Pulsed electromagnetic fields stimulate osteogenic differentiation and maturation of osteoblasts by upregulating the expression of BMPRII localized at the base of primary cilium |
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| Institution: | 1. Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People''s Republic of China;2. Gansu Key laboratory of Space Radiobiology, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, People''s Republic of China;3. School of life science and engineering, Lanzhou University of Technology, Lanzhou 730050, People''s Republic of China;4. Department of Pharmacy, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People''s Republic of China;5. Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia;1. University of Michigan Department of Orthopaedic Surgery, Ann Arbor, MI, United States;2. University of Michigan Department of Biomedical Engineering, Ann Arbor, MI, United States;3. Bone and Extracellular Matrix Branch, National Institute of Child Health and Human Disorders, NIH, Bethesda, MD, United States;1. Cranfield Forensic Institute, Cranfield University, Defence Academy of the UK, Shrivenham, UK;2. Forensic Odontology, Melbourne Dental School, University of Melbourne, Melbourne, Australia;3. The Imaging Science Group, Nottingham Trent University, Nottingham, UK;4. Cobalt Health, Cheltenham, UK;5. Social and Community Medicine, Bristol University, Bristol, UK;6. Physics and Astronomy, Exeter University, Exeter, UK;1. Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China;2. State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China;3. Key Laboratory of Chinese Academy of Sciences for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China;1. Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States;2. Centre for Bone and Arthritis Research at Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden;3. Department of Molecular Periodontology, Umeå University, Umeå, Sweden;4. Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm, Germany |
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| Abstract: | Pulsed electromagnetic fields (PEMFs) have been considered as a potential candidate for the prevention and treatment of osteoporosis, however, the mechanism of its action is still elusive. We have previously reported that 50 Hz 0.6 mT PEMFs stimulate osteoblastic differentiation and mineralization in a primary cilium- dependent manner, but did not know the reason. In the current study, we found that the PEMFs promoted osteogenic differentiation and maturation of rat calvarial osteoblasts (ROBs) by activating bone morphogenetic protein BMP-Smad1/5/8 signaling on the condition that primary cilia were normal. Further studies revealed that BMPRII, the primary binding receptor of BMP ligand, was readily and strongly upregulated by PEMF treatment and localized at the bases of primary cilia. Abrogation of primary cilia with small interfering RNA sequence targeting IFT88 abolished the PEMF-induced upregulation of BMPRII and its ciliary localization. Knockdown of BMPRII expression level with RNA interference had no effects on primary cilia but significantly decreased the promoting effect of PEMFs on osteoblastic differentiation and maturation. These results indicated that PEMFs stimulate osteogenic differentiation and maturation of osteoblast by primary cilium-mediated upregulation of BMPRII expression and subsequently activation of BMP-Smad1/5/8 signaling, and that BMPRII is the key component linking primary cilium and BMP-Smad1/5/8 pathway. This study has thus revealed the molecular mechanism for the osteogenic effect of PEMFs. |
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