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      Bone regeneration and stem cells

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          Abstract

          This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.

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          Most cited references244

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          Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis.

          Chondrocytes and osteoblasts are two primary cell types in the skeletal system that are differentiated from common mesenchymal progenitors. It is believed that osteoblast differentiation is controlled by distinct mechanisms in intramembranous and endochondral ossification. We have found that ectopic canonical Wnt signaling leads to enhanced ossification and suppression of chondrocyte formation. Conversely, genetic inactivation of beta-catenin, an essential component transducing the canonical Wnt signaling, causes ectopic formation of chondrocytes at the expense of osteoblast differentiation during both intramembranous and endochondral ossification. Moreover, inactivation of beta-catenin in mesenchymal progenitor cells in vitro causes chondrocyte differentiation under conditions allowing only osteoblasts to form. Our results demonstrate that beta-catenin is essential in determining whether mesenchymal progenitors will become osteoblasts or chondrocytes regardless of regional locations or ossification mechanisms. Controlling Wnt/beta-catenin signaling is a common molecular mechanism underlying chondrocyte and osteoblast differentiation and specification of intramembranous and endochondral ossification.
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            Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development.

            The potential to generate virtually any differentiated cell type from embryonic stem cells (ESCs) offers the possibility to establish new models of mammalian development and to create new sources of cells for regenerative medicine. To realize this potential, it is essential to be able to control ESC differentiation and to direct the development of these cells along specific pathways. Embryology has offered important insights into key pathways regulating ESC differentiation, resulting in advances in modeling gastrulation in culture and in the efficient induction of endoderm, mesoderm, and ectoderm and many of their downstream derivatives. This has led to the identification of new multipotential progenitors for the hematopoietic, neural, and cardiovascular lineages and to the development of protocols for the efficient generation of a broad spectrum of cell types including hematopoietic cells, cardiomyocytes, oligodendrocytes, dopamine neurons, and immature pancreatic beta cells. The next challenge will be to demonstrate the functional utility of these cells, both in vitro and in preclinical models of human disease.
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              Control of osteoblast function and regulation of bone mass.

              The skeleton is an efficient 'servo' (feedback-controlled/steady-state) system that continuously integrates signals and responses which sustain its functions of delivering calcium while maintaining strength. In many individuals, bone mass homeostasis starts failing in midlife, leading to bone loss, osteoporosis and debilitating fractures. Recent advances, spearheaded by genetic information, offer the opportunity to stop or reverse this downhill course.
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                Author and article information

                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                jcmm
                Journal of Cellular and Molecular Medicine
                Blackwell Publishing Ltd (Oxford, UK )
                1582-1838
                1582-4934
                April 2011
                06 May 2011
                : 15
                : 4
                : 718-746
                Affiliations
                [a ]Department of Clinical Dentistry, Center for Clinical Resarch, Faculty of Medicine and Dentistry, University of Bergen Bergen, Norway
                [b ]Department of Endocrinology, Molecular Endocrinology Laboratory, Odense University Hospital & Medical Biotechnology Centre, University of Southern Denmark Odense, Denmark
                [c ]Department of Musculoskeletal Medicine, Service of Plastic and Reconstructive Surgery, Cellular Therapy Unit, University Hospital of Lausanne Lausanne, Switzerland
                [d ]Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli Bologna, Italy
                [e ]Servicio de Cirugìa Ortopédica y Traumatologìa, Hospital, Universitario ‘La Paz’, Universidad Autónoma de Madrid Madrid, Spain
                [f ]Department of Anatomy, Stem Cell Unit, College of Medicine, King Saud University Riyadh, Saudi Arabia
                [g ]Department of Medicine, Helsinki University Central Hospital Helsinki, Finland
                [h ]ORTON Orthopaedic Hospital, ORTON Foundation Helsinki, Finland
                [i ]COXA Hospital for Joint Replacement Tampere, Finland
                [k ]Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, Ecole Polytechnique Fédérale Lausanne Lausanne, Switzerland
                [l ]Royal Institute of Technology, Fibre and Polymer Technology, School of Chemical Science and Engineering Stockholm, Sweden
                Author notes
                Correspondence to: Prof. Kristina ARVIDSON, Department of Clinical Dentistry, Årstadsv.17, 5009 Bergen, Norway. Tel.: +46707368988 Fax: +468858140 E-mail: kristina.arvidson@ 123456iko.uib.no
                Article
                10.1111/j.1582-4934.2010.01224.x
                3922662
                21129153
                6ad86541-ed9e-43ab-b890-3eb4b056fd5a
                © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
                History
                : 07 August 2010
                : 02 November 2010
                Categories
                Reviews

                Molecular medicine
                bone regeneration,stem cells,biomaterials,polymers,regenerative medicine
                Molecular medicine
                bone regeneration, stem cells, biomaterials, polymers, regenerative medicine

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