Matrix-metalloproteinase-9 is cleaved and activated by Cathepsin K

Abstract: Background: Matrix-metalloproteinases 9 (MMP-9) belongs to the class of matrix metalloproteinases whose main function is to degrade and remodel the extracellular matrix (ECM). MMP-9 has been shown to be an integral part of many diseases where modulation of the ECM is a key step such as cancer, osteoporosis and fibrosis. MMP-9 is secreted as a latent pro-enzyme that requires activation in the extracellular space. Therefore, identifying physiological and molecular contexts, which can activate MMP-9 is important.
Results: Acidification of osteoclast-conditioned media to pH 5 resulted in a fragment with a size corresponding to active MMP-9. Also, treatment of recombinant proMMP-9 with recombinant cathepsin K (CTSK) at pH 5 yielded a fragment that corresponded to the molecular weight of active MMP-9, and showed MMP-9 activity. This activation was abrogated in the presence of CTSK inhibitor indicating that CTSK was responsible for the activation of pro-MMP-9. Knocking down CTSK in MDA-MB-231 cells also diminished MMP-9 activity compared to wild type control.
Conclusions: Here we provide the first evidence that CTSK can cleave and activate MMP-9 in acidic environments such as seen in tumors and during bone resorption. This finding provides a key link between CTSK expression in tumors and bone and ECM remodeling, through MMP-9 activation. This novel mechanism to activate MMP-9 through extracellular physiological changes elucidated in this study reveals a protease-signaling network involving CTSK and MMP-9 and provides the impetus to explore ECM proteases as physiological markers and pharmacological targets

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: BMC research notes. 8 (2015), 322, DOI 10.1186/s13104-015-1284-8, issn: 1756-0500 ; IN COPYRIGHT http://rightsstatements.org/page/InC/1.0 rs

Classification and Topics

• Keyword: Enzymaktivierung ; Krebs ; Therapie ; Knochen ; Resorption ; Kathepsin H ; Onkologie

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2015
• Creator: Christensen, Jon Høj ; Shastri, V. Prasad
• Contributor: Albert-Ludwigs-Universität Freiburg. Institut für Makromolekulare Chemie ; Albert-Ludwigs-Universität Freiburg. Fakultät für Chemie und Pharmazie ; Albert-Ludwigs-Universität Freiburg. Centre for Biological Signalling Studies ; Albert-Ludwigs-Universität Freiburg

Further information

• DOI: 10.1186/s13104-015-1284-8
• URN: urn:nbn:de:bsz:25-freidok-125617
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:44 PM CET