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H H Farman Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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K L Gustafsson Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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P Henning Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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L Grahnemo Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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V Lionikaite Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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S Movérare-Skrtic Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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J Wu Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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H Ryberg Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

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A Koskela Unit of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland

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J Tuukkanen Unit of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland

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E R Levin Division of Endocrinology, Departments of Medicine and Biochemistry, University of California, Irvine, California, USA
The Long Beach VA Medical Center, Long Beach, California, USA

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C Ohlsson Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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M K Lagerquist Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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-terminal type I collagen fragments were assessed using an ELISA RatLaps kit (CTX-I, Immunodiagnostic Systems) according to the manufacturer’s instructions. Serum levels of osteocalcin (OCN), a marker of bone formation, were determined with a mouse osteocalcin

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Sebastio Perrini Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari School of Medicine, Piazza Giulio Cesare, 11, I-70124 Bari, Italy

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Luigi Laviola Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari School of Medicine, Piazza Giulio Cesare, 11, I-70124 Bari, Italy

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Marcos C Carreira Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari School of Medicine, Piazza Giulio Cesare, 11, I-70124 Bari, Italy

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Angelo Cignarelli Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari School of Medicine, Piazza Giulio Cesare, 11, I-70124 Bari, Italy

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Annalisa Natalicchio Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari School of Medicine, Piazza Giulio Cesare, 11, I-70124 Bari, Italy

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Francesco Giorgino Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari School of Medicine, Piazza Giulio Cesare, 11, I-70124 Bari, Italy

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, which mediates most of the effects of GH on skeletal metabolism, promotes chondrogenesis and increases bone formation by regulating the functions of the differentiated osteoblasts ( Giustina et al . 2008 ). Figure 1 GH and IGF1 signaling and action in

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R Ørnsrud National Institute of Nutrition and Seafood Research, Department of Animal Physiology, School of Biological Sciences, PO Box 2029 Nordnes, N-5817 Bergen, Norway

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E J Lock National Institute of Nutrition and Seafood Research, Department of Animal Physiology, School of Biological Sciences, PO Box 2029 Nordnes, N-5817 Bergen, Norway
National Institute of Nutrition and Seafood Research, Department of Animal Physiology, School of Biological Sciences, PO Box 2029 Nordnes, N-5817 Bergen, Norway

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C N Glover National Institute of Nutrition and Seafood Research, Department of Animal Physiology, School of Biological Sciences, PO Box 2029 Nordnes, N-5817 Bergen, Norway

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G Flik National Institute of Nutrition and Seafood Research, Department of Animal Physiology, School of Biological Sciences, PO Box 2029 Nordnes, N-5817 Bergen, Norway

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key target for RA and CTR. In fish, CTR exerts effects directly on both osteoblasts and osteoclasts ( Wendelaar Bonga et al . 1983 ). Chronic CTR exposure increases bone formation, but may also impair mineralisation, at least in rats ( Wronski et al

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Rhonda D Prisby Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of
Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of
Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of
Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of

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Joshua M Swift Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of

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Susan A Bloomfield Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of
Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of

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Harry A Hogan Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of

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Michael D Delp Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of
Health and Kinesiology, Intercollegiate Faculty of Nutrition, Mechanical Engineering, INSERM U890, IFR 143, Université Jean-Monnet, Department of Applied Physiology and Kinesiology and the Center for Exercise Science, Departments of

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system. In fact, insulin stimulates osteoblastic activity ( Canalis et al . 1977 , Raisz & Kream 1983 ), resulting in enhanced bone formation. Consistent with this effect, BMDs in ZDF rats of the present study were greater in the distal femora ( Fig. 2

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Gerard Karsenty Department of Genetics and Development, Columbia University, HHSC 701 West 168th Street, HHSC1602, New York, New York 10032, USA

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sexual dimorphism in bone growth becomes apparent during puberty, at which time men reach higher peak bone mass ( Clarke & Khosla 2010 ). This skeletal sexual dimorphism is mainly due to a stimulatory androgen action on periosteal bone formation in men

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Soo Yeon Jang Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea

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Kyung Mook Choi Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea

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support its role in clinical practice is still weak. Effects of RANKL–RANK on osteoblast RANKL is important not only for bone resorption but also for bone formation. Ikebuchi et al. proposed the concept of RANKL reverse signaling ( Ikebuchi et

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E Mrak Bone Metabolic Unit,
Endocrine Unit, Scientific Institute San Raffaele, Via Olgettina, 60, 20132 Milano, Italy
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy

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I Villa Bone Metabolic Unit,
Endocrine Unit, Scientific Institute San Raffaele, Via Olgettina, 60, 20132 Milano, Italy
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy

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R Lanzi Bone Metabolic Unit,
Endocrine Unit, Scientific Institute San Raffaele, Via Olgettina, 60, 20132 Milano, Italy
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy

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M Losa Bone Metabolic Unit,
Endocrine Unit, Scientific Institute San Raffaele, Via Olgettina, 60, 20132 Milano, Italy
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy

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F Guidobono Bone Metabolic Unit,
Endocrine Unit, Scientific Institute San Raffaele, Via Olgettina, 60, 20132 Milano, Italy
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy

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A Rubinacci Bone Metabolic Unit,
Endocrine Unit, Scientific Institute San Raffaele, Via Olgettina, 60, 20132 Milano, Italy
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy

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patients, who have chronic systemic GH and IGF-I excess, are characterized by increased bone turnover and biochemical markers of bone formation and bone resorption that correlate with circulating GH and IGF-I levels, suggesting the activation of both

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Anurag Bajpai Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia
Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia

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Peter J Simm Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia
Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia
Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia

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Stephen J McPherson Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia

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Vincenzo C Russo Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia
Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia
Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia

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Walid J Azar Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia
Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia
Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia

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John D Wark Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia

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Gail P Risbridger Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia

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George A Werther Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia
Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia
Department of Endocrinology and Diabetes, Murdoch Childrens Research Institute, Department of Paediatrics, Prostate and Breast Cancer Research Group, Department of Medicine and Bone and Mineral Service, Royal Children's Hospital, Parkville, Melbourne, Victoria 3052, Australia

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separated and stored at −70 °C until analysis. The animals were culled by injecting pentobarbital (0.5 ml of 340 mg/ml; Virbac Animal Health, NSW, Australia). Figure 1 Results from bone turnover markers. (a) No significant difference in bone formation, as

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S F Ahmed
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C Farquharson Developmental Endocrinology Research Group, Bone Biology Group, Division of Developmental Medicine, Department of Child Health, Royal Hospital For Sick Children, University of Glasgow, Yorkhill, Glasgow G3 8SJ, UK

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et al . 2006 ). This effect, associated with modest mitogenic properties, causes an increase in the number of osteoblasts, and an increase in osteoblastic function and bone formation ( Canalis 1980 ). The effect of IGF1 on bone resorption is less

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Masaki Nakano Department of Biology, College of Liberal Arts and Sciences, Tokyo Medical and Dental University, Chiba, Japan
Department of Biology, Faculty of Science, Toho University, Chiba, Japan

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Mika Ikegame Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

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Junko Igarashi-Migitaka Department of Anatomy and Cell Biology, St. Marianna University School of Medicine, Kawasaki, Japan

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Yusuke Maruyama Department of Biology, College of Liberal Arts and Sciences, Tokyo Medical and Dental University, Chiba, Japan

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Nobuo Suzuki Noto Marine Laboratory, Institute of Nature and Environmental Technology, Kanazawa University, Ishikawa, Japan

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Atsuhiko Hattori Department of Biology, College of Liberal Arts and Sciences, Tokyo Medical and Dental University, Chiba, Japan

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influenced by ambient light conditions, is better suited to evaluate the in vivo effect of exogenous melatonin administration on bone formation. The use of chick calvariae as a model of bone demonstrated the expression of the melatonin receptors and

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