Matrix metalloproteinase-9 is a diagnostic marker of heterotopic ossification in a murine model

Eric Rodenberg, Ali Azhdarinia, Zawaunyka W. Lazard, Mary Hall, Sun Kuk Kwon, Nathaniel Wilganowski, Elizabeth A. Salisbury, Maria Merched-Sauvage, Elizabeth A. Olmsted-Davis, Eva M. Sevick-Muraca, Alan R. Davis

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Heterotopic ossification (HO) is a serious disorder that occurs when there is aberrant bone morphogenic protein (BMP) signaling in soft tissues. Currently, there are no methods to detect HO before mineralization occurs. Yet once mineralization occurs, there are no effective treatments, short of surgery, to reverse HO. Herein, we used in vivo molecular imaging and confirmatory ex vivo tissue analyses of an established murine animal model of BMP-induced HO to show that matrix metalloproteinase-9 (MMP-9) can be detected as an early-stage biomarker before mineralization. Ex vivo analyses show that active MMP-9 protein is significantly elevated within tissues undergoing HO as early as 48h after BMP induction, with its expression co-localizing to nerves and vessels. In vivo molecular imaging with a dual-labeled near-infrared fluorescence and micro-positron emission tomography (μPET) agent specific to MMP-2/-9 expression paralleled the ex vivo observations and reflected the site of HO formation as detected from microcomputed tomography 7 days later. The results suggest that the MMP-9 is a biomarker of the early extracellular matrix (ECM) re-organization and could be used as an in vivo diagnostic with confirmatory ex vivo tissue analysis for detecting HO or conversely for monitoring the success of tissue-engineered bone implants that employ ECM biology for engraftment.

Original languageEnglish (US)
Pages (from-to)2487-2496
Number of pages10
JournalTissue Engineering - Part A
Volume17
Issue number19-20
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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    Rodenberg, E., Azhdarinia, A., Lazard, Z. W., Hall, M., Kwon, S. K., Wilganowski, N., Salisbury, E. A., Merched-Sauvage, M., Olmsted-Davis, E. A., Sevick-Muraca, E. M., & Davis, A. R. (2011). Matrix metalloproteinase-9 is a diagnostic marker of heterotopic ossification in a murine model. Tissue Engineering - Part A, 17(19-20), 2487-2496. https://doi.org/10.1089/ten.tea.2011.0007