title: Single-pulsed electromagnetic field therapy increases osteogenic differentiation through Wnt signaling pathway and sclerostin downregulation.
abstract: Pulsed electromagnetic field (PEMF) therapy has been used for more than three decades to treat bone diseases. The main complaint about using PEMF is that it is time-consuming. Previously, we showed single-pulsed electromagnetic field (SPEMF) applied for 3 min daily increased osteogenic differentiation of mesenchymal stem cells and accelerated bone growth in a long bone defect model. In the current study, we investigated the mechanism of SPEMF to increase osteogenic differentiation in osteoblastic cells. We found that both short-term (SS) and long-term (SL) SPEMF treatment increased mineralization, while alkaline phosphatase (ALP) activity increased during the first 5 days of SPEMF treatment. SS treatment increased gene expression of Wnt1, Wnt3a, Wnt10b, Fzd9, ALP, and Bmp2. Also, SPEMF inhibited sclerostin after 5 days of treatment, and that inhibition was more significant with SL treatment. SL SPEMF increased expression of parathyroid hormone-related protein (PTHrP) but decreased expression of Sost gene, which encodes sclerostin. Together, the early osteogenic effect of SPEMF utilizes the canonical Wnt signaling pathway while the inhibitory effect of long-term SPEMF on sclerostin may be attributable to PTHrP upregulation. This study enhances our understanding of cellular mechanisms to support the previous finding and may provide new insight for clinical applications.
authors.affiliation: Bone and Joint Research Center, National Cheng Kung University, Tainan, Taiwan.|Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Chun
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Bone and Joint Research Center, National Cheng Kung University, Tainan, Taiwan.|College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ru-Wei
authors.initials: RW
authors.lastname: Lin
authors.affiliation: Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Bone and Joint Research Center, National Cheng Kung University, Tainan, Taiwan.|Department of Orthopedic Surgery, University of Virginia, Charlottesville, Virginia.|Graduate Institute of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Gwo-Jaw
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: Bone and Joint Research Center, National Cheng Kung University, Tainan, Taiwan.|Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kuo-An
authors.initials: KA
authors.lastname: Lai
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002113:Calcification, Physiologic / Q000502:physiology; D015536:Down-Regulation; D004574:Electromagnetic Fields; D006023:Glycoproteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D055909:Magnetic Field Therapy / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D044162:Parathyroid Hormone-Related Protein; C486030:Sost protein, mouse; D000469:Alkaline Phosphatase
keywords: BMPs (bone morphogenetic proteins); PTHrP (parathyroid hormone-related protein); SPEMF; Wnt pathway; sclerostin