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      Nidogen: A matrix protein with potential roles in musculoskeletal tissue regeneration

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          Abstract

          Basement membrane proteins are known to guide cell structures, differentiation, and tissue repair. Although there is a wealth of knowledge on the functions of laminins, perlecan, and type IV collagen in maintaining tissue homeostasis, not much is known about nidogen. As a key molecule in the basement membrane, nidogen contributes to the formation of a delicate microenvironment that proves necessary for stem cell lineage-specific differentiation. In this review, the expression of nidogen is delineated at both cellular and tissue levels from embryonic to adult stages of development; the effect of nidogens is also summarized in the context of musculoskeletal development and regeneration, including but not limited to adipogenesis, angiogenesis, chondrogenesis, myogenesis, and neurogenesis. Furthermore, potential mechanisms underlying the role of nidogens in stem cell-based tissue regeneration are also discussed. This concise review is expected to facilitate our existing understanding and utilization of nidogen in tissue engineering and regeneration.

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          Most cited references140

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          Matrix elasticity directs stem cell lineage specification.

          Microenvironments appear important in stem cell lineage specification but can be difficult to adequately characterize or control with soft tissues. Naive mesenchymal stem cells (MSCs) are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. Soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. During the initial week in culture, reprogramming of these lineages is possible with addition of soluble induction factors, but after several weeks in culture, the cells commit to the lineage specified by matrix elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types. Inhibition of nonmuscle myosin II blocks all elasticity-directed lineage specification-without strongly perturbing many other aspects of cell function and shape. The results have significant implications for understanding physical effects of the in vivo microenvironment and also for therapeutic uses of stem cells.
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            The basics of epithelial-mesenchymal transition.

            The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
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              The extracellular matrix: not just pretty fibrils.

              The extracellular matrix (ECM) and ECM proteins are important in phenomena as diverse as developmental patterning, stem cell niches, cancer, and genetic diseases. The ECM has many effects beyond providing structural support. ECM proteins typically include multiple, independently folded domains whose sequences and arrangement are highly conserved. Some of these domains bind adhesion receptors such as integrins that mediate cell-matrix adhesion and also transduce signals into cells. However, ECM proteins also bind soluble growth factors and regulate their distribution, activation, and presentation to cells. As organized, solid-phase ligands, ECM proteins can integrate complex, multivalent signals to cells in a spatially patterned and regulated fashion. These properties need to be incorporated into considerations of the functions of the ECM.
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                Author and article information

                Contributors
                Journal
                Genes Dis
                Genes Dis
                Genes & Diseases
                Chongqing Medical University
                2352-4820
                2352-3042
                02 April 2021
                May 2022
                02 April 2021
                : 9
                : 3
                : 598-609
                Affiliations
                [a ]Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506, USA
                [b ]Department of Orthopaedics, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, PR China
                [c ]WVU Cancer Institute, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506, USA
                Author notes
                []Corresponding author. Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, PO Box 9196, 64 Medical Center Drive, Morgantown, WV 26506-9196, USA. Fax: +304 293 7070. mpei@ 123456hsc.wvu.edu
                [1]

                Co-first authors.

                Article
                S2352-3042(21)00043-X
                10.1016/j.gendis.2021.03.004
                9243345
                35782975
                f1f6977d-7528-4488-ab32-77c42817be3f
                © 2021 Chongqing Medical University. Production and hosting by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 11 January 2021
                : 3 March 2021
                : 24 March 2021
                Categories
                Review Article

                adipose,basement membrane,cartilage,differentiation,nerve,nidogens,vessel

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