23
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The wonders of BMP9: From mesenchymal stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism to regenerative medicine

      review-article
      a , b , a , b , a , b , a , b , d , a , c , c , c , c , b , c , c , e , c , c , c , c , e , c , e , c , e , c , c , c , c , f , g , c , c , c , c , c , ∗∗ , b ,
      Genes & Diseases
      Chongqing Medical University
      Adipogenesis, Bone morphogenetic proteins (BMPs), BMP9/GDF2, Mesenchymal stem cells (MSCs), Metabolism, Osteogenesis, Regenerative medicine, Tumorigenesis

      Read this article at

      ScienceOpenPublisherPMC
      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

          Although bone morphogenetic proteins (BMPs) initially showed effective induction of ectopic bone growth in muscle, it has since been determined that these proteins, as members of the TGF-β superfamily, play a diverse and critical array of biological roles. These roles include regulating skeletal and bone formation, angiogenesis, and development and homeostasis of multiple organ systems. Disruptions of the members of the TGF-β/BMP superfamily result in severe skeletal and extra-skeletal irregularities, suggesting high therapeutic potential from understanding this family of BMP proteins. Although it was once one of the least characterized BMPs, BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo, with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs. The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants, revealing the great translational promise of BMP9. Furthermore, emerging evidence indicates that, besides its osteogenic activity, BMP9 exerts a broad range of biological functions, including stem cell differentiation, angiogenesis, neurogenesis, tumorigenesis, and metabolism. This review aims to summarize our current understanding of BMP9 across biology and the body.

          Related collections

          Most cited references187

          • Record: found
          • Abstract: found
          • Article: not found

          Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone.

          The mammalian skeletal system harbours a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in ageing organisms, leading to loss of bone mass and increased fracture incidence. Evidence indicates that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanisms. Here we identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are found in specific locations, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, and pharmacological reversal of this decline allowed the restoration of bone mass.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            TGF-beta signal transduction.

            The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.
              Bookmark
              • 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

                Author and article information

                Contributors
                Journal
                Genes Dis
                Genes Dis
                Genes & Diseases
                Chongqing Medical University
                2352-4820
                2352-3042
                24 July 2019
                September 2019
                24 July 2019
                : 6
                : 3
                : 201-223
                Affiliations
                [a ]The University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA
                [b ]Laboratory of Craniofacial Biology and Development, Section of Plastic and Reconstructive Surgery, Department of Surgery, The University of Chicago Medicine, Chicago, IL 60637, USA
                [c ]Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA
                [d ]Rosalind Franklin University, Chicago Medical School, North Chicago, IL 60064, USA
                [e ]SIR Program, Illinois Math and Science Academy (IMSA), Aurora, IL 60506, USA
                [f ]Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA
                [g ]The Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60616, USA
                Author notes
                []Corresponding author. Section of Plastic and Reconstructive Surgery, Department of Surgery, The University of Chicago Medical Center, Chicago, IL, 60637, USA. Fax: +773 702 1634. rreid@ 123456surgery.bsd.uchicago.edu
                [∗∗ ]Corresponding author. Molecular Oncology Laboratory, The University of Chicago Medical Center, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637, USA. Fax: +773 834 4598. tche@ 123456uchicago.edu
                Article
                S2352-3042(19)30046-7
                10.1016/j.gendis.2019.07.003
                6997590
                32042861
                109113a9-d893-4695-8e0b-10a5190d12ff
                © 2019 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
                : 7 June 2019
                : 7 July 2019
                : 10 July 2019
                Categories
                Article

                adipogenesis,bone morphogenetic proteins (bmps),bmp9/gdf2,mesenchymal stem cells (mscs),metabolism,osteogenesis,regenerative medicine,tumorigenesis

                Comments

                Comment on this article