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      Changes in Serum Levels of Myokines and Wnt-Antagonists after an Ultramarathon Race

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          Abstract

          Background

          Regular physical activities have a positive effect on the muscular skeletal system but overstrenuous exercise may be different. Transiently suppressed bone formation and increased bone resorption after participation in a 246-km ultradistance race has been demonstrated.

          Purpose

          The aim of this study was to analyze effects of the Spartathlon race on novel musculoskeletal markers.

          Methods

          Venous blood samples were obtained before and immediately after the race from 19 participants of the Spartathlon. From 9 runners who were available 3 days after the start blood was drawn for a third time. Serum levels of myostatin, an inhibitor of myogenic differentiation, and its opponent follistatin as well as sclerostin and dickkopf-1, both of them inhibitors of the wnt signaling pathway, and markers of bone turnover were determined.

          Results

          Serum levels of myostatin were significantly higher after the race. Serum follistatin only showed a transient increase. Sclerostin levels did not significantly differ before and after the race, whereas dickkopf-1 levels were significantly decreased. At follow-up a decrement of sclerostin and dickkopf-1 levels was seen. Serum cathepsin K levels did not change.

          Conclusion

          The increase of serum levels of myostatin appears to reflect muscle catabolic processes induced by overstrenuous exercise. After the short-term uncoupling of bone turnover participation in an ultradistance race seems to initiate a long-term positive effect on bone indicated by the low-level inhibition of the Wnt/β-catenin signaling pathway.

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          Most cited references30

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          Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases.

          The processes of bone growth, modeling, and remodeling determine the structure, mass, and biomechanical properties of the skeleton. Dysregulated bone resorption or bone formation may lead to metabolic bone diseases. The Wnt pathway plays an important role in bone formation and regeneration, and expression of two Wnt pathway inhibitors, sclerostin and Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of sclerostin leads to substantially increased bone mass in humans and in genetically manipulated animals. Studies in various animal models of bone disease have shown that inhibition of sclerostin using a monoclonal antibody (Scl-Ab) increases bone formation, density, and strength. Additional studies show that Scl-Ab improves bone healing in models of bone repair. Inhibition of DKK1 by monoclonal antibody (DKK1-Ab) stimulates bone formation in younger animals and to a lesser extent in adult animals and enhances fracture healing. Thus, sclerostin and DKK1 are emerging as the leading new targets for anabolic therapies to treat bone diseases such as osteoporosis and for bone repair. Clinical trials are ongoing to evaluate the effects of Scl-Ab and DKK1-Ab in humans for the treatment of bone loss and for bone repair.
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            Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults.

            Sclerostin is produced by osteocytes and inhibits bone formation through the Wnt/β-catenin-signaling pathway. Only limited data are available on circulating sclerostin levels in healthy subjects. We aimed to evaluate the correlation between sclerostin and physical activity, anthropometric, and biochemical variables. We conducted a cross-sectional observational study in 161 healthy adult men and premenopausal women aged 19 to 64 yr (mean age, 44 ± 10). There were no interventions. Serum sclerostin levels were associated with body composition, bone mineral density, physical activity, and various biochemical parameters. A positive correlation between age and sclerostin in both men (r = 0.37; P < 0.001) and premenopausal women (r = 0.66; P < 0.001) was found. Men had significantly higher sclerostin levels than women (49.8 ± 17.6 vs. 37.2 ± 15.2 pmol/liter; P < 0.001). However, after adjustment for age, bone mineral content (BMC), physical activity, body mass index (BMI), and renal function, sclerostin levels did not differ (P = 0.543). Partial correlation analysis adjusted for age, gender, and kidney function revealed a significant positive correlation between sclerostin levels and BMC, bone mineral density, BMI, and android/gynoid fat and a significant negative correlation with serum osteocalcin and calcium. The most physically active quartile had significantly lower sclerostin levels compared to the least active quartile in a univariate analysis. In healthy adults, sclerostin serum levels correlate positively with age, BMI, and BMC and negatively with osteocalcin and calcium. Further studies in larger populations are needed to confirm our findings and to better understand their clinical implications.
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              Cathepsin K: its skeletal actions and role as a therapeutic target in osteoporosis.

              Bone remodeling consists of two phases--bone resorption and bone formation--that are normally balanced. When bone resorption exceeds bone formation, pathologic processes, such as osteoporosis, can result. Cathepsin K is a member of the papain family of cysteine proteases that is highly expressed by activated osteoclasts. Cathepsin K readily degrades type I collagen, the major component of the organic bone matrix. With such a major role in the initial process of bone resorption, cathepsin K has become a therapeutic target in osteoporosis. The antiresorptive properties of cathepsin K inhibitors have been studied in phase I and phase II clinical trials. Phase III studies are currently underway for odanacatib, a selective cathepsin K inhibitor.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 July 2015
                2015
                : 10
                : 7
                : e0132478
                Affiliations
                [1 ]Department of Physical Medicine and Rehabilitation, Medical University of Vienna, Vienna, Austria
                [2 ]Department of Cardiovascular Surgery, Hospital Hietzing, Vienna, Austria
                [3 ]Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
                [4 ]School of Nursing, University of Peloponnese, Sparta, Greece
                [5 ]Karl Landsteiner Institute for Cardiovascular Surgical Research, Vienna, Austria
                [6 ]Department of Nutrition and Dietetics, Harokopio University, Athens, Greece
                University of Birmingham, UNITED KINGDOM
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: KKS MMT UFS JM KS PP. Performed the experiments: MMT MT KS. Analyzed the data: KKS MMT EW UFS JM KS PP. Contributed reagents/materials/analysis tools: EW UFS PP. Wrote the paper: KKS UFS PP.

                Article
                PONE-D-15-11440
                10.1371/journal.pone.0132478
                4493015
                26147574
                32831aac-ceed-4529-947b-63a6f0a7540c
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 18 March 2015
                : 15 June 2015
                Page count
                Figures: 1, Tables: 2, Pages: 10
                Funding
                This work was supported by the following grants: Austrian Society of Rheumatology and Rheumatic Diseases and the Karl Landsteiner Institute for Cardiovascular Surgical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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