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      The Irisin Hormone Profile and Expression in Human Bone Tissue in the Bone Healing Process in Patients

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          Abstract

          Background

          Whether or not there is a relationship between the newly-discovered irisin hormone and bone healing is not yet known. The aim of this study was to investigate what effect irisin hormone has on the bone healing process.

          Material/Methods

          The study included 21 adult patients with a diagnosed fracture of the lower extremity (femur or tibia). Informed consent was obtained from all the patients. A total of four venous blood samples were taken from the patients: before fracture stabilization, then postoperatively on days 1, 10, and 60. In patients with femoral neck fracture who had hip prosthesis applied, bone tissue samples were taken from the removed femur head and irisin was determined immunohistochemically in muscle biopsies taken from the same patients.

          Results

          In analysis, it was revealed that the mean value of irisin 60 days after operation is significantly higher than the values of irisin before operation, 1 day after operation, and 15 day after operation ( p<0.001, p<0.001, p<0.001, respectively). Intense staining was observed in compact bone tissue, muscle tissue, and in hypertrophic vascular endothelium within the Havers canal.

          Conclusions

          The level of irisin hormone increased in the bone union process and affects fracture healing due to irisin receptors in human bone tissue.

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          Most cited references27

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          A PGC1α-dependent myokine that drives browning of white fat and thermogenesis

          Pontus Boström, Yao-jun Wu, Mark P. Jedrychowski … (2012)
          Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional coactivator PGC1α Here we show that PGC1α expression in muscle stimulates an increase in expression of Fndc5, a membrane protein that is cleaved and secreted as a new hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be a protein therapeutic for human metabolic disease and other disorders that are improved with exercise.
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            The biology of fracture healing.

            Richard Marsell, Thomas Einhorn (2011)
            The biology of fracture healing is a complex biological process that follows specific regenerative patterns and involves changes in the expression of several thousand genes. Although there is still much to be learned to fully comprehend the pathways of bone regeneration, the over-all pathways of both the anatomical and biochemical events have been thoroughly investigated. These efforts have provided a general understanding of how fracture healing occurs. Following the initial trauma, bone heals by either direct intramembranous or indirect fracture healing, which consists of both intramembranous and endochondral bone formation. The most common pathway is indirect healing, since direct bone healing requires an anatomical reduction and rigidly stable conditions, commonly only obtained by open reduction and internal fixation. However, when such conditions are achieved, the direct healing cascade allows the bone structure to immediately regenerate anatomical lamellar bone and the Haversian systems without any remodelling steps necessary. In all other non-stable conditions, bone healing follows a specific biological pathway. It involves an acute inflammatory response including the production and release of several important molecules, and the recruitment of mesenchymal stem cells in order to generate a primary cartilaginous callus. This primary callus later undergoes revascularisation and calcification, and is finally remodelled to fully restore a normal bone structure. In this article we summarise the basic biology of fracture healing. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              The myokine irisin increases cortical bone mass.

              Graziana Colaianni, Concetta Cuscito, Teresa Mongelli … (2015)
              It is unclear how physical activity stimulates new bone synthesis. We explored whether irisin, a newly discovered myokine released upon physical activity, displays anabolic actions on the skeleton. Young male mice were injected with vehicle or recombinant irisin (r-irisin) at a low cumulative weekly dose of 100 µg kg(-1). We observed significant increases in cortical bone mass and strength, notably in cortical tissue mineral density, periosteal circumference, polar moment of inertia, and bending strength. This anabolic action was mediated primarily through the stimulation of bone formation, but with parallel notable reductions in osteoclast numbers. The trabecular compartment of the same bones was spared, as were vertebrae from the same mice. Higher irisin doses (3,500 µg kg(-1) per week) cause browning of adipose tissue; this was not seen with low-dose r-irisin. Expectedly, low-dose r-irisin modulated the skeletal genes, Opn and Sost, but not Ucp1 or Pparγ expression in white adipose tissue. In bone marrow stromal cell cultures, r-irisin rapidly phosphorylated Erk, and up-regulated Atf4, Runx2, Osx, Lrp5, β-catenin, Alp, and Col1a1; this is consistent with a direct receptor-mediated action to stimulate osteogenesis. We also noted that, although the irisin precursor Fndc5 was expressed abundantly in skeletal muscle, other sites, such as bone and brain, also expressed Fndc5, albeit at low levels. Furthermore, muscle fibers from r-irisin-injected mice displayed enhanced Fndc5 positivity, and irisin induced Fdnc5 mRNA expression in cultured myoblasts. Our data therefore highlight a previously unknown action of the myokine irisin, which may be the molecular entity responsible for muscle-bone connectivity.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Med Sci Monit
                Journal ID (iso-abbrev): Med. Sci. Monit
                Journal ID (publisher-id): Medical Science Monitor
                Title: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                Publisher: International Scientific Literature, Inc.
                ISSN (Print): 1234-1010
                ISSN (Electronic): 1643-3750
                Publication date Collection: 2017
                Publication date (Electronic): 04 September 2017
                Volume: 23
                Pages: 4278-4283
                Affiliations
                [1 ]Department of Orthopedics and Traumatology, Faculty of Medicine, Kirikkale University, Kırıkkale, Turkey
                [2 ]Department of Orthopedics and Traumatology, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey
                [3 ]Department of Biochemistry, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey
                Author notes
                Corresponding Author: Sancar Serbest, e-mail: dr.sancarserbest@ 123456hotmail.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                Publisher ID: 906293
                DOI: 10.12659/MSM.906293
                PMC ID: 5597035
                PubMed ID: 28869754
                SO-VID: 90990432-fa13-464d-90eb-8024ca9595fd
                Copyright © © Med Sci Monit, 2017
                License:

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                Date received : 20 July 2017
                Date accepted : 09 August 2017
                Categories
                Subject: Clinical Research

                Keywords: bone and bones,bone diseases, endocrine,fracture healing
                Data availability:
                Keywords: bone and bones, bone diseases, endocrine, fracture healing

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