Pulsed electromagnetic fields stimulate osteogenic differentiation and maturation of osteoblasts by upregulating the expression of BMPRII localized at the base of primary cilium.

Author: Xie YF1, Shi WG2, Zhou J3, Gao YH4, Li SF5, Fang QQ6, Wang MG7, Ma HP8, Wang JF9, Xian CJ10, Chen KM11
Affiliation: <sup>1</sup>Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: xieyanfang@lut.cn. <sup>2</sup>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. <sup>3</sup>Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: zhouj12@lzu.edu.cn. <sup>4</sup>Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: guyansuo@gsau.edu.cn. <sup>5</sup>Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: leesf@st.gsau.edu.cn. <sup>6</sup>Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: 132085238002@lut.cn. <sup>7</sup>School of life science and engineering, Lanzhou University of Technology, Lanzhou 730050, People's Republic of China. Electronic address: mgwang@lut.cn. <sup>8</sup>Department of Pharmacy, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: mahuiping2014@gszy.edu.cn. <sup>9</sup>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. <sup>10</sup>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. <sup>11</sup>Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China. Electronic address: chenkm@lut.cn.
Conference/Journal: Bone.
Date published: 2016 Dec
Other: Volume ID: 93 , Pages: 22-32 , Special Notes: doi: 10.1016/j.bone.2016.09.008. Epub 2016 Sep 10. , Word Count: 234


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.

Copyright © 2016 Elsevier Inc. All rights reserved.

KEYWORDS: BMP-Smad1/5/8 signaling; BMPRII; Osteoblasts; Primary cilia; Pulsed electromagnetic fields

PMID: 27622883 DOI: 10.1016/j.bone.2016.09.008