Identification of a progenitor cell population destined to form fracture fibrocartilage callus in Dickkopf-related protein 3–green fluorescent protein reporter mice

Mori, Yu; Adams, Douglas; Hagiwara, Yusuke; Yoshida, Ruriko; Kamimura, Mikio; Itoi, Eiji

doi:10.1007/s00774-015-0711-1

Cited by 16 publications

(19 citation statements)

References 25 publications

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“…Firstly, there is a long-term quiescent tissue-resident progenitor population that contributes to a subset of osteoblasts and chondrocytes for at least 3 months after labeling. Secondly, there are cells that activate αSMA after injury, as visualized in studies using real-time αSMA reporters (30). The majority of osteoblasts are derived from αSMA-labeled cells when tamoxifen is given at the time of fracture.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated that αSMACreER identifies osteoprogenitors in both periosteum and the bone marrow compartment (21,22,29). Previously, we delivered tamoxifen at the time of fracture, which potentially labels cells that activate αSMA expression at the time of or shortly after fracture (30). In this study, we delivered tamoxifen up to 90 days before fracture to evaluate whether the reporter was identifying long-term progenitor cells.…”

Section: In Vivo Identification Of Long-term Osteochondroprogenitorsmentioning

confidence: 99%

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Heterogeneity of murine periosteum progenitors involved in fracture healing

Matthews

Novak

Sbrana

et al. 2020

Preprint

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The periosteum is the major source of cells involved in fracture healing. We sought to characterize differences in progenitor cell populations between periosteum and other bone compartments, and identify periosteal cells involved in fracture healing. The periosteum is highly enriched for progenitor cells, including Sca1+ cells, CFU-F and label-retaining cells. Lineage tracing with αSMACreER identifies periosteal cells that contribute to >80% of osteoblasts and ~40% of chondrocytes following fracture.A subset of αSMA+ cells are quiescent long-term injury-responsive progenitors. Ablation of αSMA+ cells impairs fracture callus formation. In addition, committed osteoblast-lineage cells contributed around 10% of osteoblasts, but no chondrocytes in fracture calluses. Most periosteal progenitors, particularly those that form osteoblasts, can be targeted by αSMACreER. We have demonstrated that the periosteum is highly enriched for skeletal stem and progenitor cells and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing.

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Section: Discussionmentioning

confidence: 99%

Section: In Vivo Identification Of Long-term Osteochondroprogenitorsmentioning

confidence: 99%

Heterogeneity of murine periosteum progenitors involved in fracture healing

Matthews

Novak

Sbrana

et al. 2020

Preprint

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“…The surgical procedure was performed under inhalation anesthesia with 2% isoflurane (Forene; Abbott, Wiesbaden, Germany). Closed transverse diaphyseal fractures were created, followed by intramedullary insertion of Ti‐Nb‐Sn alloy wires into the right tibiae using a fracture device, as previously described . All intramedullary nails were 0.4 mm in diameter and 17 mm in length.…”

Section: Methodsmentioning

confidence: 99%

“…Closed transverse diaphyseal fractures were created, followed by intramedullary insertion of Ti-Nb-Sn alloy wires into the right tibiae using a fracture device, as previously described. 24,25 All intramedullary nails were 0.4 mm in diameter and 17 mm in length. The fracture device functioned via a blunt guillotine driven by a 230-g weight dropping from a height of 17 cm.…”

Section: Microstructural Observation and Crystallographic Analysismentioning

confidence: 99%

Effects of intramedullary nails composed of a new β‐type Ti‐Nb‐Sn alloy with low Young's modulus on fracture healing in mouse tibiae

et al. 2018

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The influence of Young's moduli of materials on the fracture healing process remains unclear. This study aimed to assess the effects of intramedullary nails composed of materials with low Young's moduli on fracture repair. We previously developed a β-type Ti-Nb-Sn alloy with low Young's modulus close to that of human cortical bone. Here, we prepared two Ti-Nb-Sn alloys with Young's moduli of 45 and 78 GPa by heat treatment, and compared their effects on fracture healing. Fracture and nailing were performed in the right tibiae of C57BL/6 mice. The bone healing process was evaluated by microcomputed tomography (micro-CT), histomorphometry, and RT-PCR. We found larger bone volumes of fracture callus in the mice treated with the 45-GPa Ti-Nb-Sn alloy as compared with the 78-GPa Ti-Nb-Sn alloy in micro-CT analyses. This was confirmed with histology at day 14, with accelerated new bone formation and cartilage absorption in the 45-GPa Ti-Nb-Sn group compared with the 78-GPa Ti-Nb-Sn group. Acp5 expression was lower in the 45-GPa Ti-Nb-Sn group than in the 78-GPa Ti-Nb-Sn group at day 10. These findings indicate that intramedullary fixation with nails with a lower Young's modulus offer a greater capacity for fracture repair. Our 45-GPa Ti-Nb-Sn alloy is a promising material for fracture treatment implants. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2841-2848, 2018.

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“…Various reporters have also been useful for closely monitoring the fracture healing process. [46, 68, 69]. ES cell lines have also been generated from mice harboring promoter-FP transgenes in order to monitor differentiation of ES-derived progenitor cells in vitro and in vivo [70, 71].…”

Section: Isolation Of Osteoblast Lineage Cells Based On the Expressiomentioning

confidence: 99%

Visual reporters for study of the osteoblast lineage

Roeder

Matthews

Kalajzić

2016

Bone

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Advancing our understanding of osteoblast biology and differentiation is critical to elucidate the pathological mechanisms responsible for skeletal diseases such as osteoporosis. Histology and histomorphometry, the classical methods to study osteoblast biology, identify osteoblasts based on their location and morphology and ability to mineralize matrix, but do not clearly define their stage of differentiation. Introduction of visual transgenes into the cells of osteoblast lineage has revolutionized the field and resulted in a paradigm shift that allowed for specific identification and isolation of subpopulations within the osteoblast lineage. Knowledge acquired from the studies based on GFP transgenes has allowed for more precise interpretation of studies analyzing targeted overexpression or deletion of genes in the osteoblast lineage. Here, we provide a condensed overview of the currently available promoter-fluorescent reporter transgenic mice that have been generated and evaluated to varying extents. We cover different stages of the lineage as transgenes have been utilized to identify osteoprogenitiors, pre-osteoblasts, osteoblasts, or osteocytes. We show that each of these promoters present with advantages and disadvantages. The studies based on the use of these reporter mice have improved our understanding of bone biology. They constitute attractive models to target osteoblasts and help to understand their cell biology.

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Identification of a progenitor cell population destined to form fracture fibrocartilage callus in Dickkopf-related protein 3–green fluorescent protein reporter mice

Cited by 16 publications

References 25 publications

Heterogeneity of murine periosteum progenitors involved in fracture healing

Heterogeneity of murine periosteum progenitors involved in fracture healing

Effects of intramedullary nails composed of a new β‐type Ti‐Nb‐Sn alloy with low Young's modulus on fracture healing in mouse tibiae

Visual reporters for study of the osteoblast lineage

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