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  1. Article ; Online: Niches for Skeletal Stem Cells of Mesenchymal Origin

    Anastasiia D. Kurenkova / Ekaterina V. Medvedeva / Phillip T. Newton / Andrei S. Chagin

    Frontiers in Cell and Developmental Biology, Vol

    2020  Volume 8

    Abstract: With very few exceptions, all adult tissues in mammals are maintained and can be renewed by stem cells that self-renew and generate the committed progeny required. These functions are regulated by a specific and in many ways unique microenvironment in ... ...

    Abstract With very few exceptions, all adult tissues in mammals are maintained and can be renewed by stem cells that self-renew and generate the committed progeny required. These functions are regulated by a specific and in many ways unique microenvironment in stem cell niches. In most cases disruption of an adult stem cell niche leads to depletion of stem cells, followed by impairment of the ability of the tissue in question to maintain its functions. The presence of stem cells, often referred to as mesenchymal stem cells (MSCs) or multipotent bone marrow stromal cells (BMSCs), in the adult skeleton has long been realized. In recent years there has been exceptional progress in identifying and characterizing BMSCs in terms of their capacity to generate specific types of skeletal cells in vivo. Such BMSCs are often referred to as skeletal stem cells (SSCs) or skeletal stem and progenitor cells (SSPCs), with the latter term being used throughout this review. SSPCs have been detected in the bone marrow, periosteum, and growth plate and characterized in vivo on the basis of various genetic markers (i.e., Nestin, Leptin receptor, Gremlin1, Cathepsin-K, etc.). However, the niches in which these cells reside have received less attention. Here, we summarize the current scientific literature on stem cell niches for the SSPCs identified so far and discuss potential factors and environmental cues of importance in these niches in vivo. In this context we focus on (i) articular cartilage, (ii) growth plate cartilage, (iii) periosteum, (iv) the adult endosteal compartment, and (v) the developing endosteal compartment, in that order.
    Keywords skeletal stem cells ; progenitors ; osteoblasts ; chondrocytes ; MSCs ; stem cell niche ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects

    Shabnam I. Ibragimova / Ekaterina V. Medvedeva / Irina A. Romanova / Leonid P. Istranov / Elena V. Istranova / Aleksey V. Lychagin / Andrey A. Nedorubov / Peter S. Timashev / Vladimir I. Telpukhov / Andrei S. Chagin

    International Journal of Molecular Sciences, Vol 23, Iss 292, p

    2022  Volume 292

    Abstract: Articular cartilage is a highly organized tissue that has a limited ability to heal. Tissue engineering is actively exploited for joint tissue reconstruction in numerous cases of articular cartilage degeneration associated with trauma, arthrosis, ... ...

    Abstract Articular cartilage is a highly organized tissue that has a limited ability to heal. Tissue engineering is actively exploited for joint tissue reconstruction in numerous cases of articular cartilage degeneration associated with trauma, arthrosis, rheumatoid arthritis, and osteoarthritis. However, the optimal scaffolds for cartilage repair are not yet identified. Here we have directly compared five various scaffolds, namely collagen-I membrane, collagen-II membrane, decellularized cartilage, a cellulose-based implant, and commercially available Chondro-Gide ® (Geistlich Pharma AG, Wolhusen, Switzerland) collagen membrane. The scaffolds were implanted in osteochondral full-thickness defects, formed on adult Wistar rats using a hand-held cutter with a diameter of 2.0 mm and a depth of up to the subchondral bone. The congruence of the articular surface was almost fully restored by decellularized cartilage and collagen type II-based scaffold. The most vivid restoration was observed 4 months after the implantation. The formation of hyaline cartilage was not detected in any of the groups. Despite cellular infiltration into scaffolds being observed in each group except cellulose, neither chondrocytes nor chondro-progenitors were detected. We concluded that for restoration of hyaline cartilage, scaffolds have to be combined either with cellular therapy or morphogens promoting chondrogenic differentiation.
    Keywords articular cartilage ; full-thickness defect ; scaffold ; collagen membrane ; decellularized cartilage ; cellulose ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 616
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Epiphyseal Cartilage Formation Involves Differential Dynamics of Various Cellular Populations During Embryogenesis

    Yi Zhang / Karl Annusver / Kazunori Sunadome / Polina Kameneva / Steven Edwards / Guanghua Lei / Maria Kasper / Andrei S. Chagin / Igor Adameyko / Meng Xie

    Frontiers in Cell and Developmental Biology, Vol

    2020  Volume 8

    Abstract: A joint connects two or more bones together to form a functional unit that allows different types of bending and movement. Little is known about how the opposing ends of the connected bones are developed. Here, applying various lineage tracing strategies ...

    Abstract A joint connects two or more bones together to form a functional unit that allows different types of bending and movement. Little is known about how the opposing ends of the connected bones are developed. Here, applying various lineage tracing strategies we demonstrate that progenies of Gdf5-, Col2-, Prrx1-, and Gli1-positive cells contribute to the growing epiphyseal cartilage in a spatially asymmetrical manner. In addition, we reveal that cells in the cartilaginous anlagen are likely to be the major sources for epiphyseal cartilage. Moreover, Gli1-positive cells are found to proliferate along the skeletal edges toward the periarticular region of epiphyseal surface. Finally, a switch in the mechanism of growth from cell division to cell influx likely occurs in the epiphyseal cartilage when joint cavitation has completed. Altogether, our findings reveal an asymmetrical mechanism of growth that drives the formation of epiphyseal cartilage ends, which might implicate on how the articular surface of these skeletal elements acquires their unique and sophisticated shape during embryonic development.
    Keywords joint ; cartilage ; clonal tracing ; asymmetrical ; dynamics ; embryonic development ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Repair of Damaged Articular Cartilage

    Ekaterina V. Medvedeva / Ekaterina A. Grebenik / Svetlana N. Gornostaeva / Vladimir I. Telpuhov / Aleksey V. Lychagin / Peter S. Timashev / Andrei S. Chagin

    International Journal of Molecular Sciences, Vol 19, Iss 8, p

    Current Approaches and Future Directions

    2018  Volume 2366

    Abstract: Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage ... ...

    Abstract Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.
    Keywords articular hyaline cartilage ; regenerative medicine approaches ; stem cells ; tissue-engineered constructs ; cell-based therapy ; micro-fracture ; mosaicplasty ; autologous chondrocyte implantation (ACI) ; matrix-induced autologous chondrocyte implantation (MACI) ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 616
    Language English
    Publishing date 2018-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Resveratrol treatment delays growth plate fusion and improves bone growth in female rabbits.

    Elham Karimian / Chen Tamm / Andrei S Chagin / Karin Samuelsson / Kristín Rós Kjartansdóttir / Claes Ohlsson / Lars Sävendahl

    PLoS ONE, Vol 8, Iss 6, p e

    2013  Volume 67859

    Abstract: Trans-resveratrol (RES), naturally produced by many plants, has a structure similar to synthetic estrogen diethylstilbestrol, but any effect on bone growth has not yet been clarified. Pre-pubertal ovary-intact New Zealand white rabbits received daily ... ...

    Abstract Trans-resveratrol (RES), naturally produced by many plants, has a structure similar to synthetic estrogen diethylstilbestrol, but any effect on bone growth has not yet been clarified. Pre-pubertal ovary-intact New Zealand white rabbits received daily oral administration of either vehicle (control) or RES (200 mg/kg) until growth plate fusion occurred. Bone growth and growth plate size were longitudinally monitored by X-ray imaging, while at the endpoint, bone length was assessed by a digital caliper. In addition, pubertal ovariectomized (OVX) rabbits were treated with vehicle, RES or estradiol cypionate (positive control) for 7 or 10 weeks and fetal rat metatarsal bones were cultured in vitro with RES (0.03 µM-50 µM) and followed for up to 19 days. In ovary-intact rabbits, sixteen-week treatment with RES increased tibiae and vertebrae bone growth and subsequently improved final length. In OVX rabbits, RES delayed fusion of the distal tibia, distal femur and proximal tibia epiphyses and femur length and vertebral bone growth increased when compared with controls. Histomorphometrical analysis showed that RES-treated OVX rabbits had a wider distal femur growth plate, enlarged resting zone, increased number/size of hypertrophic chondrocytes, increased height of the hypertrophic zone, and suppressed chondrocyte expression of VEGF and laminin. In cultured fetal rat metatarsal bones, RES stimulated growth at 0.3 µM while at higher concentrations (10 μM and 50 μM) growth was inhibited. We conclude that RES has the potential to improve longitudinal bone growth. The effect was associated with a delay of growth plate fusion resulting in increased final length. These effects were accompanied by a profound suppression of VEGF and laminin expression suggesting that impairment of growth plate vascularization might be an underlying mechanism.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Secondary ossification center induces and protects growth plate structure

    Meng Xie / Pavel Gol'din / Anna Nele Herdina / Jordi Estefa / Ekaterina V Medvedeva / Lei Li / Phillip T Newton / Svetlana Kotova / Boris Shavkuta / Aditya Saxena / Lauren T Shumate / Brian D Metscher / Karl Großschmidt / Shigeki Nishimori / Anastasia Akovantseva / Anna P Usanova / Anastasiia D Kurenkova / Anoop Kumar / Irene Linares Arregui /
    Paul Tafforeau / Kaj Fried / Mattias Carlström / András Simon / Christian Gasser / Henry M Kronenberg / Murat Bastepe / Kimberly L Cooper / Peter Timashev / Sophie Sanchez / Igor Adameyko / Anders Eriksson / Andrei S Chagin

    eLife, Vol

    2020  Volume 9

    Abstract: Growth plate and articular cartilage constitute a single anatomical entity early in development but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that ... ...

    Abstract Growth plate and articular cartilage constitute a single anatomical entity early in development but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of the ossification pattern in mammals with specialized extremities (whales, bats, jerboa) revealed that SOC development correlates with the extent of mechanical loads. Mathematical modeling revealed that SOC reduces mechanical stress within the growth plate. Functional experiments revealed the high vulnerability of hypertrophic chondrocytes to mechanical stress and showed that SOC protects these cells from apoptosis caused by extensive loading. Atomic force microscopy showed that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC has evolved to protect the hypertrophic chondrocytes from the high mechanical stress encountered in the terrestrial environment.
    Keywords growth plate ; chondrocytes ; whale ; bat ; jerboa ; secondary ossification ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 621
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Signals from the brain and olfactory epithelium control shaping of the mammalian nasal capsule cartilage

    Marketa Kaucka / Julian Petersen / Marketa Tesarova / Bara Szarowska / Maria Eleni Kastriti / Meng Xie / Anna Kicheva / Karl Annusver / Maria Kasper / Orsolya Symmons / Leslie Pan / Francois Spitz / Jozef Kaiser / Maria Hovorakova / Tomas Zikmund / Kazunori Sunadome / Michael P Matise / Hui Wang / Ulrika Marklund /
    Hind Abdo / Patrik Ernfors / Pascal Maire / Maud Wurmser / Andrei S Chagin / Kaj Fried / Igor Adameyko

    eLife, Vol

    2018  Volume 7

    Abstract: Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals ... ...

    Abstract Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts.
    Keywords mammalian face ; facial shaping ; embryonic development ; cartilage induction ; sonic hedgehog ; cleft palate ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2018-06-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate cartilage

    Marketa Kaucka / Tomas Zikmund / Marketa Tesarova / Daniel Gyllborg / Andreas Hellander / Josef Jaros / Jozef Kaiser / Julian Petersen / Bara Szarowska / Phillip T Newton / Vyacheslav Dyachuk / Lei Li / Hong Qian / Anne-Sofie Johansson / Yuji Mishina / Joshua D Currie / Elly M Tanaka / Alek Erickson / Andrew Dudley /
    Hjalmar Brismar / Paul Southam / Enrico Coen / Min Chen / Lee S Weinstein / Ales Hampl / Ernest Arenas / Andrei S Chagin / Kaj Fried / Igor Adameyko

    eLife, Vol

    2017  Volume 6

    Abstract: Cartilaginous structures are at the core of embryo growth and shaping before the bone forms. Here we report a novel principle of vertebrate cartilage growth that is based on introducing transversally-oriented clones into pre-existing cartilage. This ... ...

    Abstract Cartilaginous structures are at the core of embryo growth and shaping before the bone forms. Here we report a novel principle of vertebrate cartilage growth that is based on introducing transversally-oriented clones into pre-existing cartilage. This mechanism of growth uncouples the lateral expansion of curved cartilaginous sheets from the control of cartilage thickness, a process which might be the evolutionary mechanism underlying adaptations of facial shape. In rod-shaped cartilage structures (Meckel, ribs and skeletal elements in developing limbs), the transverse integration of clonal columns determines the well-defined diameter and resulting rod-like morphology. We were able to alter cartilage shape by experimentally manipulating clonal geometries. Using in silico modeling, we discovered that anisotropic proliferation might explain cartilage bending and groove formation at the macro-scale.
    Keywords chondrocranium ; scaling and shaping ; facial cartilage growth ; mouse mutants ; mathematical and material modelling ; Wnt/PCP ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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