title: Distinct anabolic response of osteoblast to low-intensity pulsed ultrasound.
abstract: Low-intensity pulsed ultrasound, a form of mechanical energy transmitted as high-frequency acoustical pressure waves, provides noninvasive therapeutic treatment for accelerating fracture repair and distraction osteogenesis. Relatively young osteoblasts respond to ultrasound by transiently upregulating message levels of immediate-early genes as well as that of osteocalcin and insulin-like growth factor I (IGF-I). Osteocytes derived from newborn rat tibia and calvaria responded to a lesser extent only in c-fos and cyclooxygenase-2 (COX-2) messages. Compared with the stretched osteocytes, which use stretch-activated and parathyroid hormone (PTH)-potentiated Ca2+ influx as an entry route to the protein kinase A (PKA) signal transduction pathways, there was no evidence of Ca2+ internalization by any of the cells tested on exposure to the ultrasound. On the other hand, inhibitors of p38 mitogen-activated protein kinase (MAPK) and upstream phosphoinositide 3-kinase (PI3K) blocked COX-2 and osteocalcin upregulation by the ultrasound-exposed ST2, murine bone marrow-derived cells. This is distinct from the aforementioned osteocytic response to low-frequency stretching and implies the involvement of integrins. Our findings suggested that accelerated fracture repair and distraction osteogenesis by the low-intensity pulsed ultrasound depend, at least in part, on the stimulation of osteoblastic cells at relatively early stages of osteogenic lineage. Bone is under control of multiple regulatory mechanisms so that diverse physical forces can be reflected to the microenvironment of each cell, in turn, to the entire bone.
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Naruse
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Itoman
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mikuni-Takagaki
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051546:Cyclooxygenase 2; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010006:Osteoblasts / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D015675:Osteocalcin / Q000378:metabolism; D010011:Osteocytes / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012886:Skull / Q000378:metabolism; D013977:Tibia / Q000378:metabolism; D013997:Time Factors; D014465:Ultrasonics; D014463:Ultrasonography; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D018931:Antineoplastic Agents, Hormonal; D007527:Isoenzymes; D016760:Proto-Oncogene Proteins c-fos; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D002118:Calcium