Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism

Jin Zhang; Zhiwei Xu; Qisheng Tu; Jake Chen; Paloma Valverde; Xiaofang Zhu; Dana Murray; Yuwei Wu; Liming Yu; Hua Jiang; Michel M Dard; Jin Huang

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Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism

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Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domaincontaining 5(FNDC5) protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue(WAT) and uncoupling protein 1(UCP1) expression, leading to an increase in total body energy expenditure by augmented UCP1-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones,including growth plate, trabecular bone, cortical bone, articular cartilage, and bone–tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal(IP) administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-k B ligand(RANKL)-induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice.

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《骨研究（英文版）》 |2017年第1期|49-62|共14页
作者
Jin Zhang; Zhiwei Xu; Qisheng Tu; Jake Chen; Paloma Valverde; Xiaofang Zhu; Dana Murray; Yuwei Wu; Liming Yu; Hua Jiang; Michel M Dard; Jin Huang;
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Division of Oral Biology, Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA 02111, USA;

Department of Anatomy, Research Center for Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510405, China;

Department of Anatomy, Research Center for Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510405, China;

Division of Oral Biology, Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA 02111, USA;

Division of Oral Biology, Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA 02111, USA;

Department of Anatomy and Cel Biology, Tufts University School of Medicine and Sackler School of Graduate Biomedical Sciences, Boston, MA 02111, USA;

Department of Sciences, Center for Sciences and Biomedical Engineering, Boston, MA 02115, USA;

Division of Oral Biology, Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA 02111, USA;

Division of Oral Biology, Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA 02111, USA;

Division of Oral Biology, Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA 02111, USA;

Division of Oral Biology, Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA 02111, USA;

Division of Oral Biology, Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA 02111, USA;

Department of Periodontology and Implant Dentistry, New York University College of Dentistry, New York, NY 10010, USA;

Department of Anatomy, Research Center for Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510405, China;

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Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism

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