Focal adhesion kinase expression during mandibular distraction osteogenesis: evidence for mechanotransduction.
Distraction osteogenesis is an established treatment strategy in the reconstruction of the craniofacial skeleton. The underlying mechanisms that drive bone formation during this process are largely unknown, but a regulatory role for mechanical force is believed to be critical. The integrin-mediated signal transduction cascade is a primary pathway by which signal transduction of mechanical stimuli (i.e., mechanotransduction) occurs. Focal adhesion kinase (FAK) is a significant regulator in this pathway. The authors hypothesize that mechanical forces created during distraction osteogenesis are responsible for the osteogenic response that takes place, and that these changes arise through integrin-dependent mechanotransduction. Using a rat model of distraction osteogenesis, the authors examined the expression of FAK in critical size defects (n = 15), subcritical size defects (n = 15), and mandibles undergoing distraction osteogenesis (n = 15). Their findings demonstrated FAK immunolocalization in mandibles undergoing distraction osteogenesis, but not in the critical size defects or in subcritical size defects, despite varying degrees of bone formation in the latter two groups. Furthermore, bone sialoprotein mRNA in situ hybridization patterns were found to mirror FAK immunolocalization patterns in mandibles undergoing distraction osteogenesis, demonstrating an association of FAK expression with the osteogenic process specific to distraction osteogenesis. These findings suggest that the bone formation in distraction osteogenesis is regulated by mechanical force by means of integrin-dependent mechanotransduction pathways.
Tong
Lawrence
L
Section of Plastic and Reconstructive Surgery and Section of Orthopedic Surgery, Department of Surgery, University of Michigan, Ann Arbor 48109, USA.
Buchman
Steven R
SR
Ignelzi
Michael A
MA
Rhee
Samuel
S
Goldstein
Steven A
SA
D000818:Animals; D001861:Bone Regeneration / Q000502:physiology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions; D007150:Immunohistochemistry; D016023:Integrins / Q000502:physiology; D008334:Mandible / Q000201:enzymology* / Q000502:physiology / Q000601:surgery; D040542:Mechanotransduction, Cellular; D019857:Osteogenesis, Distraction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016023:Integrins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat