Mechanical strain inhibits expression of osteoclast differentiation factor by murine stromal cells.
Normal dynamic loading prevents bone resorption; however, the means whereby biophysical factors reduce osteoclast activity are not understood. We show here that mechanical strain (2% at 10 cycles per minute) applied to murine marrow cultures reduced 1, 25(OH)(2)D(3)-stimulated osteoclast formation by 50%. This was preceded by decreased expression of osteoclast differentiation factor (ODF/TRANCE). RT-PCR for ODF/TRANCE revealed that ODF/TRANCE mRNA in strained cultures was 59 +/- 3% of that seen in control cultures. No significant effects on total cell count, thymidine uptake, or alkaline phosphatase activity were induced by strain. To isolate the cell targeted by strain, primary stromal cells were cultured from marrow. Mechanical strain also reduced mRNA for ODF/TRANCE to 60% that of control in these cells. In contrast, mRNA for membrane-bound macrophage colony-stimulating factor was not significantly affected. Soluble ODF ( approximately 2 ng/ml) was able to reverse the effect of strain, returning osteoclast numbers to control. Because osteoclast formation is dependent upon ODF/TRANCE expression, strain-induced reductions in this factor may contribute to the accompanying reduction in osteoclastogenesis.
Rubin
J
J
Department of Medicine, Veterans Affairs Medical Center and Emory University, Atlanta, GA 30033, USA. jrubi02@emory.edu
Murphy
T
T
Nanes
M S
MS
Fan
X
X
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor; D000469:Alkaline Phosphatase; D002117:Calcitriol