title: Calcium signaling is required for ultrasound-stimulated aggrecan synthesis by rat chondrocytes.
abstract: Low-intensity ultrasound accelerates fracture healing in humans. In rat femur fracture models, ultrasound advanced healing is associated with increased proteoglycan expression. Here we report that ultrasound stimulation of primary rat chondrocytes elevated the intracellular concentration of calcium [Ca2+]i. The [Ca2+]i increase was rapid and transient at lower pressures (175-320 kPa), but rapid and sustained at higher ultrasound exposures (350-500 kPa). Chelating internal [Ca2+]i with 1,2-bis(2-aminophenoxy) ethane-N-N-N',N'-tetraacetic acid (BAPTA-AM), stopping the Ca2+/ATP-ase induced mitochondrial release of [Ca2+]i with Thapsigargin, or removing [Ca2+]i from the medium with EGTA inhibited the stimulatory effects of ultrasound on proteoglycan synthesis. These results imply that ultrasound-stimulated synthesis of cell matrix proteoglycan, associated with accelerated fracture healing, is mediated by intracellular calcium signaling.
authors.affiliation: Department of Orthopaedics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Javad
authors.initials: J
authors.lastname: Parvizi
authors.forename: Vladimir
authors.initials: V
authors.lastname: Parpura
authors.forename: James F
authors.initials: JF
authors.lastname: Greenleaf
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bolander
mesh_terms: D053674:Aggrecans; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins; D005110:Extracellular Space / Q000378:metabolism; D017102:Fracture Healing / Q000502:physiology; D037181:Lectins, C-Type; D008928:Mitochondria / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis*; D051381:Rats; D020318:Rats, Long-Evans; D019284:Thapsigargin / Q000494:pharmacology; D018084:Ultrasonography, Interventional
chemical_list: C508321:Acan protein, rat; D053674:Aggrecans; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D019284:Thapsigargin; D002118:Calcium