19 results on '"Fiedler, Imke A. K."'
Search Results
2. Bone quality analysis of jaw bones in individuals with type 2 diabetes mellitus—post mortem anatomical and microstructural evaluation
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Rodic, Teodora, Wölfel, Eva Maria, Milovanovic, Petar, Fiedler, Imke A. K., Cvetkovic, Danica, Jähn, Katharina, Amling, Michael, Sopta, Jelena, Nikolic, Slobodan, Zivkovic, Vladimir, Busse, Björn, and Djuric, Marija
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- 2021
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3. When Cortical Bone Matrix Properties Are Indiscernible between Elderly Men with and without Type 2 Diabetes, Fracture Resistance Follows Suit
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Wölfel, Eva M., primary, Bartsch, Benjamin, additional, Koldehoff, Jasmin, additional, Fiedler, Imke A. K., additional, Dragoun‐Kolibova, Sofie, additional, Schmidt, Felix N., additional, Krug, Johannes, additional, Lin, Mei‐Chun, additional, Püschel, Klaus, additional, Ondruschka, Benjamin, additional, Zimmermann, Elizabeth A., additional, Jelitto, Hans, additional, Schneider, Gerold, additional, Gludovatz, Bernd, additional, and Busse, Björn, additional
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- 2023
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4. Zebrafish Tric-b is required for skeletal development and bone cells differentiation
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Tonelli, Francesca, primary, Leoni, Laura, additional, Daponte, Valentina, additional, Gioia, Roberta, additional, Cotti, Silvia, additional, Fiedler, Imke A. K., additional, Larianova, Daria, additional, Willaert, Andy, additional, Coucke, Paul J., additional, Villani, Simona, additional, Busse, Björn, additional, Besio, Roberta, additional, Rossi, Antonio, additional, Witten, P. Eckhard, additional, and Forlino, Antonella, additional
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- 2023
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5. wnt16 regulates spine and muscle morphogenesis through parallel signals from notochord and dermomyotome
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Watson, Claire J., primary, Tang, W. Joyce, additional, Rojas, Maria F., additional, Fiedler, Imke A. K., additional, Morfin Montes de Oca, Ernesto, additional, Cronrath, Andrea R., additional, Callies, Lulu K., additional, Swearer, Avery Angell, additional, Ahmed, Ali R., additional, Sethuraman, Visali, additional, Addish, Sumaya, additional, Farr, Gist H., additional, Gómez, Arianna Ericka, additional, Rai, Jyoti, additional, Monstad-Rios, Adrian T., additional, Gardiner, Edith M., additional, Karasik, David, additional, Maves, Lisa, additional, Busse, Bjorn, additional, Hsu, Yi-Hsiang, additional, and Kwon, Ronald Young, additional
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- 2022
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6. Bone phenotyping approaches in human, mice and zebrafish - expert overview of the EU cost action GEMSTONE ('GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork')
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Foessl, Ines, Bassett, J. H. Duncan, Bjørnerem, Åshild, Busse, Björn, Calado, Ângelo, Chavassieux, Pascale, Christou, Maria, Douni, Eleni, Fiedler, Imke A. K., Fonseca, João Eurico, Hassler, Eva, Högler, Wolfgang, Kague, Erika, Karasik, David, Khashayar, Patricia, Langdahl, Bente L., Leitch, Victoria D., Lopes, Philippe, Markozannes, Georgios, McGuigan, Fiona E. A., Medina-Gomez, Carolina, Ntzani, Evangelia, Oei, Ling, Ohlsson, Claes, Szulc, Pawel, Tobias, Jonathan H., Trajanoska, Katerina, Tuzun, Şansın, Valjevac, Amina, van Rietbergen, Bert, Williams, Graham R., Zekic, Tatjana, Rivadeneira, Fernando, Obermayer-Pietsch, Barbara, Wellcome Trust, and Repositório da Universidade de Lisboa
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Proteomics ,IN-VIVO ASSESSMENT ,Technology and Engineering ,phenotyping ,Musculoskeletal Physiological Phenomena ,VERTEBRAL FRACTURE ASSESSMENT ,Review ,TURNOVER MARKERS ,Bone and Bones ,bone and skeletal diseases ,Mice ,Endocrinology & Metabolism ,Endocrinology ,Animals ,Humans ,Gene Regulatory Networks ,BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine ,Zebrafish ,BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina ,Science & Technology ,COST ,QUANTITATIVE COMPUTED-TOMOGRAPHY ,MINERALIZATION DENSITY DISTRIBUTION ,Biology and Life Sciences ,imaging ,HIP FRACTURE ,1103 Clinical Sciences ,Genomics ,BRANCHIAL ARCH MUTANTS ,X-RAY ABSORPTIOMETRY ,MECHANICAL-PROPERTIES ,REFERENCE POINT INDENTATION ,osteoporosis ,animal models ,GEMSTONE ,Diabetes and Metabolism ,Phenotype ,Models, Animal ,Phenotype, osteoporosis ,1111 Nutrition and Dietetics ,GEMSTONECOST ,Life Sciences & Biomedicine - Abstract
Copyright © 2021 Foessl, Bassett, Bjørnerem, Busse, Calado, Chavassieux, Christou, Douni, Fiedler, Fonseca, Hassler, Högler, Kague, Karasik, Khashayar, Langdahl, Leitch, Lopes, Markozannes, McGuigan, Medina-Gomez, Ntzani, Oei, Ohlsson, Szulc, Tobias, Trajanoska, Tuzun, Valjevac, van Rietbergen, Williams, Zekic, Rivadeneira and Obermayer-Pietsch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms., A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art technologies to investigate bone properties in humans and animals - including their strengths and weaknesses. New research methodologies are outlined and future strategies are discussed to combine phenotypic with rapidly developing -omics data in order to advance musculoskeletal research and move towards "personalised medicine"., Funding was obtained from the GEMSTONE COST Action (CA18139). The Origins of Bone and Cartilage Disease Programme analysed the skeletal phenotypes of knockout mice generated by the International Mouse Phenotyping Consortium (IMPC) and was funded by a Welcome Trust Strategic Award (101123) to GRW and JHDB. IF is enrolled in the PhD program MOLIN at the Medical University of Graz, funded by the Austrian Science Fund (FWF). FM is funded by the Swedish Research Council (2018-02981), Greta and Johan Kock Foundation, the A. Påhlsson, A. Osterlund Foundation and H Järnhardt Foundations, King Gustav V 80 year fund, Swedish Rheumatism foundation, Skåne University Hospital Research Fund, Research and Development Council of Region Skåne.
- Published
- 2021
7. Collagen Fiber Orientation Is Coupled with Specific Nano-Compositional Patterns in Dark and Bright Osteons Modulating Their Biomechanical Properties
- Author
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Stockhausen, Kilian E., primary, Qwamizadeh, Mahan, additional, Wölfel, Eva M., additional, Hemmatian, Haniyeh, additional, Fiedler, Imke A. K., additional, Flenner, Silja, additional, Longo, Elena, additional, Amling, Michael, additional, Greving, Imke, additional, Ritchie, Robert O., additional, Schmidt, Felix N., additional, and Busse, Björn, additional
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- 2021
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8. More Bone with Less Minerals? The Effects of Dietary Phosphorus on the Post-Cranial Skeleton in Zebrafish
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Cotti, Silvia, primary, Huysseune, Ann, additional, Koppe, Wolfgang, additional, Rücklin, Martin, additional, Marone, Federica, additional, Wölfel, Eva M., additional, Fiedler, Imke A. K., additional, Busse, Björn, additional, Forlino, Antonella, additional, and Witten, P. Eckhard, additional
- Published
- 2020
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9. Biomimetics: On the Origins of Fracture Toughness in Advanced Teleosts: How the Swordfish Sword's Bone Structure and Composition Allow for Slashing under Water to Kill or Stun Prey (Adv. Sci. 12/2019)
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Schmidt, Felix N., primary, Zimmermann, Elizabeth A., additional, Walsh, Flynn, additional, Plumeyer, Christine, additional, Schaible, Eric, additional, Fiedler, Imke A. K., additional, Milovanovic, Petar, additional, Rößle, Manfred, additional, Amling, Michael, additional, Blanchet, Clément, additional, Gludovatz, Bernd, additional, Ritchie, Robert O., additional, and Busse, Björn, additional
- Published
- 2019
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10. On the Origins of Fracture Toughness in Advanced Teleosts: How the Swordfish Sword's Bone Structure and Composition Allow for Slashing under Water to Kill or Stun Prey
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Schmidt, Felix N., primary, Zimmermann, Elizabeth A., additional, Walsh, Flynn, additional, Plumeyer, Christine, additional, Schaible, Eric, additional, Fiedler, Imke A. K., additional, Milovanovic, Petar, additional, Rößle, Manfred, additional, Amling, Michael, additional, Blanchet, Clément, additional, Gludovatz, Bernd, additional, Ritchie, Robert O., additional, and Busse, Björn, additional
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- 2019
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11. Increased mechanical loading through controlled swimming exercise induces bone formation and mineralization in adult zebrafish
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Suniaga, Santiago, primary, Rolvien, Tim, additional, vom Scheidt, Annika, additional, Fiedler, Imke A. K., additional, Bale, Hrishikesh A., additional, Huysseune, Ann, additional, Witten, P. Eckhard, additional, Amling, Michael, additional, and Busse, Björn, additional
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- 2018
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12. Collagen Fiber Orientation Is Coupled with Specific Nano-Compositional Patterns in Darkand BrightOsteons Modulating Their Biomechanical Properties
- Author
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Stockhausen, Kilian E., Qwamizadeh, Mahan, Wölfel, Eva M., Hemmatian, Haniyeh, Fiedler, Imke A. K., Flenner, Silja, Longo, Elena, Amling, Michael, Greving, Imke, Ritchie, Robert O., Schmidt, Felix N., and Busse, Björn
- Abstract
Bone continuously adapts to its mechanical environment by structural reorganization to maintain mechanical strength. As the adaptive capabilities of bone are portrayed in its nano- and microstructure, the existence of darkand brightosteons with contrasting preferential collagen fiber orientation (longitudinal and oblique-angled, respectively) points at a required tissue heterogeneity that contributes to the excellent fracture resistance mechanisms in bone. Darkand brightosteons provide an exceptional opportunity to deepen our understanding of how nanoscale tissue properties influence and guide fracture mechanisms at larger length scales. To this end, a comprehensive structural, compositional, and mechanical assessment is performed using circularly polarized light microscopy, synchrotron nanocomputed tomography, focused ion beam/scanning electron microscopy, quantitative backscattered electron imaging, Fourier transform infrared spectroscopy, and nanoindentation testing. To predict how the mechanical behavior of osteons is affected by shifts in collagen fiber orientation, finite element models are generated. Fundamental disparities between both osteon types are observed: darkosteons are characterized by a higher degree of mineralization along with a higher ratio of inorganic to organic matrix components that lead to higher stiffness and the ability to resist plastic deformation under compression. On the contrary, brightosteons contain a higher fraction of collagen and provide enhanced ductility and energy dissipation due to lower stiffness and hardness.
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- 2021
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13. Effect of short-term formaldehyde fixation on Raman spectral parameters of bone quality.
- Author
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Fiedler, Imke A. K., Casanova, Michele, Keplinger, Tobias, Busse, Björn, and Müller, Ralph
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ANALYSIS of bones , *RAMAN spectra , *BIOMECHANICS , *HISTOLOGY , *FORMALDEHYDE - Abstract
Medical knowledge of the skeleton including its structures has improved constantly over the past decades. Advanced imaging methods, mechanical testing and optical techniques have revealed insights into bone architecture and composition. Most of these advancements were possible due to the ex vivo investigation of biological tissues. Investigations of fresh tissue are generally preferred over preserved or fixed samples. However, chemical fixation is sometimes inevitable due to histological procedures or logistical reasons. The aim of this study was to investigate whether short-term chemical fixation with formaldehyde affects bone quality parameters obtained from Raman spectroscopy and if these effects last for intermediate sample storage of several hours. As formaldehyde induces cross-links to the organic components in bone tissue, we hypothesized that collagen-related parameters are particularly affected. Femurs of eight 17-week-old C57BL/6 mice were extracted and divided into two groups (N = 8 / group). Samples of the first group were fixed by immersion in 4% formaldehyde (PFA-solution) for 12 h at 4°C (fixed group) while samples of the second group were left untreated (unfixed group). Raman spectroscopy was performed, and repeated after 4 h, to assess whether intermediate storage time influenced the obtained results. Based on resultant spectra, mineral-to-matrix ratio, carbonate-to-phosphate ratio, carbonate-to-amide I ratio, mineral crystallinity and collagen maturity were determined. Carbonate-to-phosphate ratio was the only parameter showing a significant difference between the first and the subsequent measurements. For both groups, ratios showed a decrease in carbonate substitution compared to the first measurement (percentage decrease: 3.1% in fixed, 4.7% in unfixed). Collagen maturity of samples, which were short-term fixed with formaldehyde, was significantly lower than of fresh, unfixed samples (percentage difference: 3.8%). Our study shows that Raman spectroscopy is able to detect changes in collagen structure initiated by formaldehyde and that changes in short-term fixed samples are minimally influencing bone material properties measured with Raman spectroscopy. [ABSTRACT FROM AUTHOR]
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- 2018
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14. Severely Impaired Bone Material Quality in Chihuahua Zebrafish Resembles Classical Dominant Human Osteogenesis Imperfecta.
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Fiedler, Imke A. K., Schmidt, Felix N., Wölfel, Eva M., Plumeyer, Christine, Milovanovic, Petar, Gioia, Roberta, Tonelli, Francesca, Bale, Hrishikesh A., Jähn, Katharina, Besio, Roberta, Forlino, Antonella, and Busse, Björn
- Abstract
ABSTRACT: Excessive skeletal deformations and brittle fractures in the vast majority of patients suffering from osteogenesis imperfecta (OI) are a result of substantially reduced bone quality. Because the mechanical competence of bone is dependent on the tissue characteristics at small length scales, it is of crucial importance to assess how OI manifests at the micro‐ and nanoscale of bone. In this context, the Chihuahua (Chi/+) zebrafish, carrying a heterozygous glycine substitution in the α1 chain of collagen type I, has recently been proposed as a suitable animal model of classical dominant OI, showing skeletal deformities, altered mineralization patterns, and a smaller body size. This study assessed the bone quality properties of Chi/+ at multiple length scales using micro‐computed tomography (micro‐CT), histomorphometry, quantitative back‐scattered electron imaging, Fourier‐transform infrared spectroscopy, nanoindentation, and X‐ray microscopy. At the skeletal level, the Chi/+ displays smaller body size, deformities, and fracture calli in the ribs. Morphological changes at the whole bone level showed that the vertebrae in Chi/+ had a smaller size, smaller thickness, and distorted shape. At the tissue level, Chi/+ displayed a higher degree of mineralization, lower collagen maturity, lower mineral maturity, altered osteoblast morphology, and lower osteocyte lacunar density compared to wild‐type zebrafish. The alterations in the cellular, compositional, and structural properties of Chi/+ bones bear an explanation for the impaired local mechanical properties, which promote an increase in overall bone fragility in Chi/+. The quantitative assessment of bone quality in Chi/+ thus further validates this mutant as an important model reflecting osseous characteristics associated with human classical dominant OI. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]
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- 2018
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15. Human tibial cortical bone with high porosity in type 2 diabetes mellitus is accompanied by distinctive bone material properties.
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Wölfel EM, Fiedler IAK, Dragoun Kolibova S, Krug J, Lin MC, Yazigi B, Siebels AK, Mushumba H, Wulff B, Ondruschka B, Püschel K, Glüer CC, Jähn-Rickert K, and Busse B
- Subjects
- Humans, Tibia, X-Ray Microtomography methods, Porosity, Bone Density, Cortical Bone, Bone and Bones metabolism, Absorptiometry, Photon, Amides, Diabetes Mellitus, Type 2, Fractures, Bone
- Abstract
Diabetes mellitus is a metabolic disease affecting bone tissue at different length-scales. Higher fracture risk in diabetic patients is difficult to detect with common clinical fracture risk assessment due to normal or high bone mineral density in diabetic patients. The observed higher fracture risk despite normal to high areal bone mineral density in diabetic patients points towards impaired bone material quality. Here, we analyze tibial bone from individuals with type 2 diabetes mellitus using a multiscale-approach, which includes clinical and laboratory-based bone quality measures. Tibial cortical bone tissue from individuals with type 2 diabetes mellitus (T2DM) and age-matched healthy controls (n = 15 each) was analyzed with in situ impact indentation, dual energy X-ray absorptiometry (DXA), high resolution peripheral microcomputed tomography (HR-pQCT), micro-computed tomography (microCT), cyclic indentation, quantitative backscattered electron microscopy (qBEI), vibrational spectroscopy (Raman), nanoindentation, and fluorescence spectroscopy. With this approach, a high cortical porosity subgroup of individuals with T2DM was discriminated from two study groups: individuals with T2DM and individuals without T2DM, while both groups were associated with similar cortical porosity quantified by means of microCT. The high porosity T2DM group, but not the T2DM group, showed compromised bone quality expressed by altered cyclic indentation properties (transversal direction) in combination with a higher carbonate-to-amide I ratio in endocortical bone. In addition, in the T2DM group with high cortical porosity group, greater cortical pore diameter was identified with HR-pQCT and lower tissue mineral density using microCT, both compared to T2DM group. Micromechanical analyses of cross-sectioned osteons (longitudinal direction) with cyclic indentation, qBEI, and nanoindentation showed no differences between the three groups. High tibial cortical porosity in T2DM can be linked to locally altered bone material composition. As the tibia is an accessible skeletal site for fracture risk assessment in the clinics (CT, indentation), our findings may contribute to further understanding the site-specific structural and compositional factors forming the basis of bone quality in diabetes mellitus. Refined diagnostic strategies are needed for a comprehensive fracture risk assessment in diabetic bone disease., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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16. Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").
- Author
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Foessl I, Bassett JHD, Bjørnerem Å, Busse B, Calado Â, Chavassieux P, Christou M, Douni E, Fiedler IAK, Fonseca JE, Hassler E, Högler W, Kague E, Karasik D, Khashayar P, Langdahl BL, Leitch VD, Lopes P, Markozannes G, McGuigan FEA, Medina-Gomez C, Ntzani E, Oei L, Ohlsson C, Szulc P, Tobias JH, Trajanoska K, Tuzun Ş, Valjevac A, van Rietbergen B, Williams GR, Zekic T, Rivadeneira F, and Obermayer-Pietsch B
- Subjects
- Animals, Bone and Bones pathology, Gene Regulatory Networks physiology, Humans, Mice, Models, Animal, Phenotype, Proteomics methods, Zebrafish, Bone and Bones metabolism, Genomics methods, Musculoskeletal Physiological Phenomena genetics
- Abstract
A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art technologies to investigate bone properties in humans and animals - including their strengths and weaknesses. New research methodologies are outlined and future strategies are discussed to combine phenotypic with rapidly developing -omics data in order to advance musculoskeletal research and move towards "personalised medicine"., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Foessl, Bassett, Bjørnerem, Busse, Calado, Chavassieux, Christou, Douni, Fiedler, Fonseca, Hassler, Högler, Kague, Karasik, Khashayar, Langdahl, Leitch, Lopes, Markozannes, McGuigan, Medina-Gomez, Ntzani, Oei, Ohlsson, Szulc, Tobias, Trajanoska, Tuzun, Valjevac, van Rietbergen, Williams, Zekic, Rivadeneira and Obermayer-Pietsch.)
- Published
- 2021
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17. Breaking new ground in mineralized tissue: Assessing tissue quality in clinical and laboratory studies.
- Author
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Zimmermann EA, Fiedler IAK, and Busse B
- Subjects
- Bone and Bones diagnostic imaging, Humans, Spectroscopy, Fourier Transform Infrared, Tomography, X-Ray Computed, Fractures, Bone diagnostic imaging, Laboratories
- Abstract
Mineralized tissues, such as bone and teeth, have extraordinary mechanical properties of both strength and toughness. This mechanical behavior originates from deformation and fracture resistance mechanisms in their multi-scale structure. The term quality describes the matrix composition, multi-scale structure, remodeling dynamics, water content, and micro-damage accumulation in the tissue. Aging and disease result in changes in the tissue quality that may reduce strength and toughness and lead to elevated fracture risk. Therefore, the capability to measure the quality of mineralized tissues provides critical information on disease progression and mechanical integrity. Here, we provide an overview of clinical and laboratory-based techniques to assess the quality of mineralized tissues in health and disease. Current techniques used in clinical settings include radiography-based (radiographs, dual energy x-ray absorptiometry, EOS) and x-ray tomography-based methods (high resolution peripheral quantitative computed tomography, cone beam computed tomography). In the laboratory, tissue quality can be investigated in ex vivo samples with x-ray imaging (micro and nano-computed tomography, x-ray microscopy), electron microscopy (scanning/transmission electron imaging (SEM/STEM), backscattered scanning electron microscopy, Focused Ion Beam-SEM), light microscopy, spectroscopy (Raman spectroscopy and Fourier transform infrared spectroscopy) and assessment of mechanical behavior (mechanical testing, fracture mechanics and reference point indentation). It is important for clinicians and basic science researchers to be aware of the techniques available in different types of research. While x-ray imaging techniques translated to the clinic have provided exceptional advancements in patient care, the future challenge will be to incorporate high-resolution laboratory-based bone quality measurements into clinical settings to broaden the depth of information available to clinicians during diagnostics, treatment and management of mineralized tissue pathologies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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18. Disruption of the hepcidin/ferroportin regulatory circuitry causes low axial bone mass in mice.
- Author
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Ledesma-Colunga MG, Baschant U, Fiedler IAK, Busse B, Hofbauer LC, Muckenthaler MU, Altamura S, and Rauner M
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- Animals, Hepcidins genetics, Hepcidins metabolism, Male, Mice, Mice, Knockout, Cation Transport Proteins genetics, Hemochromatosis, Iron Overload
- Abstract
Ferroportin (FPN) is the only known iron exporter. Mutations conferring resistance of FPN to hepcidin-mediated degradation cause the iron overload disorder hereditary hemochromatosis type 4. While iron overload is associated with low bone mass, the mechanisms involved are not completely understood. Here, we aimed to investigate whether the disruption in the hepcidin/FPN axis in Fpn
C326S mice and subsequent systemic iron accumulation impacts on bone tissue to a similar extent as in Hfe-/- mice, which are hallmarked by a milder iron overload phenotype. Hfe-/- and FpnC326S mice show increased plasma iron levels and liver iron content, whereas iron overload was more pronounced in FpnC326S compared to Hfe-/- mice. Bone volume fraction and trabecular thickness at the femur were not different between 10 and 14-week-old male wild-type (WT), Hfe-/- and FpnC326S mice. By contrast, both Hfe-/- and FpnC326S mice exhibited a lower bone volume fraction [Hfe-/- , 24%; FpnC326S , 33%; p < 0.05] and trabecular thickness [Hfe-/- , 10%; FpnC326S , 15%; p < 0.05] in the fourth lumbar vertebra compared to WT mice. Analysis of the bone formation rate at the tibia showed no difference in both genotypes, but it was reduced in the vertebral bone of FpnC326S [36%, p < 0.05] compared to WT mice. Serum levels of the bone formation marker, P1NP, were significantly reduced in both, Hfe-/- and FpnC326S compared with WT mice [Hfe-/- , 35%; FpnC326S , 40%; p < 0.05]. Also, the intrinsic differentiation capacity of FpnC326S osteoblasts was impaired. Osteoclast parameters were not grossly affected. Interestingly, the liver iron content and plasma iron levels negatively correlated with the bone formation rate and serum levels of P1NP. Thus, disruption of the hepcidin/ferroportin regulatory axis in FpnC326S mice results in axial bone loss due to suppressed bone formation., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
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19. The different distribution of enzymatic collagen cross-links found in adult and children bone result in different mechanical behavior of collagen.
- Author
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Depalle B, Duarte AG, Fiedler IAK, Pujo-Menjouet L, Buehler MJ, and Berteau JP
- Subjects
- Adolescent, Aged, Bone Matrix metabolism, Bone and Bones pathology, Child, Computer Simulation, Elastic Modulus, Extracellular Matrix metabolism, Humans, Middle Aged, Stress, Mechanical, Bone Diseases metabolism, Bone and Bones metabolism, Collagen chemistry, Elasticity
- Abstract
Enzymatic collagen cross-linking has been shown to play an important role in the macroscopic elastic and plastic deformation of bone across ages. However, its direct contribution to collagen fibril deformation is unknown. The aim of this study is to determine how covalent intermolecular connections from enzymatic collagen cross-links contribute to collagen fibril elastic and plastic deformation of adults and children's bone matrix. We used ex vivo data previously obtained from biochemical analysis of children and adults bone samples (n = 14; n = 8, respectively) to create 22 sample-specific computational models of cross-linked collagen fibrils. By simulating a tensile test for each fibril, we computed the modulus of elasticity (E), ultimate tensile and yield stress (σ
u and σy ), and elastic, plastic and total work (We , Wp and Wtot ) for each collagen fibril. We present a novel difference between children and adult bone in the deformation of the collagen phase and suggest a link between collagen fibril scale and macroscale for elastic behavior in children bone under the influence of immature enzymatic cross-links. We show a parametric linear correlation between We and immature enzymatic collagen cross-links at the collagen fibril scale in the children population that is similar to the one we found at the macroscale in our previous study. Finally, we suggest the key role of covalent intermolecular connections to stiffness parameters (e.g. elastic modulus and We ) in children's collagen fibril and to toughness parameters in adult's collagen fibril, respectively., (Copyright © 2018. Published by Elsevier Inc.)- Published
- 2018
- Full Text
- View/download PDF
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