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      La osteocalcina: de marcador de formación ósea a hormona; y el hueso, un órgano endocrino Translated title: Osteocalcin: from marker of bone formation to hormone; and bone, an endocrine organ

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          Abstract

          Resumen La osteocalcina es una proteína sintetizada por el osteoblasto. Antes de ser liberada a la matriz extracelular, la osteocalcina humana sufre una gamma-carboxilación, al unirse en las posiciones 17, 21 y 24 el ácido gamma-carboxi-glutámico. A la circulación pasa parte de osteocalcina carboxilada y descarboxilada. Desde su descubrimiento a finales de los años 70, se ha utilizado como marcador de formación ósea al ser un producto osteoblástico, y desconociéndose su papel en el organismo. En estos últimos años se ha descubierto que la osteocalcina es, en realidad, una hormona, y el hueso un órgano endocrino. La osteocalcina que actúa como hormona es la forma descarboxilada. La osteocalcina interviene en la homeostasis de la glucosa, en el funcionamiento del músculo esquelético, en el desarrollo cerebral, la fertilidad masculina, la esteatosis hepática y la calcificación arterial. En realidad todos estos hechos se han probado en ratones, pero existen indicios importantes de que esto podría ocurrir en humanos. Nos encontramos ante hechos que, de probarse, tendrían una enorme trascendencia clínica.

          Translated abstract

          Summary Osteocalcin is a protein synthesized by the osteoblast. Before being released into the extracellular matrix, human osteocalcin undergoes gamma-carboxylation, as gamma-carboxy-glutamic acid binds at positions 17, 21 and 24. Part of the carboxylated and decarboxylated osteocalcin passes into the circulation. Since its discovery in the late 70s, it has been used as a marker of bone formation as it is an osteoblastic product and its role in the body is unknown. In recent years, osteocalcin has been identified as a hormone. Bone is considered an endocrine organ. Osteocalcin acting as a hormone is the decarboxylated form. Osteocalcin is involved in glucose homeostasis, skeletal muscle function, brain development, male fertility, hepatic steatosis, and arterial calcification. All of these facts have actually been tested in mice, but there is strong evidence that this could occur in humans. We are faced with facts that, if proven, would have enormous clinical significance.

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          Most cited references41

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          Integrative biology of exercise.

          Exercise represents a major challenge to whole-body homeostasis provoking widespread perturbations in numerous cells, tissues, and organs that are caused by or are a response to the increased metabolic activity of contracting skeletal muscles. To meet this challenge, multiple integrated and often redundant responses operate to blunt the homeostatic threats generated by exercise-induced increases in muscle energy and oxygen demand. The application of molecular techniques to exercise biology has provided greater understanding of the multiplicity and complexity of cellular networks involved in exercise responses, and recent discoveries offer perspectives on the mechanisms by which muscle "communicates" with other organs and mediates the beneficial effects of exercise on health and performance.
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            Exercise and the immune system: regulation, integration, and adaptation.

            Stress-induced immunological reactions to exercise have stimulated much research into stress immunology and neuroimmunology. It is suggested that exercise can be employed as a model of temporary immunosuppression that occurs after severe physical stress. The exercise-stress model can be easily manipulated experimentally and allows for the study of interactions between the nervous, the endocrine, and the immune systems. This review focuses on mechanisms underlying exercise-induced immune changes such as neuroendocrinological factors including catecholamines, growth hormone, cortisol, beta-endorphin, and sex steroids. The contribution of a metabolic link between skeletal muscles and the lymphoid system is also reviewed. The mechanisms of exercise-associated muscle damage and the initiation of the inflammatory cytokine cascade are discussed. Given that exercise modulates the immune system in healthy individuals, considerations of the clinical ramifications of exercise in the prevention of diseases for which the immune system has a role is of importance. Accordingly, drawing on the experimental, clinical, and epidemiological literature, we address the interactions between exercise and infectious diseases as well as exercise and neoplasia within the context of both aging and nutrition.
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              Endocrine regulation of energy metabolism by the skeleton.

              The regulation of bone remodeling by an adipocyte-derived hormone implies that bone may exert a feedback control of energy homeostasis. To test this hypothesis we looked for genes expressed in osteoblasts, encoding signaling molecules and affecting energy metabolism. We show here that mice lacking the protein tyrosine phosphatase OST-PTP are hypoglycemic and are protected from obesity and glucose intolerance because of an increase in beta-cell proliferation, insulin secretion, and insulin sensitivity. In contrast, mice lacking the osteoblast-secreted molecule osteocalcin display decreased beta-cell proliferation, glucose intolerance, and insulin resistance. Removing one Osteocalcin allele from OST-PTP-deficient mice corrects their metabolic phenotype. Ex vivo, osteocalcin can stimulate CyclinD1 and Insulin expression in beta-cells and Adiponectin, an insulin-sensitizing adipokine, in adipocytes; in vivo osteocalcin can improve glucose tolerance. By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism.
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                Author and article information

                Journal
                romm
                Revista de Osteoporosis y Metabolismo Mineral
                Rev Osteoporos Metab Miner
                Sociedad Española de Investigaciones Óseas y Metabolismo Mineral (Madrid, Madrid, Spain )
                1889-836X
                2173-2345
                December 2020
                : 12
                : 4
                : 146-151
                Affiliations
                [01] Móstoles Madrid orgnameHospital Universitario de Móstoles orgdiv1Cuidados Paliativos orgdiv2Equipo de Soporte Hospitalario España
                [02] Madrid orgnameFundación Jiménez Díaz orgdiv1Instituto de Investigación Sanitaria Fundación Jiménez Díaz orgdiv2Servicio de Traumatología y Cirugía Ortopédica España
                Article
                S1889-836X2020000400007 S1889-836X(20)01200400007
                10.4321/s1889-836x2020000400007
                c9494dc8-95ba-4a65-afb0-787853a8583c

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 09 January 2021
                : 30 November 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 41, Pages: 6
                Product

                SciELO Spain

                Categories
                Revisión

                glucose,esteatosis hepática,desarrollo cerebral,músculo esquelético,insulina,hormona,osteocalcina,arterial calcification,hepatic steatosis,glucosa,calcificación arterial,brain development,skeletal muscle,insulin,hormone,osteocalcin

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