title: Mechanical loading differentially regulates membrane-bound and soluble RANKL availability in MC3T3-E1 cells.
abstract: To understand the biochemical response of RANKL in response to mechanical loading, MC3T3-E1 cells were biequiaxially stretched. A murine RANKL cDNA with double epitopes, pEF6 HA-RANKL-V5His, was transfected into MC3T3-E1 cells, which were then stretched. Endogenous RANKL protein expression increased in response to mechanical loading. Membrane-bound RANKL (HA-RANKL-V5His) increased in cell lysates while soluble RANKL (RANKL-V5His) decreased in the conditioned media after mechanical loading. This may have resulted from the decreased activity of TACE after mechanical loading. Increased membrane-bound RANKL may be one of the mechanisms through which osteoblasts adapt to mechanical loading by regulating osteoclastogenic activity in a region-specific manner.
authors.affiliation: Center for Orthopaedic Research, Department of Orthopaedic Surgery Columbia University, 630 W. 168th Street, BB14-1411, New York, NY 10032, USA.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Hahn-Jun
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Karmin
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Seong-Sil
authors.initials: SS
authors.lastname: Chang
authors.forename: Ben
authors.initials: B
authors.lastname: Tolchin
authors.forename: Shiphin
authors.initials: S
authors.lastname: Lin
authors.forename: Sam K
authors.initials: SK
authors.lastname: Cho
authors.forename: Anthony
authors.initials: A
authors.lastname: Kwon
authors.forename: Jae Mok
authors.initials: JM
authors.lastname: Ahn
authors.forename: Francis Young-In
authors.initials: FY
authors.lastname: Lee
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001696:Biomechanical Phenomena; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D010805:Physical Conditioning, Animal; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D016474:Weight-Bearing
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse