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      Evaluation of the Bone Regeneration Effect of Recombinant Human Bone Morphogenic Protein-2 on Subperiosteal Bone Graft in the Rat Calvarial Model

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          Abstract

          The aim of this study was to evaluate the bone regeneration effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on a subperiosteal bone graft in a rat model. A subperiosteal space was made on the rat calvarium, and anorganic bovine bone (ABB), ABB/low bone morphogenetic protein (BMP) (5 µg), and ABB/high BMP (50 µg) were grafted as subperiosteal bone grafts. The new bone formation parameters of bone volume (BV), bone mineral density (BMD), trabecular thickness (TbTh), and trabecular spacing (TbSp) were evaluated by microcomputed tomography (µ-CT), and a histomorphometric analysis was performed to evaluate the new bone formation area. The expression of osteogenic markers, such as bone sialoprotein (BSP) and osteocalcin, were evaluated by immunohistochemistry (IHC). The ABB/high BMP group showed significantly higher BV than the ABB/low BMP ( p = 0.004) and control groups ( p = 0.000) and higher TbTh than the control group ( p = 0.000). The ABB/low BMP group showed significantly higher BV, BMD, and TbTh than the control group ( p = 0.002, 0.042, and 0.000, respectively). The histomorphometry showed significantly higher bone formation in the ABB/low and high BMP groups than in the control group ( p = 0.000). IHC showed a high expression of BSP and osteocalcin in the ABB/low and high BMP groups. Subperiosteal bone grafts with ABB and rhBMP-2 have not been studied. In our study, we confirmed that rhBMP-2 contributes to new bone formation in a subperiosteal bone graft with ABB.

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          Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells.

          Efficacious bone regeneration could revolutionize the clinical management of many bone and musculoskeletal disorders. Bone morphogenetic proteins (BMPs) can regulate the differentiation of mesenchymal stem cells into cartilage, bone, tendon/ligament, and fat lineages. Early data documented the osteogenic potential of rhBMP2 and rhBMP7/OP-1. However, prior to this work that summarized several of our recent studies, no comprehensive analysis had been undertaken to characterize relative osteogenic activity of all BMPs. Using recombinant adenoviruses expressing 14 BMPs, we have demonstrated that, besides BMP2 and BMP7, BMP6 and BMP9 exhibit the highest osteogenic activity both in vitro and in vivo. We further demonstrated that several BMPs may exert synergistic effect on osteogenic differentiation, and that osteogenic BMPs produce a distinct set of molecular fingerprints during osteogenic differentiation. The reported work should expand our current understanding of BMP functions during osteogenic differentiation. It is conceivable that osteogenic BMPs (i.e., BMP2, 4, 6, 7, and 9) may be used to formulate synergistic pairs among themselves and/or with other less osteogenic BMPs for efficacious bone regeneration in clinical settings. (c) 2007 Orthopaedic Research Society.
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            Bone morphogenetic proteins: facts, challenges, and future perspectives.

            Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily, acting as potent regulators during embryogenesis and bone and cartilage formation and repair. Cell and molecular biology approaches have unveiled the great complexity of BMP action, later confirmed by transgenic animal studies. Genetic engineering allows for the production of large amounts of BMPs for clinical use, but they have systematically been associated with a delivery system, such as type I collagen and calcium phosphate ceramics, to ensure controlled release and to maximize their biological activity at the surgical site, avoiding systemic diffusion. Clinical orthopedic studies have shown the benefits of FDA-approved recombinant human BMPs (rhBMPs) 2 and 7, but side effects, such as swelling, seroma, and increased cancer risk, have been reported, probably due to high BMP dosage. Several studies have supported the use of BMPs in periodontal regeneration, sinus lift bone-grafting, and non-unions in oral surgery. However, the clinical use of BMPs is growing mainly in off-label applications, with robust evidence to ascertain rhBMPs' safety and efficacy through well-designed, randomized, and double-blind clinical trials. Here we review and discuss the critical data on BMP structure, mechanisms of action, and possible clinical applications.
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              Periosteum: biology, regulation, and response to osteoporosis therapies.

              Periosteum contains osteogenic cells that regulate the outer shape of bone and work in coordination with inner cortical endosteum to regulate cortical thickness and the size and position of a bone in space. Induction of periosteal expansion, especially at sites such as the lumbar spine and femoral neck, reduces fracture risk by modifying bone dimensions to increase bone strength. The cell and molecular mechanisms that selectively and specifically activate periosteal expansion, as well as the mechanisms by which osteoporosis drugs regulate periosteum, remain poorly understood. We speculate that an alternate strategy to protect human bones from fracture may be through targeting of the periosteum, either using current or novel agents. In this review, we highlight current concepts of periosteal cell biology, including their apparent differences from endosteal osteogenic cells, discuss the limited data regarding how the periosteal surface is regulated by currently approved osteoporosis drugs, and suggest one potential means through which targeting periosteum may be achieved. Improving our understanding of mechanisms controlling periosteal expansion will likely provide insights necessary to enhance current and develop novel interventions to further reduce the risk of osteoporotic fractures.
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                Author and article information

                Journal
                Materials (Basel)
                Materials (Basel)
                materials
                Materials
                MDPI
                1996-1944
                16 May 2019
                May 2019
                : 12
                : 10
                : 1613
                Affiliations
                [1 ]Department of Orthodontics, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Korea; jianejiane@ 123456naver.com
                [2 ]Department of Prosthodontics, Chungbuk National University Hospital, Cheongju 28644, Korea; jayoun.lee@ 123456gmail.com
                [3 ]Department of Oral and Maxillofacial Surgery, Chungbuk National University College of Medicine, Cheongju 28644, Korea; ley926@ 123456chungbuk.ac.kr
                [4 ]Department of Oral and Maxillofacial Surgery, Chungbuk National University Hospital, Cheongju 28644, Korea
                Author notes
                [* ]Correspondence: sok8585@ 123456hanmail.net ; Tel.: +82-43-269-6387
                Author information
                https://orcid.org/0000-0002-5278-3807
                Article
                materials-12-01613
                10.3390/ma12101613
                6566192
                31100907
                8074689a-b300-4fbe-a63b-3883220152cf
                © 2019 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
                : 02 May 2019
                : 13 May 2019
                Categories
                Article

                bone morphogenetic protein,bone regeneration,subperiosteal bone graft,bone sialoprotein,osteocalcin

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