Involvement of adenosine 5'-triphosphate in ultrasound-induced fracture repair.
Ultrasound (US) accelerates fracture healing; however, the mechanism of this effect remains unclear. Adenosine 5'-triphosphate (ATP) stimulates bone remodeling and is released constitutively from intact osteoblasts; this is a process that is enhanced after mechanical stimulation. We hypothesized that ATP release from osteoblasts is increased after US stimulation and that this leads to accelerated fracture healing. US was applied to SaOS-2 human osteoblasts and the concentration of ATP in the cell culture medium was determined. Cell proliferation and gene expression were subsequently investigated. Increased concentrations of ATP were detected in the culture medium of US-treated cells and both ATP and US stimulation caused increased receptor activator of nuclear factor-kappa B ligand (RANKL), decreased osteoprotegerin expression and increased cell proliferation by SaOS-2 cells. These findings indicate that US causes ATP release by osteoblasts in vitro and that this may contribute to accelerated fracture healing by enhancing osteoblast proliferation and increasing RANKL expression and decreasing osteoprotegerin expression by osteoblasts to promote osteoclastogenesis.
Hayton
Michael J
MJ
Wrightington Hospital, Lancashire, UK.
Dillon
Jane P
JP
Glynn
Danielle
D
Curran
Judith M
JM
Gallagher
James A
JA
Buckley
Katherine A
KA
D000255:Adenosine Triphosphate / Q000378:metabolism*; D016723:Bone Remodeling / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media; D017102:Fracture Healing / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000235:genetics; D016762:Genes, fos / Q000235:genetics; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D014464:Ultrasonic Therapy / Q000379:methods*
D002352:Carrier Proteins; D003470:Culture Media; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D000255:Adenosine Triphosphate