FAK-Mediated mechanotransduction in skeletal regeneration.
The majority of cells are equipped to detect and decipher physical stimuli, and then react to these stimuli in a cell type-specific manner. Ultimately, these cellular behaviors are synchronized to produce a tissue response, but how this is achieved remains enigmatic. Here, we investigated the genetic basis for mechanotransduction using the bone marrow as a model system. We found that physical stimuli produced a pattern of principal strain that precisely corresponded to the site-specific expression of sox9 and runx2, two transcription factors required for the commitment of stem cells to a skeletogenic lineage, and the arrangement and orientation of newly deposited type I collagen fibrils. To gain insights into the genetic basis for skeletal mechanotransduction we conditionally inactivated focal adhesion kinase (FAK), an intracellular component of the integrin signaling pathway. By doing so we abolished the mechanically induced osteogenic response and thus identified a critical genetic component of the molecular machinery required for mechanotransduction. Our data provide a new framework in which to consider how physical forces and molecular signals are synchronized during the program of skeletal regeneration.
Leucht
Philipp
P
Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University, Stanford, California, United States of America.
Kim
Jae-Beom
JB
Currey
Jennifer A
JA
Brunski
John
J
Helms
Jill A
JA
D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D020342:Finite Element Analysis; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D007150:Immunohistochemistry; D040542:Mechanotransduction, Cellular; D051379:Mice; D012038:Regeneration
D051416:Focal Adhesion Protein-Tyrosine Kinases