The statin class of drugs enhances osteogenesis and suppresses bone resorption, which could be a plausible biologic mechanism for mitigation of orthodontic relapse. We aimed to determine whether atorvastatin (ATV) might affect orthodontic relapse and osteoclastogenesis by modulating expression of RANKL and osteoprotegerin (OPG), crucial molecules involved in bone turnover. Furthermore, we analyzed the adverse effects of ATV on femur turnover and endochondral ossification...
March 2017: American Journal of Orthodontics and Dentofacial Orthopedics
https://www.readbyqxmd.com/read/28250250/establishment-of-heterotopic-ossification-via-sharp-instrument-injury-in-rats
#8
J-C Xu, G-H Wu, L-L Zhou, X-J Yang, J-T Liu
OBJECTIVE: To establish an animal model for heterotopic ossification (HO) induced by sharp instrument injury in Sprague-Dawley (SD) rat and to investigate its possible mechanism. MATERIALS AND METHODS: A total of 48 male SD rats were divided into 3 groups (n=16). In sham group, incision and suture were performed only in the left leg. Partial tenotomy was performed in the left Achilles tendons in the PAT group. In Achilles' tenotomy (AT) group, tenotomy was performed in the left Achilles tendons to establish animal model of EO...
March 1, 2017: Journal of Musculoskeletal & Neuronal Interactions
https://www.readbyqxmd.com/read/28220293/effects-of-bisphosphonates-on-osteogenesis-and-osteoclastogenesis-signaling-during-the-endochondral-ossification-of-growing-rats
#9
Eloiza Rezende, Vivian Bradaschia-Correa, Fabio Siviero, Lucas M B Ambrosio, Victor E Arana-Chavez
Osteoclasts and chondroclasts are necessary, during endochondral ossification, for the resorption of primary bone and calcified cartilage septa, respectively. The bisphosphonates inhibit mineralized tissue resorption by various mechanisms according to the different types of this drug, which can affect bone remodeling during skeletal growth. The objective of the present study is to analyze the way that alendronate (ALN) and etidronate (ETN) can affect osteoclastogenesis and bone formation during endochondral ossification of the long bones of growing rats...
February 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28218908/cell-matrix-signals-specify-bone-endothelial-cells-during-developmental-osteogenesis
#10
Urs H Langen, Mara E Pitulescu, Jung Mo Kim, Rocio Enriquez-Gasca, Kishor K Sivaraj, Anjali P Kusumbe, Amit Singh, Jacopo Di Russo, M Gabriele Bixel, Bin Zhou, Lydia Sorokin, Juan M Vaquerizas, Ralf H Adams
Blood vessels in the mammalian skeletal system control bone formation and support haematopoiesis by generating local niche environments. While a specialized capillary subtype, termed type H, has been recently shown to couple angiogenesis and osteogenesis in adolescent, adult and ageing mice, little is known about the formation of specific endothelial cell populations during early developmental endochondral bone formation. Here, we report that embryonic and early postnatal long bone contains a specialized endothelial cell subtype, termed type E, which strongly supports osteoblast lineage cells and later gives rise to other endothelial cell subpopulations...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28217849/how-long-bones-grow-children-mechanistic-paths-to-variation-in-human-height-growth
#11
REVIEW
Michelle Lampl, Meriah Schoen
OBJECTIVES: Eveleth and Tanner's descriptive documentation of worldwide variability in human growth provided evidence of the interaction between genetics and environment during development that has been foundational to the science of human growth. There remains a need, however, to describe the mechanistic foundations of variability in human height growth patterns. METHODS: A review of research documenting cellular activities at the endochondral growth plate aims to show how the unique microenvironment and cell functions during the sequential phases of the chondrocyte lifecycle affect long bone elongation, a fundamental source of height growth...
February 20, 2017: American Journal of Human Biology: the Official Journal of the Human Biology Council
https://www.readbyqxmd.com/read/28197989/growth-plate-extracellular-matrix-derived-scaffolds-for-large-bone-defect-healing
#12
G M Cunniffe, P J Díaz-Payno, J S Ramey, O R Mahon, A Dunne, E M Thompson, F J O'Brien, D J Kelly
Limitations associated with demineralised bone matrix and other grafting materials have motivated the development of alternative strategies to enhance the repair of large bone defects. The growth plate (GP) of developing limbs contain a plethora of growth factors and matrix cues which contribute to long bone growth, suggesting that biomaterials derived from its extracellular matrix (ECM) may be uniquely suited to promoting bone regeneration. The goal of this study was to generate porous scaffolds from decellularised GP ECM and to evaluate their ability to enhance host mediated bone regeneration following their implantation into critically-sized rat cranial defects...
February 14, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/28196691/healing-of-a-large-long-bone-defect-through-serum-free-in%C3%A2-vitro-priming-of%C3%A2-human-periosteum-derived-cells
#13
Johanna Bolander, Wei Ji, Jeroen Leijten, Liliana Moreira Teixeira, Veerle Bloemen, Dennis Lambrechts, Malay Chaklader, Frank P Luyten
Clinical translation of cell-based strategies for regenerative medicine demands predictable in vivo performance where the use of sera during in vitro preparation inherently limits the efficacy and reproducibility. Here, we present a bioinspired approach by serum-free pre-conditioning of human periosteum-derived cells, followed by their assembly into microaggregates simultaneously primed with bone morphogenetic protein 2 (BMP-2). Pre-conditioning resulted in a more potent progenitor cell population, while aggregation induced osteochondrogenic differentiation, further enhanced by BMP-2 stimulation...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28191761/angiogenic-potential-of-human-bone-marrow-derived-mesenchymal-stem-cells-in-chondrocyte-brick-enriched-constructs-promoted-stable-regeneration-of-craniofacial-cartilage
#14
Zhiye Li, Ruikai Ba, Zhifa Wang, Jianhua Wei, Yimin Zhao, Wei Wu
Craniofacial deformities caused by congenital defects or trauma remain challenges for clinicians, whereas current surgical interventions present limited therapeutic outcomes. Injection of bone marrow-derived mesenchymal stem cells (BMSCs) into the defect is highly desirable because such a procedure is microinvasive and grafts are more flexible to fill the lesions. However, preventing hypertrophic transition and morphological contraction remain significant challenges. We have developed an "all host derived" cell transplantation system composed of chondrocyte brick (CB)-enriched platelet-rich plasma (P) gel and BMSCs (B)...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28186356/bone-robusticity-in-two-distinct-skeletal-dysplasias-diverges-from-established-patterns
#15
Kate Citron, Cosmo Veneziale, Josephine Marino, Erin M Carter, Karl J Jepsen, Cathleen Raggio
Achondroplasia is a heritable disorder of endochondral bone formation characterized by disproportionate short stature. Osteogenesis imperfecta is a heritable bone and connective tissue disorder characterized by bone fragility. To investigate bone morphology of these groups, we retrospectively reviewed 169 de-identified bone age films from 20 individuals with achondroplasia, 39 individuals with osteogenesis imperfecta and 37 age- and sex-matched controls (matched to historical measurements from the Bolton-Brush Collection)...
February 10, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28178186/exogenous-pthrp-repairs-the-damaged-fracture-healing-of-pthrp-mice-and-accelerates-fracture-healing-of-wild-mice
#16
Yinhe Wang, Xin Fang, Chun Wang, Congzhu Ding, Hua Lin, Anlong Liu, Lei Wang, Yang Cao
Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone-related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/- mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods...
February 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28166224/mesoderm-specific-stat3-deletion-affects-expression-of-sox9-yielding-sox9-dependent-phenotypes
#17
Michael D Hall, Caroline A Murray, Michael J Valdez, Alan O Perantoni
To date, mutations within the coding region and translocations around the SOX9 gene both constitute the majority of genetic lesions underpinning human campomelic dysplasia (CD). While pathological coding-region mutations typically result in a non-functional SOX9 protein, little is known about what mechanism(s) controls normal SOX9 expression, and subsequently, which signaling pathways may be interrupted by alterations occurring around the SOX9 gene. Here, we report the identification of Stat3 as a key modulator of Sox9 expression in nascent cartilage and developing chondrocytes...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28164198/sialoglycoprotein-isolated-from-the-eggs-of-gadus-morhua-enhances-fracture-healing-in-osteoporotic-mice
#18
Qiping Zhan, Xiong Gui, Fei Wang, Peng Yu, Meihui Zhao, Jingfeng Wang, Changhu Xue
Osteoporosis is a common disease in the elderly, which is related to fracture healing delay. In this study, the effects of treatment with sialoglycoprotein isolated from the eggs of Gadus morhua (Gm-SGP) on tibial fracture healing in ovariectomized (OVX) osteoporotic female C57BL/6J mice for 56 days post-fracture were investigated. The result showed that Gm-SGP treatment significantly increased serum angiogenic factors and bone formation markers on day 5 and 11 post-fracture when compared with the OVX group...
February 6, 2017: Food & Function
https://www.readbyqxmd.com/read/28148490/characterisation-of-osteophytes-as-an-autologous-bone-graft-source-an-experimental-study-in-vivo-and-in-vitro
#19
K Ishihara, K Okazaki, T Akiyama, Y Akasaki, Y Nakashima
OBJECTIVES: Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. METHODS: Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation...
February 2017: Bone & Joint Research
https://www.readbyqxmd.com/read/28145573/static-osteogenesis-does-not-precede-dynamic-osteogenesis-in-periosteal-ossification-of-pleurodeles-caudata-amphibia-and-pogona-squamata-lepidosauria
#20
Jorge Cubo, Mylaine Hui, François Clarac, Alexandra Quilhac
Two successive mechanisms have been described in perichondral ossification: (1) in static osteogenesis, mesenchymal cells differentiate into stationary osteoblasts oriented randomly, which differentiate into osteocytes in the same site; (2) in dynamic osteogenesis, mesenchymal cells differentiate into osteoblasts that are all oriented in the same direction and move back as they secrete collagen fibers. This study is aimed at testing the hypothesis that the ontogenetic sequence static then dynamic osteogenesis observed in the chicken and in the rabbit is homologous and was acquired by the last common ancestor of amniotes or at a more inclusive node...
February 1, 2017: Journal of Morphology
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