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      Bone-Derived Extracellular Vesicles: Novel Players of Interorgan Crosstalk

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          Abstract

          An increasing number of studies have shown that bone plays an active role in regulating glucose metabolism, affects renal, and cardiovascular diseases and even influences the development of offspring. These novel findings have indicated that bone plays a much more important role in the human body than only providing physical support. However, further investigations of the mechanisms underlying the effects of bone are needed. Recently, extracellular vesicles (EVs) have received increased attention because they can transfer functional proteins, mRNAs, and miRNAs between cells/organs. After reviewing the existing evidence, we hypothesized that bone may be involved in interorgan communication via EVs. Further research exploring bone-derived EVs may facilitate the understanding of bone as a multifunctional organ.

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          Most cited references45

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          Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation

          Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation.
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            Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise

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              Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism.

              The metabolically active and perpetually remodeling calcium phosphate-based endoskeleton in terrestrial vertebrates sets the demands on whole-organism calcium and phosphate homeostasis that involves multiple organs in terms of mineral flux and endocrine cross talk. The fibroblast growth factor (FGF)-Klotho endocrine networks epitomize the complexity of systems biology, and specifically, the FGF23-αKlotho axis highlights the concept of the skeleton holding the master switch of homeostasis rather than a passive target organ as hitherto conceived. Other than serving as a coreceptor for FGF23, αKlotho circulates as an endocrine substance with a multitude of effects. This review covers recent data on the physiological regulation and function of the complex FGF23-αKlotho network. Chronic kidney disease is a common pathophysiological state in which FGF23-αKlotho, a multiorgan endocrine network, is deranged in a self-amplifying vortex resulting in organ dysfunction of the utmost severity that contributes to its morbidity and mortality.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                10 December 2019
                2019
                : 10
                : 846
                Affiliations
                Department of Orthopedics, General Hospital of Chinese PLA , Beijing, China
                Author notes

                Edited by: Andrea Del Fattore, Bambino Gesù Children Hospital (IRCCS), Italy

                Reviewed by: Michela Rossi, Bambino Gesù Children Hospital (IRCCS), Italy; David M. Findlay, University of Adelaide, Australia

                *Correspondence: Peifu Tang pftang301@ 123456163.com

                This article was submitted to Bone Research, a section of the journal Frontiers in Endocrinology

                †These authors have contributed equally to this work

                Article
                10.3389/fendo.2019.00846
                6914759
                de59b5e2-a709-4c9d-a3a2-4fbd3b09c88b
                Copyright © 2019 Li, Yin, Guo, Lv, Deng, Chen, Gu, Tang and Zhang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 July 2019
                : 20 November 2019
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 61, Pages: 6, Words: 4806
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81702176
                Award ID: 81772369
                Categories
                Endocrinology
                Hypothesis and Theory

                Endocrinology & Diabetes
                extracellular vesicles,interorgan crosstalk,bone factors,osteocalcin,fgf23 = fibroblast growth factor 23,exosomes

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