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endochondral bone

Katie Bardsley, Agnieska Kwarciak, Christine Freeman, Ian Brook, Paul Hatton, Aileen Crawford
The regeneration of large bone defects remains clinically challenging. The aim of our study was to use a rat model to use nasal chondrocytes to engineer a hypertrophic cartilage tissue which could be remodelled into bone in vivo by endochondral ossification. Primary adult rat nasal chondrocytes were isolated from the nasal septum, the cell numbers expanded in monolayer culture and the cells cultured in vitro on polyglycolic acid scaffolds in chondrogenic medium for culture periods of 5-10 weeks. Hypertrophic differentiation was assessed by determining the temporal expression of key marker genes and proteins involved in hypertrophic cartilage formation...
October 11, 2016: Biomaterials
Anurati Saha, Rebecca Rolfe, Simon Carroll, Daniel J Kelly, Paula Murphy
Chondrogenesis in vivo is precisely controlled in time and space. The entire limb skeleton forms from cells at the core of the early limb bud that condense and undergo chondrogenic differentiation. Whether they form stable cartilage at the articular surface of the joint or transient cartilage that progresses to hypertrophy as endochondral bone, replacing the cartilage template of the skeletal rudiment, is spatially controlled over several days in the embryo. Here, we follow the differentiation of cells taken from the early limb bud (embryonic day 11...
October 22, 2016: Cell and Tissue Research
Fiona E Freeman, Laoise McNamara
Tissue engineering and regenerative medicine have significant potential to treat bone pathologies by exploiting the capacity for bone progenitors to grow and produce tissue constituents under specific biochemical and physical conditions. However, conventional tissue engineering approaches, which combine stem cells with biomaterial scaffolds, are limited as the constructs often degrade, due to a lack of vascularisation, and lack the mechanical integrity to fulfil loading bearing functions, and as such are not yet widely used for clinical treatment of large bone defects...
October 19, 2016: Tissue Engineering. Part B, Reviews
Kai Hu, Bjorn R Olsen
Vascular Endothelial Growth factor A (VEGF) is a critical regulator of vascular development, postnatal angiogenesis and homeostasis, and it is essential for bone development and repair. Blood vessels serve both as structural templates for bone formation and they provide essential cells, growth factors and minerals needed for synthesis and mineralization, as well as turnover, of the extracellular matrix in bone. Through its regulation of angiogenesis, VEGF contributes to coupling of osteogenesis to angiogenesis, and it directly controls the differentiation and function of osteoblasts and osteoclasts...
October 17, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Garyfallia Papaioannou, Fatemeh Mirzamohammadi, Tatsuya Kobayashi
During endochondral bone development, osteoblasts are continuously differentiated from locally residing progenitor cells. However, the regulation of such endogenous osteoprogenitor cells is still poorly understood mainly due to the difficulty in identifying such cells in vivo. In this paper, we genetically labeled different cell populations of the osteoblast linage using stage-specific, tamoxifen-inducible Cre transgenic mice to investigate their responses to a proliferative stimulus. We have found that overactivation of Kras signaling in type II collagen-positive, immature osteoprogenitor cells, but not in mature osteoblasts, substantially increases the number of their descendant stromal cells and mature osteoblasts, and subsequently increases bone mass...
October 13, 2016: Cell Death & Disease
Takako Hattori, Shinsuke Itoh, Masaharu Takigawa
Recent progress in gene-editing technology has provided a strong impact for improved our understanding of molecular functions in living organisms. Here we describe our method to generate transgene-overexpressing mouse models, which method involves the use of tissue-specific promoters for analyzing a certain molecule (s) in special tissues. The protocol described in this chapter uses the Col2a1 promoter-enhancer, which is known for driving specific and strong transgene expression in cartilage and is based on several of our studies showing a positive role of the connective tissue growth factor (CCN2) in cartilage-bone development and maintenance of articular cartilage...
2017: Methods in Molecular Biology
Connie Y Chang, Daniel I Rosenthal, Deborah M Mitchell, Atsuhiko Handa, Susan V Kattapuram, Ambrose J Huang
Metabolic bone diseases are a diverse group of diseases that result in abnormalities of (a) bone mass, (b) structure mineral homeostasis, (c) bone turnover, or (d) growth. Osteoporosis, the most common metabolic bone disease, results in generalized loss of bone mass and deterioration in the bone microarchitecture. Impaired chondrocyte development and failure to mineralize growth plate cartilage in rickets lead to widened growth plates and frayed metaphyses at sites of greatest growth. Osteomalacia is the result of impaired mineralization of newly formed osteoid, which leads to characteristic Looser zones...
October 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Murong You, Juehua Jing, Dasheng Tian, Jun Qian, Guangrong Yu
Dioscin has been shown to play important roles in suppression of osteoclast maturation. It is proposed as a potential natural product for the treatment of osteoclast-related diseases. We hypothesized in this study that treatment of dioscin on bone marrow mesenchymal stem cells (BMSCs) could increase the osteo-chondrogenic differentiation of BMSCs and promote endochondral ossification of BMSCs in bone fracture environment. BMSCs were extracted from femur and tibia of male C57b mice. Stemness of BMSCs was studied by performing proliferation assay and multilineage differentiation...
2016: American Journal of Translational Research
Adam O'Reilly, Daniel John Kelly
Developing successful tissue engineering strategies requires an understanding of how cells within an implanted scaffold interacts with the host environment. The objective of this study was to use a computational mechanobiological model to explore how the design of a cell laden scaffold influences the spatial formation of cartilage and bone within an osteochondral defect. Tissue differentiation was predicted using a previously developed model in which cell fate depends on the local oxygen tension and the mechanical environment within a damaged joint...
October 6, 2016: Tissue Engineering. Part A
Soonchul Lee, Jia Shen, Hsin Chuan Pan, Swati Shrestha, Greg Asatrian, Alan Nguyen, Carolyn Meyers, Vi Nguyen, Min Lee, Chia Soo, Kang Ting, Aaron W James
Hedgehog (Hh) signaling positively regulates both endochondral and intramembranous ossification. Use of small molecules for tissue engineering applications pose several advantages. Here, we examined whether use of an acellular scaffold treated with the small molecule Smoothened agonist (SAG) could aid in critical size mouse calvarial defect repair. First, we verified the pro-osteogenic effect of SAG in vitro, using primary neonatal mouse calvarial cells (NMCCs). Next, a 4 mm non-healing defect was created in the mid-parietal bone of ten week old CD-1 mice...
October 5, 2016: Tissue Engineering. Part A
Esperanza Macarena López-Pliego, Miguel Ángel Giráldez-Sánchez, Juan Mora-Macías, Esther Reina-Romo, Jaime Domínguez
INTRODUCTION: Bone transport (BT) for segmentary bone defects is a well-known technique as it enables correction with new bone formation, which is similar to the previous bone. Despite the high number of experimental studies of distraction osteogenesis in bone lengthening, the types of ossification and histological changes that occur in the regenerate of the bone transport process remain controversial. OBJECTIVE: The aim of this study is to provide the complete evolution of tissues and the types of ossification in the regenerate during the different phases of bone formation after BT until the end of the remodelling period...
September 2016: Injury
Holly E Weiss-Bilka, Megan E McGann, Matthew J Meagher, Ryan K Roeder, Diane R Wagner
Key aspects of native endochondral bone development and fracture healing can be mimicked in mesenchymal stem cells (MSCs) through standard in vitro chondrogenic induction. Exploiting this phenomenon has recently emerged as an attractive technique to engineer bone tissue, however relatively little is known about the best conditions for doing so. The objective of this study was to compare the bone forming capacity and angiogenic induction of hypertrophic cell constructs containing human adipose-derived stem cells (hASCs) primed for chondrogenesis in two different culture systems: high-density pellets and alginate bead hydrogels...
September 30, 2016: Journal of Tissue Engineering and Regenerative Medicine
Anna Neve, Nicola Maruotti, Addolorata Corrado, Francesco Paolo Cantatore
Despite intensive research in spondyloarthritis pathogenesis, some important questions still remain unanswered, particularly concerning enthesis new bone formation. Several evidences suggest that it prevalently occurs by endochondral ossification, however it remains to identify factors that can induce and influence its initiation and progression. Recent progress, achieved in animal models and in vitro and genetic associations studies, has led us to hypothesize that several systemic factors (adipokines and gut hormones) and local factors (BMP and Wnt signalling) as well as angiogenesis and mechanical stress are involved...
September 29, 2016: Annals of Medicine
Arkady Rutkovskiy, Kåre-Olav Stensløkken, Ingvar Jarle Vaage
Ossification is a tightly regulated process, performed by specialized cells called osteoblasts. Dysregulation of this process may cause inadequate or excessive mineralization of bones or ectopic calcification, all of which have grave consequences for human health. Understanding osteoblast biology may help to treat diseases such as osteogenesis imperfecta, calcific heart valve disease, osteoporosis, and many others. Osteoblasts are bone-building cells of mesenchymal origin; they differentiate from mesenchymal progenitors, either directly or via an osteochondroprogenitor...
September 26, 2016: Medical Science Monitor Basic Research
R J Hinton, Y Jing, J Jing, J Q Feng
The formation of the mandibular condylar cartilage (MCC) and its subchondral bone is an important but understudied topic in dental research. The current concept regarding endochondral bone formation postulates that most hypertrophic chondrocytes undergo programmed cell death prior to bone formation. Under this paradigm, the MCC and its underlying bone are thought to result from 2 closely linked but separate processes: chondrogenesis and osteogenesis. However, recent investigations using cell lineage tracing techniques have demonstrated that many, perhaps the majority, of bone cells are derived via direct transformation from chondrocytes...
September 23, 2016: Journal of Dental Research
Kai Hu, Tatiana Y Besschetnova, Bjorn R Olsen
BMP2 is widely used for promotion of bone repair and regeneration. However, bone formation induced by BMP2 is quite variable. Bone forming progenitor cells in different locations appear to respond to BMP2 in different ways, and repair outcomes can vary as a consequence of modulating effects by other factors. In this study, we have examined the effects of VEGF on BMP2-induced repair of a cortical bone defect, a 1 mm diameter drill hole, in the proximal tibia of mice. Treatment of the defect with either a bolus of PBS or soluble VEGFR1 (sVEGFR1), a decoy receptor for VEGF, had the same effects on bone formation via intramembranous ossification in the defect and cartilage formation and injured periosteum, during the healing process...
September 7, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Debajyoti Chatterjee, Kirti Gupta, Navneet Singla, Ankur Kapoor
While giant cell tumor is commonly a tumor of long bones, involvement of sphenoid bone is very rare. Clinically and radiologically, it mimics other neoplasms of this site. Endochondral ossification of this bone during development explains its curious preferential involvement in comparison to the rest of the skull bones. We describe an example of such a tumor arising in the sphenoid bone in a young woman and discuss the differential diagnosis. Recognizing its characteristic features is important for correct interpretation...
September 19, 2016: Clinical Neuropathology
Michihiro Tanaka
BACKGROUND: The distribution of intracranial dural AVFs (DAVFs) may be affected by the embryological bony structures that consist of membranous bone and endochondral bone. METHODS: We retrospectively analyzed the distribution of the shunt points in 58 consecutive cases of DAVFs. Shunt points were identified with selective digital subtraction angiography, high-resolution cone beam computed tomography (CT), or three-dimensional rotation angiography. All the shunt points were plotted on the map of the skull base in relation to the topography of the endochondral bone and the membranous bone...
2016: Acta Neurochirurgica. Supplement
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)...
September 14, 2016: Stem Cells Translational Medicine
Thao M Nguyen, Agnieszka Arthur, Sharon Paton, Sarah Hemming, Romana Panagopoulos, John Codrington, Carl R Walkley, Andrew C W Zannettino, Stan Gronthos
The EphB receptor tyrosine kinase family and their ephrinB ligands have been implicated as mediators of skeletal development and bone homeostasis in humans, where mutations in ephrinB1 contribute to frontonasal dysplasia and coronal craniosynostosis. In mouse models, ephrinB1 has been shown to be a critical factor mediating osteoblast function. The present study examined the functional importance of ephrinB1 during endochondral ossification using the Cre recombination system with targeted deletion of ephrinB1 (EfnB1(fl/fl)) in osteogenic progenitor cells, under the control of the osterix (Osx:Cre) promoter...
September 10, 2016: Bone
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