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Metabolic activation stimulates acid secretion and expression of matrix degrading proteases in human osteoblasts
  1. M George1,
  2. B Stein1,
  3. O Müller2,
  4. M Weis-Klemm2,
  5. T Pap3,
  6. W J Parak1,
  7. W K Aicher2
  1. 1Institute for Applied Physics and Centre for Nanoscience, Ludwig-Maximilians, University Munich, Munich, Germany
  2. 2Centre for Orthopaedic Surgery, University of Tübingen Medical School, Tübingen, Germany
  3. 3Department of Internal Medicine, University of Magdeburg, Magdeburg, Germany
  1. Correspondence to:
    Dr W K Aicher
    Research Laboratories, Centre for Orthopaedic Surgery, The University of Tübingen Medical School, Pulvermühlstrasse 5, D 72070 Tübingen, Germany; aicheruni-tuebingen.de

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.

Objectives: 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.

Conclusion: 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.

  • bone metabolism
  • metabolic activation
  • osteoblasts
  • pericellular acidification
  • proton secretion
  • BMP, bone morphogenic protein
  • MMP, matrix metalloproteinase
  • PMA, phorbol myristate acetate
  • RT-PCR, reverse transcriptase-polymerase chain reaction
  • TNFα, tumour necrosis factor α

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