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      Osteoblast migration in vertebrate bone : Osteoblast migration in vertebrate bone

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          Abstract

          Bone formation, for example during bone remodelling or fracture repair, requires mature osteoblasts to deposit bone with remarkable spatial precision. As osteoblast precursors derive either from circulation or resident stem cell pools, they and their progeny are required to migrate within the three-dimensional bone space and to navigate to their destination, i.e. to the site of bone formation. An understanding of this process is emerging based on in vitro and in vivo studies of several vertebrate species. Receptors on the osteoblast surface mediate cell adhesion and polarization, which induces osteoblast migration. Osteoblast migration is then facilitated along gradients of chemoattractants. The latter are secreted or released proteolytically by several cell types interacting with osteoblasts, including osteoclasts and vascular endothelial cells. The positions of these cellular sources of chemoattractants in relation to the position of the osteoblasts provide the migrating osteoblasts with tracks to their destination, and osteoblasts possess the means to follow a track marked by multiple chemoattractant gradients. In addition to chemotactic cues, osteoblasts sense other classes of signals and utilize them as landmarks for navigation. The composition of the osseous surface guides adhesion and hence migration efficiency and can also provide steering through haptotaxis. Further, it is likely that signals received from surface interactions modulate chemotaxis. Besides the nature of the surface, mechanical signals such as fluid flow may also serve as navigation signals for osteoblasts. Alterations in osteoblast migration and navigation might play a role in metabolic bone diseases such as osteoporosis.

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          Most cited references113

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          Cell migration: integrating signals from front to back.

          Cell migration is a highly integrated multistep process that orchestrates embryonic morphogenesis; contributes to tissue repair and regeneration; and drives disease progression in cancer, mental retardation, atherosclerosis, and arthritis. The migrating cell is highly polarized with complex regulatory pathways that spatially and temporally integrate its component processes. This review describes the mechanisms underlying the major steps of migration and the signaling pathways that regulate them, and outlines recent advances investigating the nature of polarity in migrating cells and the pathways that establish it.
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            Random versus directionally persistent cell migration.

            Directional migration is an important component of cell motility. Although the basic mechanisms of random cell movement are well characterized, no single model explains the complex regulation of directional migration. Multiple factors operate at each step of cell migration to stabilize lamellipodia and maintain directional migration. Factors such as the topography of the extracellular matrix, the cellular polarity machinery, receptor signalling, integrin trafficking, integrin co-receptors and actomyosin contraction converge on regulation of the Rho family of GTPases and the control of lamellipodial protrusions to promote directional migration.
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              Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels.

              During endochondral bone development, the first osteoblasts differentiate in the perichondrium surrounding avascular cartilaginous rudiments; the source of trabecular osteoblasts inside the later bone is, however, unknown. Here, we generated tamoxifen-inducible transgenic mice bred to Rosa26R-LacZ reporter mice to follow the fates of stage-selective subsets of osteoblast lineage cells. Pulse-chase studies showed that osterix-expressing osteoblast precursors, labeled in the perichondrium prior to vascular invasion of the cartilage, give rise to trabecular osteoblasts, osteocytes, and stromal cells inside the developing bone. Throughout the translocation, some precursors were found to intimately associate with invading blood vessels, in pericyte-like fashion. A similar coinvasion occurs during endochondral healing of bone fractures. In contrast, perichondrial mature osteoblasts did not exhibit perivascular localization and remained in the outer cortex of developing bones. These findings reveal the specific involvement of immature osteoblast precursors in the coupled vascular and osteogenic transformation essential to endochondral bone development and repair. 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Biological Reviews
                Biol Rev
                Wiley
                14647931
                February 2018
                February 2018
                June 19 2017
                : 93
                : 1
                : 350-363
                Affiliations
                [1 ]Bone Cell and Imaging Laboratory, Department of Orthopedics, Klinikum rechts der Isar; Ismaninger Straße 22, Technical University Munich; 81675 München Germany
                [2 ]Siegfried Weller Institute, BG Hospital; University of Tübingen, Schnarrenbergstraße 95; 72076 Tübingen Germany
                [3 ]Mineralized Tissue Laboratory; Research Division, Hospital for Special Surgery, 535 E 70th Street; New York NY 10021 U.S.A.
                Article
                10.1111/brv.12345
                6218945
                28631442
                3e52f910-3aeb-4c5e-bb4f-219f7a1d5b35
                © 2017

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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