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      Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment

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          Abstract

          Osteoporosis is a progressive skeletal disease characterized by decreased bone mass and degraded bone microstructure, which leads to increased bone fragility and risks of bone fracture. Osteoporosis is generally age related and has become a major disease of the world. Uncovering the molecular mechanisms underlying osteoporosis and developing effective prevention and therapy methods has great significance for human health. Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into osteoblasts, adipocytes, or chondrocytes, and have become the favorite source of cell-based therapy. Evidence shows that during osteoporosis, a shift of the cell differentiation of MSCs to adipocytes rather than osteoblasts partly contributes to osteoporosis. Thus, uncovering the molecular mechanisms of the osteoblast or adipocyte differentiation of MSCs will provide more understanding of MSCs and perhaps new methods of osteoporosis treatment. The MSCs have been applied to both preclinical and clinical studies in osteoporosis treatment. Here, we review the recent advances in understanding the molecular mechanisms regulating osteoblast differentiation and adipocyte differentiation of MSCs and highlight the therapeutic application studies of MSCs in osteoporosis treatment. This will provide researchers with new insights into the development and treatment of osteoporosis.

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          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.
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            Concise review: the surface markers and identity of human mesenchymal stem cells.

            The concept of mesenchymal stem cells (MSCs) is becoming increasingly obscure due to the recent findings of heterogeneous populations with different levels of stemness within MSCs isolated by traditional plastic adherence. MSCs were originally identified in bone marrow and later detected in many other tissues. Currently, no cloning based on single surface marker is capable of isolating cells that satisfy the minimal criteria of MSCs from various tissue environments. Markers that associate with the stemness of MSCs await to be elucidated. A number of candidate MSC surface markers or markers possibly related to their stemness have been brought forward so far, including Stro-1, SSEA-4, CD271, and CD146, yet there is a large difference in their expression in various sources of MSCs. The exact identity of MSCs in vivo is not yet clear, although reports have suggested they may have a fibroblastic or pericytic origin. In this review, we revisit the reported expression of surface molecules in MSCs from various sources, aiming to assess their potential as MSC markers and define the critical panel for future investigation. We also discuss the relationship of MSCs to fibroblasts and pericytes in an attempt to shed light on their identity in vivo. © 2014 AlphaMed Press.
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              THE DEVELOPMENT OF FIBROBLAST COLONIES IN MONOLAYER CULTURES OF GUINEA-PIG BONE MARROW AND SPLEEN CELLS

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                25 January 2018
                February 2018
                : 19
                : 2
                : 360
                Affiliations
                [1 ]Laboratory for Bone Metabolism, Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China; hulifang@ 123456nwpu.edu.cn (L.H.); yinchong42@ 123456mail.nwpu.edu.cn (C.Y.); sofan@ 123456mail.nwpu.edu.cn (F.Z.); ArshadAli@ 123456mail.nwpu.edu.cn (A.A.); majianhua@ 123456mail.nwpu.edu.cn (J.M.)
                [2 ]School of Public Health, Lanzhou University, Lanzhou 730000, China
                Author notes
                [* ]Correspondence: qianair@ 123456nwpu.edu.cn ; Tel.: +86-29-8849-1840
                Author information
                https://orcid.org/0000-0003-1648-4428
                https://orcid.org/0000-0002-0740-9218
                Article
                ijms-19-00360
                10.3390/ijms19020360
                5855582
                29370110
                1cdf54e9-ec81-4cb6-8bab-1b8c2327ba8e
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 December 2017
                : 22 January 2018
                Categories
                Review

                Molecular biology
                osteoporosis,mesenchymal stem cell,osteoblast,adipocyte,cell therapy
                Molecular biology
                osteoporosis, mesenchymal stem cell, osteoblast, adipocyte, cell therapy

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