Pulsed electromagnetic fields stimulate osteogenic differentiation and maturation of osteoblasts by upregulating the expression of BMPRII localized at the base of primary cilium.
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 50Hz 0.6mT 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.
Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: xieyanfang@lut.cn.
Yan-Fang
YF
Xie
Gansu Key laboratory of Space Radiobiology, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, People's Republic of China. Electronic address: shiwengui@impcas.ac.cn.
Wen-Gui
WG
Shi
Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: zhouj12@lzu.edu.cn.
Jian
J
Zhou
Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: guyansuo@gsau.edu.cn.
Yu-Hai
YH
Gao
Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: leesf@st.gsau.edu.cn.
Shao-Feng
SF
Li
Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: 132085238002@lut.cn.
Qing-Qing
QQ
Fang
School of life science and engineering, Lanzhou University of Technology, Lanzhou 730050, People's Republic of China. Electronic address: mgwang@lut.cn.
Ming-Gang
MG
Wang
Department of Pharmacy, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: mahuiping2014@gszy.edu.cn.
Hui-Ping
HP
Ma
Gansu Key laboratory of Space Radiobiology, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, People's Republic of China. Electronic address: jufangwang@impcas.ac.cn.
Ju-Fang
JF
Wang
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia. Electronic address: cory.xian@unisa.edu.au.
Cory J
CJ
Xian
Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: chenkm@lut.cn.
Ke-Ming
KM
Chen
D000818:Animals; D000831:Animals, Newborn; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002923:Cilia / Q000378:metabolism*; D004574:Electromagnetic Fields; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D002352:Carrier Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D034741:RNA, Small Interfering; D051785:Smad Proteins; D025521:Tumor Suppressor Proteins; D000099176:Noggin Protein; C554430:LDN 193189
BMP-Smad1/5/8 signaling; BMPRII; Osteoblasts; Primary cilia; Pulsed electromagnetic fields