Mechanical loading differentially regulates membrane-bound and soluble RANKL availability in MC3T3-E1 cells.
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.
Kim
Dae Won
DW
Center for Orthopaedic Research, Department of Orthopaedic Surgery Columbia University, 630 W. 168th Street, BB14-1411, New York, NY 10032, USA.
Lee
Hahn-Jun
HJ
Karmin
Jaime A
JA
Lee
Se Eun
SE
Chang
Seong-Sil
SS
Tolchin
Ben
B
Lin
Shiphin
S
Cho
Sam K
SK
Kwon
Anthony
A
Ahn
Jae Mok
JM
Lee
Francis Young-In
FY
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
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