Absence of beta3 integrin accelerates early skeletal repair.
Integrins are heterodimeric transmembrane proteins that mediate cell-matrix interactions and modulate cell behavior. Beta3 subunit is a component of alphaIIbeta3 and alphaVbeta3 integrins. In this study, we first determined that beta3 transcripts are expressed by cells within fracture calluses at 7 and 10 days after injury in a mouse model. We then analyzed fracture healing in mice deficient of beta3 integrin with molecular, histomorphometric, and biomechanical techniques. We found that lack of beta3 integrin results in an extended bleeding time and leads to more bone formation and accelerated cartilage maturation at 7 days after injury. However, beta3 deficiency does not appear to affect later fracture healing. At days 14 and 21, histological appearance or biomechanical properties of fracture calluses are similar between wild type and mutant mice. We also found that altered fracture healing in beta3-null mice is not associated with accelerated angiogenesis, because no significant difference of length density and surface density of blood vessels in fracture limbs was detected at 3 days after injury between wild type and beta3-null mice. In conclusion, our findings demonstrate that beta3 integrin plays an important role during early fracture healing. Further research is required to determine the underlying mechanisms.
Hu
Diane
D
Orthopaedic Trauma Institute, San Francisco General Hospital, University of California at San Francisco, 1001 Potrero Avenue, San Francisco, California 94110, USA.
Lu
Chuanyong
C
Sapozhnikova
Anna
A
Barnett
Michael
M
Sparrey
Carolyn
C
Miclau
Theodore
T
Marcucio
Ralph S
RS
D000818:Animals; D001696:Biomechanical Phenomena; D002146:Bony Callus / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism; D004195:Disease Models, Animal; D017102:Fracture Healing / Q000502:physiology*; D039661:Integrin beta3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013977:Tibia / Q000293:injuries / Q000378:metabolism; D013978:Tibial Fractures / Q000378:metabolism*
D039661:Integrin beta3