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. The role of ?CT 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 ?CT, 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.. 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. 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 (?CT 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 #
5P01DK011794-49
Application #
9170964
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
49
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Dedic, Christopher; Hung, Tin Shing; Shipley, Alan M et al. (2018) Calcium fluxes at the bone/plasma interface: Acute effects of parathyroid hormone (PTH) and targeted deletion of PTH/PTH-related peptide (PTHrP) receptor in the osteocytes. Bone 116:135-143
Mizuhashi, Koji; Ono, Wanida; Matsushita, Yuki et al. (2018) Resting zone of the growth plate houses a unique class of skeletal stem cells. Nature 563:254-258
Hanna, Patrick; Grybek, Virginie; Perez de Nanclares, Guiomar et al. (2018) Genetic and Epigenetic Defects at the GNAS Locus Lead to Distinct Patterns of Skeletal Growth but Similar Early-Onset Obesity. J Bone Miner Res 33:1480-1488
Wein, Marc N; Foretz, Marc; Fisher, David E et al. (2018) Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential. Trends Endocrinol Metab 29:723-735
Bastepe, Murat (2018) GNAS mutations and heterotopic ossification. Bone 109:80-85
Christov, Marta; Clark, Abbe R; Corbin, Braden et al. (2018) Inducible podocyte-specific deletion of CTCF drives progressive kidney disease and bone abnormalities. JCI Insight 3:
Roszko, Kelly L; Bi, Ruiye; Gorvin, Caroline M et al. (2017) Knockin mouse with mutant G?11 mimics human inherited hypocalcemia and is rescued by pharmacologic inhibitors. JCI Insight 2:e91079
Grigelioniene, Giedre; Nevalainen, Pasi I; Reyes, Monica et al. (2017) A Large Inversion Involving GNAS Exon A/B and All Exons Encoding Gs? Is Associated With Autosomal Dominant Pseudohypoparathyroidism Type Ib (PHP1B). J Bone Miner Res 32:776-783
Balani, Deepak H; Ono, Noriaki; Kronenberg, Henry M (2017) Parathyroid hormone regulates fates of murine osteoblast precursors in vivo. J Clin Invest 127:3327-3338
Cheloha, Ross W; Chen, Bingming; Kumar, Niyanta N et al. (2017) Development of Potent, Protease-Resistant Agonists of the Parathyroid Hormone Receptor with Broad ? Residue Distribution. J Med Chem 60:8816-8833

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