The core facility provides investigators in the Program Project access to technologies that would be otherwise inaccessible because of prohibitive cost of equipment (ie, microCT) and/or lack of expertise required for the conduct and interpretation of the assay (ie, histomorphometry, biomechanical testing). Therefore, despite the scientific value that these measurements bring to the studies proposed, few individual investigators would have access to this equipment and expertise. In the setting of a core facility, these assessments can be conducted in an organized fashion by experienced personnel, with cost and time savings passed on to investigators. In the past decade, skeletal imaging of murine models has improved markedly. In addition to 2D radiographs and areal bone mineral density measurements, high-resolution desktop imaging systems are used routinely to assess bone microarchitecture during early development as well as post-natal periods 3. The role of 1JCT is expanding rapidly, as it provides a non-destructive, high-resolution, true 3D evaluation of bone microarchitecture. The non-destructive nature of the technique means that following 1JCT, specimens can be assessed by numerous additional methods, including standard histologic and histomorphometric assessment to gain information on the cellular composition and activity, in situ hybridization (ISH) or immunohistochemistry (IHC) to determine the pattern of gene expression, or biomechanical testing to determine bone strength. Yet, to fully understand the skeletal consequences of genetic alterations or pharmacologic interventions, it is critical to assess structure-function relationships. A key element to assessing skeletal """"""""function"""""""" is biomechanical testing: """"""""the skeletal functional integrity can only be assessed by structural strength tests ... and conclusions regarding bone mechanical function based solely on geometry or bone mineral content are inappropriate and likely misleading.""""""""4 . Biomechanical testing has been employed for decades to assess bone strength and fragility. Yet, despite the known importance of this assay, along with well-established protocols, fewer than 30% of experimental studies published in key bone-oriented journals included whole bone strength testing 5. Whole bone strength testing, morphology and microarchitecture measurements are essential to characterize skeletal mechanical competence, while other assays, including serum biochemistry, histology, histomorphometry, immunohistochemistry and in situ hybridization provide information about the mechanisms that contribute to skeletal competence. The integration of these services into a core facility is significant as it provides efficient, high-quality metabolic and tissue phenotyping assays that are critical for all projects. Significance of the Core is also exemplified by the coordinated and sensible approach to assessment of serum markers of bone metabolism, basic skeletal/ renal phenotypes and responses to interventions. In vivo bone densitometry and various ex vivo assessments will be designed to provide complementary information. This will be achieved by assessing the same specimens with different ex vivo techniques (IJCT and biomechanical testing or histomorphometry) that provide unique, but complementary information about skeletal traits.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
2P01DK011794-46
Application #
8659701
Study Section
Special Emphasis Panel (ZDK1-GRB-J (O1))
Project Start
Project End
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
46
Fiscal Year
2014
Total Cost
$261,130
Indirect Cost
$110,545
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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