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dc.contributor.authorMailhiot, Sarah E.
dc.contributor.authorZignego, Donald L.
dc.contributor.authorPrigge, Justin R.
dc.contributor.authorWardwell, Ella R.
dc.contributor.authorSchmidt, Edward E.
dc.contributor.authorJune, Ronald K.
dc.date.accessioned2015-10-16T20:32:04Z
dc.date.available2015-10-16T20:32:04Z
dc.date.issued2015-07
dc.identifier.citationMailhiot, Sarah E., Donald L. Zignego, Justin R. Prigge, Ella R. Wardwell, Edward E. Schmidt, and Ronald K. June. "Non-Invasive Quantification of Cartilage Using a Novel In Vivo Bioluminescent Reporter Mouse." PLoS ONE 10, no. 7 (July 2015): e0130564. DOI:https://dx.doi.org/10.1371/journal.pone.0130564.en_US
dc.identifier.issn1932-6203
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/9327
dc.description.abstractMouse models are common tools for examining post-traumatic osteoarthritis (OA), which involves cartilage deterioration following injury or stress. One challenge to current mouse models is longitudinal monitoring of the cartilage deterioration in vivo in the same mouse during an experiment. The objective of this study was to assess the feasibility for using a novel transgenic mouse for non-invasive quantification of cartilage. Chondrocytes are defined by expression of the matrix protein aggrecan, and we developed a novel mouse containing a reporter luciferase cassette under the inducible control of the endogenous aggrecan promoter. We generated these mice by crossing a Cre-dependent luciferase reporter allele with an aggrecan creERT2 knockin allele. The advantage of this design is that the targeted knockin retains the intact endogenous aggrecan locus and expresses the tamoxifen-inducible CreERT2 protein from a second IRES-driven open reading frame. These mice display bioluminescence in the joints, tail, and trachea, consistent with patterns of aggrecan expression. To evaluate this mouse as a technology for non-invasive quantification of cartilage loss, we characterized the relationship between loss of bioluminescence and loss of cartilage after induction with (i) ex vivo collagenase digestion, (ii) an in vivo OA model utilizing treadmill running, and (iii) age. Ex vivo experiments revealed that collagenase digestion of the femur reduced both luciferase signal intensity and pixel area, demonstrating a link between cartilage degradation and bioluminescence. In an in vivo model of experimental OA, we found decreased bioluminescent signal and pixel area, which correlated with pathological disease. We detected a decrease in both bioluminescent signal intensity and area with natural aging from 2 to 13 months of age. These results indicate that the bioluminescent signal from this mouse may be used as a non-invasive quantitative measure of cartilage. Future studies may use this reporter mouse to advance basic and preclinical studies of murine experimental OA with applications in synovial joint biology, disease pathogenesis, and drug delivery.en_US
dc.description.sponsorshipMontana State University Vice President for Research; NIH P20GM10339405S1en_US
dc.rightsCC BY 4.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleNon-Invasive Quantification of Cartilage Using a Novel In Vivo Bioluminescent Reporter Mouseen_US
dc.typeArticleen_US
mus.citation.extentfirstpagee0130564en_US
mus.citation.issue7en_US
mus.citation.journaltitlePLoS ONEen_US
mus.citation.volume10en_US
mus.identifier.categoryChemical & Material Sciencesen_US
mus.identifier.categoryLife Sciences & Earth Sciences
mus.identifier.categoryHealth & Medical Sciences
mus.identifier.doi10.1371/journal.pone.0130564en_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.collegeCollege of Engineeringen_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentCell Biology & Neuroscience.en_US
mus.relation.departmentMechanical & Industrial Engineering.en_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.data.thumbpage9en_US


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