Title | Non-invasive optical detection of cathepsin K-mediated fluorescence reveals osteoclast activity in vitro and in vivo. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Kozloff KM, Quinti L, Patntirapong S, Hauschka PV, Tung C-H, Weissleder R, Mahmood U |
Journal | Bone |
Volume | 44 |
Issue | 2 |
Pagination | 190-8 |
Date Published | 2009 Feb |
ISSN | 1873-2763 |
Keywords | Animals, Animals, Newborn, Bone Development, Bone Resorption, Calcification, Physiologic, Cathepsin K, Cathepsins, Cell Survival, Cells, Cultured, Cryoultramicrotomy, Female, Femur, Fluorescence, Humans, Mice, Mice, Inbred BALB C, Molecular Probe Techniques, Molecular Probes, Osteoclasts, Ovariectomy, RNA, Messenger, Up-Regulation |
Abstract | Osteoclasts degrade bone matrix by demineralization followed by degradation of type I collagen through secretion of the cysteine protease, cathepsin K. Current imaging modalities are insufficient for sensitive observation of osteoclast activity, and in vivo live imaging of osteoclast resorption of bone has yet to be demonstrated. Here, we describe a near-infrared fluorescence reporter probe whose activation by cathepsin K is shown in live osteoclast cells and in mouse models of development and osteoclast upregulation. Cathepsin K probe activity was monitored in live osteoclast cultures and correlates with cathepsin K gene expression. In ovariectomized mice, cathepsin K probe upregulation precedes detection of bone loss by micro-computed tomography. These results are the first to demonstrate non-invasive visualization of bone degrading enzymes in models of accelerated bone loss, and may provide a means for early diagnosis of upregulated resorption and rapid feedback on efficacy of treatment protocols prior to significant loss of bone in the patient. |
DOI | 10.1016/j.bone.2008.10.036 |
Alternate Journal | Bone |
PubMed ID | 19007918 |
PubMed Central ID | PMC2656637 |
Grant List | T32-CA079443 / CA / NCI NIH HHS / United States R24-CA2872 / CA / NCI NIH HHS / United States U24 CA092782 / CA / NCI NIH HHS / United States T32 CA079443 / CA / NCI NIH HHS / United States R01 EB001872-04 / EB / NIBIB NIH HHS / United States R01 EB001872 / EB / NIBIB NIH HHS / United States U24 CA092782-07 / CA / NCI NIH HHS / United States R01EB001872 / EB / NIBIB NIH HHS / United States T32 CA079443-04 / CA / NCI NIH HHS / United States |
Related Institute:
Molecular Imaging Innovations Institute (MI3)