The overall goal of the Tissue Phenotyping and Bone Metabolism Core, led by experienced investigators Drs. Bouxsein and Demay, is to provide the highest quality assessment of kidney and musculoskeletal tissues, as well as serum and urine biochemistry, in the most efficient manner. The core will provide investigators with access to state-of-the-art technology, training in use of new devices (as appropriate) and consultation on experimental design, protocol development, data analysis and interpretation. The core provides hierarchical, multi-scale assessment of musculoskeletal phenotypes in rodent models with genetic alterations, as well as dietary and pharmacologic interventions, allowing the efficient evaluation of tissue samples, with regard to both time and resources. Altogether the core has been highly effective in supporting the investigators in the Program Project, as evidenced by the use of the core by all projects, the efficient processing of specimens, and number of manuscripts to which the core contributed. In this renewal, the core will support all four proposed projects. In the current funding period, the core supported all the projects and will continue to do so by addressing the following three specific aims: 1) Provide access to state-of-the-art serum and urinary biochemical analyses; histologic & histomorphometric analyses; skeletal imaging & biomechanical assessments; 2) Promote a cost-effective, efficient, integrated, hierarchical approach to evaluation of tissue phenotypes; and 3) Support investigators by providing hands-on training, expert advice on study design, trouble shooting of new protocols/probes/antibodies and interpretation of results generated by the Core facility. With experienced leadership and technical staff, as well as state-of-the-art equipment and strict quality control measures, the core will achieve these aims by offering the following services, including: a variety of histologic techniques; quantitative histomorphometry; in vivo bone densitometry and body composition; high resolution bone microarchitecture measurements via micro-computed tomography; marrow fat quantification via osmium tetraoxide micro-computed tomography; whole bone and tissue level biomechanical testing; and serum and urine biochemistry relating to bone and kidney metabolism. By conducting these evaluations within the core facility, high quality control standards can be readily maintained. Moreover, the core will provide coordinated, timely assessments, and will assist investigators with study design and interpretation of results, as needed. Salaries of core personnel and basic supplies are covered in the Core budget, however user fees are collected for some services to offset expenses not covered in the core budget. We find that this hybrid approach, where salaries and basic supplies are covered by the core, but some services require users fees, results in a stable operation of the Core, with equitable resource sharing and cost allocation amongst the projects.

Public Health Relevance

The Tissue Phenotyping and Bone Metabolism Core, led by experienced investigators Drs. Bouxsein and Demay, provides the highest quality assessment of kidney and musculoskeletal tissues, as well as serum and urine biochemistry, in the most efficient manner to all Program Project investigators. Accordingly, the core provides investigators with access to state-of-the-art technology, training in use of new devices (as appropriate) and consultation on experimental design, protocol development, data analysis and interpretation. The core aims to provide hierarchical, multi-scale assessment of musculoskeletal and kidney phenotypes in rodent models with genetic alterations, as well as dietary and pharmacologic interventions, allowing the efficient evaluation of tissue samples, with regard to both time and resources.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
2P01DK011794-51A1
Application #
9793435
Study Section
Special Emphasis Panel (ZDK1)
Project Start
1997-08-01
Project End
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
51
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
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:
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
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

Showing the most recent 10 out of 215 publications