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      Role of osteopontin in bone remodeling and orthodontic tooth movement: a review

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          Abstract

          In this review, most of the known and postulated mechanisms of osteopontin (OPN) and its role in bone remodeling and orthodontic tooth movement are discussed based on available literature. OPN, a multifunctional protein, is considered crucial for bone remodeling, biomineralization, and periodontal remodeling during mechanical tension and stress (orthodontic tooth movement). It contributes to bone remodeling by promoting osteoclastogenesis and osteoclast activity through CD44- and αvβ3 -mediated cell signaling. Further, it has a definitive role in bone remodeling by the formation of podosomes, osteoclast survival, and osteoclast motility. OPN has been shown to have a regulatory effect on hydroxyapatite crystal (HAP) growth and potently inhibits the mineralization of osteoblast cultures in a phosphate-dependent manner. Bone remodeling is vital for orthodontic tooth movement. Significant compressive and tensional forces on the periodontium induce the signaling pathways mediated by various osteogenic genes including OPN, bone sialoprotein, Osterix, and osteocalcin. The signaling pathways involved in the regulation of OPN and its effect on the periodontal tissues during orthodontic tooth movement are further discussed in this review. A limited number of studies have suggested the use of OPN as a biomarker to assess orthodontic treatment. Furthermore, the association of single nucleotide polymorphisms (SNPs) in OPN coding gene Spp1 with orthodontically induced root resorption remains largely unexplored. Accordingly, future research directions for OPN are outlined in this review.

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          Most cited references66

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          Adhesion signaling - crosstalk between integrins, Src and Rho.

          Interactions between cells and the extracellular matrix coordinate signaling pathways that control various aspects of cellular behavior. Integrins sense the physical properties of the extracellular matrix and organize the cytoskeleton accordingly. In turn, this modulates signaling pathways that are triggered by various other transmembrane receptors and augments the cellular response to growth factors. Over the past years, it has become clear that there is extensive crosstalk between integrins, Src-family kinases and Rho-family GTPases at the heart of such adhesion signaling. In this Commentary, we discuss recent advances in our understanding of the dynamic regulation of the molecular connections between these three protein families. We also discuss how this signaling network can regulate a range of cellular processes that are important for normal tissue function and disease, including cell adhesion, spreading, migration and mechanotransduction.
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            Osteopontin: role in cell signaling and cancer progression.

            Cell migration and degradation of the extracellular matrix (ECM) are crucial steps in tumor progression. Several matrix-degrading proteases, including matrix metalloproteases, are highly regulated by growth factors, cytokines and ECM proteins. Osteopontin (OPN), a chemokine-like, calcified ECM-associated protein, plays a crucial role in determining the metastatic potential of various cancers. Since its first identification in bone, the multifaceted roles of OPN have been an area of intense investigation. Extensive research has elucidated the pivotal role of OPN in regulating the cell signaling that controls tumor progression and metastasis. This review focuses on recent advances in understanding the functional role of the OPN-induced signaling pathway in the regulation of cell migration and tumor progression and the implications for identifying novel targets for cancer therapy.
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              Ca2+-NFATc1 signaling is an essential axis of osteoclast differentiation.

              Osteoclasts are unique, multinucleated giant cells that decalcify and degrade the bone matrix. They originate from hematopoietic cells and their differentiation is dependent on a tumor necrosis factor (TNF) family cytokine, receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL), as well as macrophage-colony stimulating factor (M-CSF). Recent studies have unveiled the precise molecular mechanism underlying osteoclastogenesis. In particular, the discovery of nuclear factor of activated T cells c1 (NFATc1), the master regulator of osteoclastogenesis, has proven to be a breakthrough in this field. NFATc1 is activated by Ca2+ signaling induced by the activation of the immunoglobulin-like receptor signaling associated with immunoreceptor tyrosine-based activation motif (ITAM)-harboring adapters. The long-lasting Ca2+ oscillation, which is evident during osteoclastogenesis, may ensure the robust induction of NFATc1 through an autoamplification mechanism. Thus, intracellular Ca2+ is a critical attribute of osteoclastogenic signaling. In addition, osteoclasts are exposed to a very high extracellular Ca2+ concentration ([Ca2+]o) in the bone microenvironment and respond to the change in [Ca2+]o by increasing the intracellular Ca2+, which regulates diverse cellular functions. Investigation of the molecular mechanisms underlying the regulation of intracellular Ca2+ dynamics may open up new directions for therapeutic strategies in bone disease.
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                Author and article information

                Contributors
                amarjot.singh@mail.mcgill.ca
                Journal
                Prog Orthod
                Prog Orthod
                Progress in Orthodontics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1723-7785
                2196-1042
                25 June 2018
                25 June 2018
                2018
                : 19
                : 18
                Affiliations
                [1 ]ISNI 0000 0004 1936 8649, GRID grid.14709.3b, Faculty of Dentistry, , McGill University, ; Montreal, Quebec Canada
                [2 ]ISNI 0000 0004 1771 1642, GRID grid.412572.7, Department of Endodontics, , Government Dental College, ; Amritsar, Punjab India
                [3 ]ISNI 0000 0000 9401 2774, GRID grid.414980.0, Lady Davis Institute, Jewish General Hospital, ; Montreal, Quebec Canada
                [4 ]Sandalwood Smiles, Private Dental Practice, Brampton, Ontario Canada
                Author information
                http://orcid.org/0000-0002-6073-5346
                Article
                216
                10.1186/s40510-018-0216-2
                6015792
                29938297
                69e9f7f5-e800-4c72-b02b-cf8e9e407ed3
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 27 February 2018
                : 24 May 2018
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                osteopontin,bone remodeling,biomarkers,root resorption,orthodontic tooth movement

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