title: 13. Effect of Low-Intensity Pulsed Ultrasound (LIPUS) on Remote Bone Marrow in Rats With Healing Socket.
abstract: OBJECTIVE
  We reported at the previous annual meeting that LIPUS treatment of the molar tooth sockets of retired breeder rats accelerated alveolar bone healing, and that associated humoral effects were seen with elevated blood flow. Namely, LIPUS induced VEGF/angiogenesis along with elevated baseline blood flow rate, which was further associated with a sudden depression of blood flow rate in the socket immediately after cessation of LIPUS treatment. Prior injection with EP4 PGE2 receptor antagonist, but not EP3 antagonist, abolished this LIPUS-induced depression, and topical application of PGE2 to the socket epithelium mimicked the LIPUS-induced depression. In fact, the serum level of PGE2 increased after LIPUS treatment, and significantly increased in the blood flow rate at remote sites on the foot dorsum and tail after 20 minutes. Therefore, in the current study, we examined the tibia bone marrow, which is likely to respond to circulating PGE2.
  
  
  METHODS
  Right maxillary first molars were removed from retired female breeder rats in both the LIPUS and the control groups. LIPUS was applied extrabuccally to the socket every 24 hours for 2 weeks starting one day after extraction. Removed bone samples were fixed with 4% formaldehyde to prepare undecalcified frozen sections using Kawamoto's method for immunohistochemical or histochemical staining. Bone marrow samples dissected from the tibia were treated with RNAlater (Ambion) for later RT-PCR analysis.
  
  
  CONCLUSIONS
  Chemokine receptor CXCR4-positive bone marrow cells increased in the tibia of the LIPUS-treated rat. Together with ubiquitously expressed CXCL12(SDF-1), it is suggested that PGE2 released from the exposed socket is responsible for the recruitment, proliferation and mobilization of the precursors of bone forming cells. LIPUS is thought to exert humoral effects by recruiting bone marrow cells into the healing socket along with VEGF/angiogenesis induced by PGE2.
authors.affiliation: *Department of Oral Function and Restoration, Division of Periodontology; †Department of Oral Sciences; ‡Department of Neuroanatomy, Histology and Embryology; §Department of Oral and Maxillofacial Rehabilitation; ‖Department of Radiopraxis Science; ¶Department of Oral Sciences, Divisions of Dentistry of Circulation Control; and **Molecular and Cellular Biology of Mineralized Tissues, Kanagawa Dental University Graduate School of Dentistry.
authors.forename: Kouki
authors.initials: K
authors.lastname: Hidaka
authors.forename: Chihiro
authors.initials: C
authors.lastname: Miyamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Kawata
authors.forename: Makiko
authors.initials: M
authors.lastname: Saita
authors.forename: Ryota
authors.initials: R
authors.lastname: Kawamata
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Maehata
authors.forename: Masato
authors.initials: M
authors.lastname: Minabe
authors.forename: Satoko W
authors.initials: SW
authors.lastname: Takahashi
authors.forename: Shun-Suke
authors.initials: SS
authors.lastname: Takahashi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mikuni-Takagaki