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K L Gustafsson Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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K H Nilsson Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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H H Farman Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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A Andersson Center for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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V Lionikaite Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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P Henning Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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J Wu Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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S H Windahl Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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U Islander Center for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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S Movérare-Skrtic Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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K Sjögren Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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H Carlsten Center for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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J-Å Gustafsson Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA

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C Ohlsson Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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M K Lagerquist Center for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Introduction Estrogen, the main female reproductive hormone, is a major regulator of bone homeostasis and it is well known that estrogen deficiency after menopause increases fracture risk and that estrogen treatment decreases this risk

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Shan-Jin Wang Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China

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Xin-Feng Li Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China

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Lei-Sheng Jiang Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China

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Li-Yang Dai Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China

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several growth factors and hormones. One of the key regulators of endochondral bone development is estrogen ( Perry et al . 2008 ). Estrogen exerts its effect via traditional genomic interactions with two nuclear receptors, namely estrogen receptor α (ERα

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Lingyun Lu Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China

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Li Tian Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China

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significant feature of aging in women. Menopause leads to a change in the concentration of hormones, especially that of estrogen ( Fuentes & Silveyra 2019 , Geraci et al. 2021 ). In addition, the occurrence of osteoporosis and sarcopenia is closely related

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Liyuan Tian Molecular Biology, Endocrinology, Departments of

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Zhiqiang Wu Molecular Biology, Endocrinology, Departments of

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Yali Zhao Molecular Biology, Endocrinology, Departments of

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Yuanguang Meng Molecular Biology, Endocrinology, Departments of

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Yiling Si Molecular Biology, Endocrinology, Departments of

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Xiaobing Fu Molecular Biology, Endocrinology, Departments of

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Yiming Mu Molecular Biology, Endocrinology, Departments of

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Weidong Han Molecular Biology, Endocrinology, Departments of

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Introduction Estrogen plays a crucial role in the control of development, sexual behavior, and reproductive functions. Its effects have been linked to the onset and progression of gynecological malignancies including breast cancer and endometrial

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Tony K S Ku University of Illinois Cancer Center, Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 801 South Paulina Street, Chicago, Illinois 60612, USA

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David L Crowe University of Illinois Cancer Center, Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 801 South Paulina Street, Chicago, Illinois 60612, USA

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( Couse & Korach 1999 ). ERs belong to the superfamily of nuclear hormone receptors that are ligand-dependent transcription factors ( Mangelsdorf et al. 1995 ). The ERα binds to estrogen response elements in the promoters of responsive genes. A number of

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Malin Hedengran Faulds
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Chunyan Zhao
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Karin Dahlman-Wright
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Jan-Åke Gustafsson Department of Biosciences and Nutrition, Center for Nuclear Receptors and Cell Signaling, Novum, Karolinska Institutet, S-141 83 Huddinge, Sweden

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Estrogen signaling Estrogens exert their physiological effects through two estrogen receptor (ER) subtypes, ERα and ERβ that belong to the nuclear receptor family of ligand-activated transcription factors. ERα is mainly expressed in reproductive

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Graham W Aberdeen Departments of Obstetrics, Gynecology, Reproductive Sciences and Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA

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Jeffery S Babischkin Departments of Obstetrics, Gynecology, Reproductive Sciences and Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA

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Gerald J Pepe Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia, USA

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Eugene D Albrecht Departments of Obstetrics, Gynecology, Reproductive Sciences and Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA

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levels or action of estrogen are curtailed or reduced during human pregnancy, e.g. preterm birth, aromatase gene mutation, or endocrine disruptors that interfere with estrogen receptor action, lead to T2DM in offspring ( Hofman et al. 2004

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Sivaporn Sivasinprasasn School of Medicine, Mae Fah Luang University, Chiang Rai, Thailand
Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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Siripong Palee Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand

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Kenneth Chattipakorn Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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Thidarat Jaiwongkum Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand

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Nattayaporn Apaijai Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand

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Wasana Pratchayasakul Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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Siriporn C Chattipakorn Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand

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Nipon Chattipakorn Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

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estrogen deprivation by bilateral ovariectomy (OVX) caused an increase in mortality from CVD, while estrogen could reduce the risk, indicating its beneficial effects on the heart ( Rivera et al. 2009 ). Also, endogenous estrogen deficiency resulted in

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Tian Shuang Cardiovascular and Metabolic Research Unit, Laurentian University, Ontario, Canada
School of Human Kinetics, Faculty of Health, Laurentian University, Ontario, Canada
Department of Biology, Laurentian University, Ontario, Canada

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Ming Fu Cardiovascular and Metabolic Research Unit, Laurentian University, Ontario, Canada
School of Human Kinetics, Faculty of Health, Laurentian University, Ontario, Canada
Health Sciences North Research Institute, Sudbury, Ontario, Canada

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Guangdong Yang Cardiovascular and Metabolic Research Unit, Laurentian University, Ontario, Canada
Department of Chemistry and Biochemistry, Laurentian University, Ontario, Canada

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Ying Huang Cardiovascular and Metabolic Research Unit, Laurentian University, Ontario, Canada
School of Human Kinetics, Faculty of Health, Laurentian University, Ontario, Canada

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Zhongming Qian Nantong University, Nantong, Jiangsu, China

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Lingyun Wu Cardiovascular and Metabolic Research Unit, Laurentian University, Ontario, Canada
School of Human Kinetics, Faculty of Health, Laurentian University, Ontario, Canada
Health Sciences North Research Institute, Sudbury, Ontario, Canada

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Rui Wang Cardiovascular and Metabolic Research Unit, Laurentian University, Ontario, Canada
Department of Biology, Laurentian University, Ontario, Canada
Department of Biology, York University, Toronto, Ontario, Canada

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Introduction Cardiovascular beneficiary effects of estrogen have been widely reported in human studies, such as the reduced incidence of cardiovascular diseases in premenopausal women ( Reslan & Khalil 2012 , Yang et al. 2013 ). Studies

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Shisan Xu Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Fangjing Xie Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Li Tian Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Samane Fallah Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Fatemeh Babaei Department of Chemistry, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Sinai H C Manno Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Francis A M Manno III School of Biomedical Engineering, Faculty of Engineering, University of Sydney, Sydney, New South Wales, Australia

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Lina Zhu Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Kin Fung Wong Department of Biomedical Engineering, Polytechnic University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Yimin Liang Department of Chemistry, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Rajkumar Ramalingam Department of Chemistry, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Lei Sun Department of Biomedical Engineering, Polytechnic University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Xin Wang Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Robert Plumb Waters Technologies Corporation, Milford, Massachusetts, USA

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Lee Gethings Waters Technologies Corporation, Milford, Massachusetts, USA

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Yun Wah Lam Department of Chemistry, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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Shuk Han Cheng Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong SAR, People’s Republic of China
State Key Laboratory of Marine Pollution (SKLMP) at City University of Hong Kong, Hong Kong SAR, People’s Republic of China
Department of Materials Science and Engineering, College of Science and Engineering, City University of Hong Kong, Hong Kong SAR, People’s Republic of China

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cardiomyocytes are sexually dimorphic ( Isensee et al . 2008 , Tsuji et al . 2017 ), and estrogen receptor expression is deregulated in some cardiomyopathies ( Mahmoodzadeh et al . 2006 ). Despite the apparent involvement of estrogen in CVD, clinical

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