Reconciling the roles of FAK in osteoblast differentiation, osteoclast remodeling, and bone regeneration.
Integrins link the inside of a cell with its outside environment and in doing so regulate a wide variety of cell behaviors. Integrins are well known for their roles in angiogenesis and cell migration but their functions in bone formation are less clear. The majority of integrin signaling proceeds through focal adhesion kinase (FAK), an essential component of the focal adhesion complex. We generated transgenic mice in which FAK was deleted in osteoblasts and uncovered a previously unknown role in osteoblast differentiation associated with bone healing. FAK mutant cells migrated to the site of skeletal injury and angiogenesis was unaffected yet the transgenic mice still exhibited numerous defects in reparative bone formation. Osteoblast differentiation itself was unperturbed by the loss of FAK, whereas the attachment of osteoclasts to the bone matrix was disrupted in vivo. We postulate that defective bi-directional integrin signaling affects the organization of the collagen matrix. Finally, we present a compensatory candidate molecule, Pyk2, which localized to the focal adhesions in osteoblasts that were lacking FAK.
Kim
Jae-Beom
JB
Department of Stomatology, University of California at San Francisco, San Francisco, California, USA. jaebeom@gmail.com
Leucht
Philipp
P
Luppen
Cynthia A
CA
Park
Yu Jin
YJ
Beggs
Hilary E
HE
Damsky
Caroline H
CH
Helms
Jill A
JA
D000818:Animals; D001483:Base Sequence; D001857:Bone Matrix / Q000166:cytology; D001861:Bone Regeneration / Q000235:genetics / Q000502:physiology*; D016723:Bone Remodeling / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D047109:Fetal Development; D051417:Focal Adhesion Kinase 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051418:Focal Adhesion Kinase 2 / Q000502:physiology; D006579:Heterozygote; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology; D011247:Pregnancy; D015398:Signal Transduction
D017931:DNA Primers; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; C496051:Ptk2 protein, mouse; C496053:Ptk2b protein, mouse