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      Role of Wnt5a in periodontal tissue development, maintenance, and periodontitis: Implications for periodontal regeneration

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          Abstract

          The periodontium is a highly dynamic microenvironment constantly adapting to changing external conditions. In the processes of periodontal tissue formation and remodeling, certain molecules may serve an essential role in maintaining periodontal homeostasis. Wnt family member 5a (Wnt5a), as a member of the Wnt family, has been identified to have extensive biological roles in development and disease, predominantly through the non-canonical Wnt signaling pathway or through interplay with the canonical Wnt signaling pathway. An increasing number of studies has also demonstrated that it serves crucial roles in periodontal tissues. Wnt5a participates in the development of periodontal tissues, maintains a non-mineralized state of periodontal ligament, and regulates bone homeostasis. In addition, Wnt5a is involved in the pathogenesis of periodontitis. Recently, it has been shown to serve a positive role in the regeneration of integrated periodontal complex. The present review article focuses on recent research studies of Wnt5a and its functions in development, maintenance, and pathological disorders of periodontal tissues, as well as its potential effect on periodontal regeneration.

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          Most cited references69

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          Wnt/Ca2+ signaling pathway: a brief overview.

          Antara De (2011)
          The non-canonical Wnt/Ca(2+) signaling cascade is less characterized than their canonical counterpart, the Wnt/β-catenin pathway. The non-canonical Wnt signaling pathways are diverse, defined as planer cell polarity pathway, Wnt-RAP1 signaling pathway, Wnt-Ror2 signaling pathway, Wnt-PKA pathway, Wnt-GSK3MT pathway, Wnt-aPKC pathway, Wnt-RYK pathway, Wnt-mTOR pathway, and Wnt/calcium signaling pathway. All these pathways exhibit a considerable degree of overlap between them. The Wnt/Ca(2+) signaling pathway was deciphered as a crucial mediator in development. However, now there is substantial evidence that the signaling cascade is involved in many other molecular phenomena. Many aspects of Wnt/Ca(2+) pathway are yet enigmatic. This review will give a brief overview of the fundamental and evolving concepts of the Wnt/Ca(2+) signaling pathway.
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            A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo.

            Morphogenesis depends on the precise control of basic cellular processes such as cell proliferation and differentiation. Wnt5a may regulate these processes since it is expressed in a gradient at the caudal end of the growing embryo during gastrulation, and later in the distal-most aspect of several structures that extend from the body. A loss-of-function mutation of Wnt5a leads to an inability to extend the A-P axis due to a progressive reduction in the size of caudal structures. In the limbs, truncation of the proximal skeleton and absence of distal digits correlates with reduced proliferation of putative progenitor cells within the progress zone. However, expression of progress zone markers, and several genes implicated in distal outgrowth and patterning including Distalless, Hoxd and Fgf family members was not altered. Taken together with the outgrowth defects observed in the developing face, ears and genitals, our data indicates that Wnt5a regulates a pathway common to many structures whose development requires extension from the primary body axis. The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells.
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              Planar cell polarity in development and disease

              Planar cell polarity — the asymmetric distribution of proteins in the plane of a cell sheet — dictates the orientation of various subcellular structures and drives collective cell rearrangements. Better understanding of this conserved axis of polarity can shed light on the mechanisms of morphogenetic processes and explain the underlying causes of human birth defects.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                March 2021
                23 December 2020
                23 December 2020
                : 23
                : 3
                : 167
                Affiliations
                [1 ]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China
                [2 ]National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China
                [3 ]Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China
                Author notes
                Correspondence to: Professor Yafei Wu or Dr Shujuan Guo, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, 14 Renmin South Road (3rd Sect), Chengdu, Sichuan 610041, P.R. China, E-mail: yfw1110@ 123456163.com , E-mail: guo.shujuan@ 123456yahoo.com
                Article
                MMR-0-0-11806
                10.3892/mmr.2020.11806
                7821221
                33398377
                f7b39a00-1c03-4b08-b7ca-4c4d56be601a
                Copyright: © Wei et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 02 September 2020
                : 25 November 2020
                Categories
                Review

                wnt family member 5a,periodontium,periodontal homeostasis,periodontitis,periodontal regeneration

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