85
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Transforming Growth Factor Beta Family: Insight into the Role of Growth Factors in Regulation of Fracture Healing Biology and Potential Clinical Applications

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The transforming growth factor beta (TGF- β) family forms a group of three isoforms, TGF- β1, TGF- β2, and TGF- β3, with their structure formed by interrelated dimeric polypeptide chains. Pleiotropic and redundant functions of the TGF- β family concern control of numerous aspects and effects of cell functions, including proliferation, differentiation, and migration, in all tissues of the human body. Amongst many cytokines and growth factors, the TGF- β family is considered a group playing one of numerous key roles in control of physiological phenomena concerning maintenance of metabolic homeostasis in the bone tissue. By breaking the continuity of bone tissue, a spread-over-time and complex bone healing process is initiated, considered a recapitulation of embryonic intracartilaginous ossification. This process is a cascade of local and systemic phenomena spread over time, involving whole cell lineages and various cytokines and growth factors. Numerous in vivo and in vitro studies in various models analysing cytokines and growth factors' involvement have shown that TGF- β has a leading role in the fracture healing process. This paper sums up current knowledge on the basis of available literature concerning the role of the TGF- β family in the fracture healing process.

          Related collections

          Most cited references232

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation

          Transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-β/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-β/BMPs is specifically through both canonical Smad-dependent pathways (TGF-β/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-β/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-β/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-β/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-β/BMP signaling. This review also highlights the different modes of cross-talk between TGF-β/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Fracture healing under healthy and inflammatory conditions.

            Optimal fracture treatment requires knowledge of the complex physiological process of bone healing. The course of bone healing is mainly influenced by fracture fixation stability (biomechanics) and the blood supply to the healing site (revascularization after trauma). The repair process proceeds via a characteristic sequence of events, described as the inflammatory, repair and remodeling phases. An inflammatory reaction involving immune cells and molecular factors is activated immediately in response to tissue damage and is thought to initiate the repair cascade. Immune cells also have a major role in the repair phase, exhibiting important crosstalk with bone cells. After bony bridging of the fragments, a slow remodeling process eventually leads to the reconstitution of the original bone structure. Systemic inflammation, as observed in patients with rheumatoid arthritis, diabetes mellitus, multiple trauma or sepsis, can increase fracture healing time and the rate of complications, including non-unions. In addition, evidence suggests that insufficient biomechanical conditions within the fracture zone can influence early local inflammation and impair bone healing. In this Review, we discuss the main factors that influence fracture healing, with particular emphasis on the role of inflammation.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Integrin structure, activation, and interactions.

              Integrins are large, membrane-spanning, heterodimeric proteins that are essential for a metazoan existence. All members of the integrin family adopt a shape that resembles a large "head" on two "legs," with the head containing the sites for ligand binding and subunit association. Most of the receptor dimer is extracellular, but both subunits traverse the plasma membrane and terminate in short cytoplasmic domains. These domains initiate the assembly of large signaling complexes and thereby bridge the extracellular matrix to the intracellular cytoskeleton. To allow cells to sample and respond to a dynamic pericellular environment, integrins have evolved a highly responsive receptor activation mechanism that is regulated primarily by changes in tertiary and quaternary structure. This review summarizes recent progress in the structural and molecular functional studies of this important class of adhesion receptor.
                Bookmark

                Author and article information

                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi Publishing Corporation
                0962-9351
                1466-1861
                2015
                29 January 2015
                : 2015
                : 137823
                Affiliations
                1Department of General and Experimental Pathology with Centre for Preclinical Research and Technology (CePT), Second Faculty of Medicine, Medical University of Warsaw, Pawińskiego 3c, 02-106 Warsaw, Poland
                2Department of Rheumaorthopaedics, Institute of Rheumatology, Spartańska 1, 02-637 Warsaw, Poland
                3Department of Neuroorthopaedics and Neurology, Institute of Rheumatology, Spartańska 1, 02-637 Warsaw, Poland
                Author notes
                *Dariusz Szukiewicz: dszukiewicz@ 123456hotmail.com

                Academic Editor: Philip Stahel

                Author information
                http://orcid.org/0000-0003-3309-996X
                http://orcid.org/0000-0002-0124-060X
                Article
                10.1155/2015/137823
                4325469
                25709154
                9807d063-6bcf-435f-a0aa-21a543b32e88
                Copyright © 2015 Łukasz A. Poniatowski et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 September 2014
                : 9 November 2014
                Categories
                Review Article

                Immunology
                Immunology

                Comments

                Comment on this article