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The interdependent relationship between the nitric oxide signaling pathway and primary cilia in pulse electromagnetic field-stimulated osteoblastic differentiation

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dc.contributor.authorHe, W.F.
dc.contributor.authorQin, R.
dc.contributor.authorGao, Y.H.
dc.contributor.authorZhou, J.
dc.contributor.authorWei, J.J.
dc.contributor.authorLiu, J.
dc.contributor.authorHou, X.F.
dc.contributor.authorMa, H.P.
dc.contributor.authorXian, C.J.
dc.contributor.authorLi, X.Y.
dc.contributor.authorChen, K.M.
dc.date.issued2022
dc.description.abstractPulsed electromagnetic fields (PEMFs) have long been recognized being safe and effective in treating bone fracture nonunion and osteoporosis. However, the mechanism of osteogenic action of PEMFs is still unclear. While primary cilia are reported to be a sensory organelle for PEMFs, and nitric oxide (NO) plays an indispensable role in osteogenic effect of PEMFs, the relationship between NO and primary cilia is unknown. In this study, effects of treatment with 50 Hz 0.6 mT PEMFs on osteogenic differentiation and mineralization, NO secretion, and ciliary location of specific proteins were examined in rat calvarial osteoblasts (ROBs) with normal or abrogated primary cilia. It was found that PEMFs stimulated the osteogenic differentiation by activating the NOS/NO/sGC/cGMP/PKG signaling pathway, which need the existence of primary cilia. All components of the signaling pathway including iNOS, eNOS, sGC, PKG-1, and PKG-2 were localized to primary cilia, and eNOS was phosphorylated inside the primary cilia. Besides, primary cilia were elongated significantly by PEMF treatment and changed dynamically with the activation NO/cGMP pathway. When the pathway was blocked by L-NAME, PEMFs could no longer elongate the primary cilia and stimulate the osteoblastic differentiation. Thus, this study for the first time observed activation of the NO/cGMP signaling pathway in ciliary compartment of osteoblasts, and PEMFs could not stimulate the osteoblastic differentiation if the NO signaling pathway was blocked or the ciliogenesis was inhibited. Our findings indicate the interdependent relationship between NO and primary cilia in the PEMF-promoted osteogenesis.
dc.identifier.citationThe FASEB Journal, 2022; 36(6)
dc.identifier.doi10.1096/fj.202101577RR
dc.identifier.issn0892-6638
dc.identifier.issn1530-6860
dc.identifier.orcidXian, C.J. [0000-0002-8467-2845]
dc.identifier.urihttps://hdl.handle.net/11541.2/31527
dc.language.isoen
dc.publisherWILEY
dc.relation.fundingNSFC 81770879
dc.relation.fundingYouth Project of Gansu Science Foundation 20JR5RA589
dc.rightsCopyright 2022 Federation of American Societies for Experimental Biology. Access Condition Notes: Accepted manuscript is available open access
dc.source.urihttps://doi.org/10.1096/fj.202101577rr
dc.subjectCilia
dc.subjectOsteoblasts
dc.subjectAnimals
dc.subjectRats
dc.subjectNitric Oxide
dc.subjectCyclic GMP
dc.subjectSignal Transduction
dc.subjectCell Differentiation
dc.subjectOsteogenesis
dc.subjectElectromagnetic Fields
dc.titleThe interdependent relationship between the nitric oxide signaling pathway and primary cilia in pulse electromagnetic field-stimulated osteoblastic differentiation
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12252245370001831 13305829950001831 9916646493301831_OAP
ror.mmsid9916646493301831

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