Prolonged endochondral bone healing in senescence is shortened by low-intensity pulsed ultrasound in a manner dependent on COX-2.
To test whether mechanical loading produces faster healing in aged mice, fractured femurs of aged 1-year-old mice were subjected to low-intensity pulsed ultrasound (LIPUS), a treatment that is routinely used to help heal fractures in humans. Cyclooxygenase-2 knockout mice (COX-2(-/-)), which lack an immediate early mediator of mechanical stimulation, were also studied by histochemistry, microcomputed tomography and quantitative polymerase chain reaction to determine the role of COX-2. The healing in the aged COX-2(-/-) mice is slow during the endochondral bone remodeling (>30 d), a period generally prolonged in senescence. For aged wild-type mice, LIPUS halved the endochondral phase to about 10 d, whereas that was not the case for aged COX-2(-/-) mice, which showed no apparent shortening of the prolonged endochondral-phase healing time. Injecting prostaglandin E(2) receptor agonists, however, rescued the COX-2(-/-) callus from insensitivity to LIPUS. In conclusion, COX-2 is a limiting factor in the delayed endochondral bone healing and is induced by LIPUS, which normalizes healing rate to the wild-type level.
Naruse
Kouji
K
Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
Sekiya
Hideki
H
Harada
Yoshihumi
Y
Iwabuchi
Sadahiro
S
Kozai
Yusuke
Y
Kawamata
Ryota
R
Kashima
Isamu
I
Uchida
Kentaro
K
Urabe
Ken
K
Seto
Kannichi
K
Itoman
Moritoshi
M
Mikuni-Takagaki
Yuko
Y
D000375:Aging / Q000528:radiation effects; D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D005264:Femoral Fractures / Q000503:physiopathology* / Q000628:therapy*; D005269:Femur / Q000503:physiopathology* / Q000528:radiation effects*; D017102:Fracture Healing / Q000528:radiation effects*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011829:Radiation Dosage; D015398:Signal Transduction / Q000528:radiation effects; D014464:Ultrasonic Therapy / Q000379:methods*
D008565:Membrane Proteins; D051545:Cyclooxygenase 1; C496512:Ptgs1 protein, mouse