title: Metabolic activation stimulates acid secretion and expression of matrix degrading proteases in human osteoblasts.
abstract: BACKGROUND
  Both cellular and matrix components of healthy bone are permanently renewed in a balanced homoeostasis. Osteoclastic bone resorption involves the expression of vacuolar-type ATPase proton pumps (vATPase) on the outer cell membrane and the secretion of matrix degrading proteases. Osteoblasts modulate the deposition of bone mineral components and secrete extracellular matrix proteins.
  
  
  OBJECTIVE
  To investigate the ability of osteoblasts and osteosarcoma to secrete acid and express matrix degrading proteases upon metabolic activation. To examine also the potential contribution of vATPases to proton secretion expressed on osteoblasts.
  
  
  METHODS
  Osteoblasts were isolated from trabecular bone and characterised by reverse transcriptase-polymerase chain reaction and immunohistochemistry. Proton secretion was analysed by a cytosensor microphysiometer.
  
  
  RESULTS
  Osteoblasts not only express matrix degrading proteases upon stimulation with tumour necrosis factor or with phorbol ester but they also secrete protons upon activation. Proton secretion by osteoblasts is associated partially with proton pump ATPases.
  
  
  CONCLUSIONS
  These data suggest that, in addition to monocyte derived osteoclasts, cytokine activated mesenchymal osteoblasts and osteosarcoma cells may contribute to the acidic milieu required for bone degradation.
authors.affiliation: Institute for Applied Physics and Centre for Nanoscience, Ludwig-Maximilians, University Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: George
authors.forename: B
authors.initials: B
authors.lastname: Stein
authors.forename: O
authors.initials: O
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Weis-Klemm
authors.forename: T
authors.initials: T
authors.lastname: Pap
authors.forename: W J
authors.initials: WJ
authors.lastname: Parak
authors.forename: W K
authors.initials: WK
authors.lastname: Aicher
mesh_terms: D001711:Biotransformation; D001857:Bone Matrix / Q000201:enzymology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D012516:Osteosarcoma / Q000201:enzymology / Q000378:metabolism; D011522:Protons; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D011522:Protons; D014409:Tumor Necrosis Factor-alpha; D010450:Endopeptidases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D013755:Tetradecanoylphorbol Acetate