title: Low-intensity pulsed ultrasound-promoted bone healing is not entirely cyclooxgenase 2 dependent.
abstract: OBJECTIVE
  The purpose of this study was to investigate whether low-intensity pulsed ultrasound (LIPUS) promotes bone healing through the cyclooxgenase 2 (COX-2) pathway.
  
  
  METHODS
  Each male Sprague Dawley rat (n = 48 total) in the study underwent bilateral drilled hole injury in the proximal tibiae. Then the animals were randomly assigned to 2 groups: a COX-2 inhibitor (COX-2in) group, treated with the selective COX-2 inhibitor rofecoxib (3 mg/kg/d), and a control (CON) group, treated with distilled water. Low-intensity pulsed ultrasound was applied to the injured site of a single limb of each rat for 20 min/d at a consistent intensity (30 mW/cm(2)) and frequency (1.5 MHz). Subsets of animals from both groups were killed after 3, 7, or 14 days of single-limb LIPUS treatment. Tissue sections were subjected to alcian blue staining, and the healing status was quantified according to a scoring system.
  
  
  RESULTS
  After 3 and 7 days, the CON group's LIPUS-treated limbs had significantly higher healing scores than its nontreated limbs and the COX-2in group's LIPUS-treated limbs (P < .05). Interestingly, after the 14-day treatment, the COX-2in group's LIPUS-treated limbs had significantly higher healing scores than its nontreated limbs (P < .05) but showed no difference when compared with the CON group.
  
  
  CONCLUSIONS
  Low-intensity pulsed ultrasound did show accelerative efficacy on bone healing. Selective inhibition of COX-2 could delay but not entirely block the benefits of LIPUS on bone healing. Low-intensity ultrasound treatment could promote bone healing through other, non-COX-2-dependent, pathways.
authors.affiliation: Institute of Physical Education, Health, and Leisure Studies, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Tsang-Hai
authors.initials: TH
authors.lastname: Huang
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
authors.forename: Hsiun-Ing
authors.initials: HI
authors.lastname: Chen
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Fu
authors.forename: Rong-Sen
authors.initials: RS
authors.lastname: Yang
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D017102:Fracture Healing / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D011829:Radiation Dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000528:radiation effects*; D013978:Tibial Fractures / Q000378:metabolism* / Q000628:therapy*; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat