RGD Reference Report - Lacunocanalicular fluid flow transduces mechanical tension stress during distraction osteogenesis. - Rat Genome Database

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Lacunocanalicular fluid flow transduces mechanical tension stress during distraction osteogenesis.

Authors: Davidson, EH  Sultan, SM  Butala, P  Knobel, D  Warren, SM 
Citation: Davidson EH, etal., J Craniofac Surg. 2013 Sep;24(5):1558-64. doi: 10.1097/SCS.0b013e31828f2060.
RGD ID: 10003162
Pubmed: PMID:24036726   (View Abstract at PubMed)
DOI: DOI:10.1097/SCS.0b013e31828f2060   (Journal Full-text)

The mechanotransduction mechanisms linking distraction device activation to new bone formation remain unknown. We hypothesize that the tension stress of activation during distraction osteogenesis is transmitted through lacunocanalicular fluid flow to initiate the osteogenic signaling cascade. Adult Sprague-Dawley rats (N = 24) were subjected to mandibular osteotomy and application of an external distraction device. After a 3-day latency period, half the animals (n = 12) underwent device activation at 0.25 mm twice daily for 6 days (total activation, 3 mm), and the other half (n = 12) had no activation. On day 10, the animals were injected with fluorescent reactive red lacunocanalicular tracer before killing. Mandibles were harvested, embedded, and sectioned, and reactive red epifluorescence lacunocanalicular flow was measured. Protein was harvested for focal adhesion kinase 1 (FAK1), NESPRIN1, SUN1, LAMIN A/C, and SMAD1 Western blotting as well as for bone morphogenetic protein (BMP)-2 enzyme-linked immunosorbent assay and alkaline phosphatase assay. Lacunocanalicular fluid flow was significantly greater in the distracted samples (60.5 +/- 14 vs 10.3 +/- 4 molecules of equivalent soluble fluorochrome per megapixel, P = 0.01). Flow distribution demonstrated the highest lacunocanalicular flow near the center of the distraction gap. Increased lacunocanalicular flow resulted in increased FAK1 (P = 0.009), NESPRIN1 (P = 0.01), SUN1 (P = 0.01), and LAMIN A/C (P = 0.008) expression. Focal adhesion kinase 1 activation in the presence of BMP-2 protein expression (P = 0.001) resulted in increased intranuclear SMAD1 phosphorylation (P = 0.04) and alkaline phosphatase activity (P < 0.0001). These findings suggest that activation of the distraction osteogenesis device affects cellular response through changes in lacunocanalicular fluid flow.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ossification  IEP 10003162 RGD 
response to mechanical stimulus  IEP 10003162; 10003162 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lmna  (lamin A/C)
Sun1  (Sad1 and UNC84 domain containing 1)


Additional Information