Form and function are intimately interrelated. However, the histological analyses of our target tissues (bone, cartilage, tendon, ligament, muscle) provide specialized challenges not often encountered when conducting these techniques on non-skeletal tissues. For example, due to the extensive extracellular matrix, these tissues can be very difficult to prepare and section, and bone presents a particular challenge due to mineralization. A specialized knowledge of the stages of development, and limb and joint morphology is necessary for the analysis of skeletal tissues. In addition to morphology, the localization of proteins and mRNA in mouse models of musculoskeletal diseases is a vital component in the analysis of the molecular mechanism of protein function, the response to injury, and disease. The overall objective of the In situ Molecular Analysis Core is to provide histological services for the identification and analysis of molecular phenotypes of our target tissues, bone, cartilage, muscle, tendon and ligament, in developing and adult mice. The services will include preparation of tissues and tissue sections;a reagent bank for histology, immunohistochemistry and in situ hybridization;and training in the techniques of in situ hybridization to mRNA, immunohistochemistry, deconvolution microscopy, and histomorphometry. Reagents for the analysis of mouse, and in some cases human, tissues will be available. We expect that the findings from mouse models will be extended to human disease and injury. The Director/Co-Directors and collaborating investigators will provide consultation and advice on analysis and interpretation of the target tissue phenotypes. Deconvolution microscopic analysis and bone histomorphometry will provide the opportunity to utilize sophisticated techniques and quantitative analysis not currently available to all investigators. The strength of this Core lies in the specific techniques developed for adult mice, sectioning delicate early healing tissue, and properly aligning blocks for sectioning of ligament and fracture healing, as well as the expertise in tissue staining by a wide variety of histochemical and molecular techniques. All aspects of the core provide collaboration, training, and education, which will strengthen ties among the research base and enhance the quality of the science performed. Thus, not only will this Core be cost-effective, it will allow scientists to explore skeletal phenotypes that they could not in any other way investigate. This core will complement the specific functional analyses proposed in Core B and the mouse models of Core D.

Public Health Relevance

The In Situ Molecular Analysis Core (C) will allow our scientists to maximize the amount of data derived from animal models of osteoporosis, arthritis, musculoskeletal injury, cancer metastasis to bone, and other musculoskeletal diseases by providing access to a number of sophisticated techniques and reagents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR057235-03
Application #
8246483
Study Section
Special Emphasis Panel (ZAR1)
Project Start
2011-04-01
Project End
2014-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
3
Fiscal Year
2011
Total Cost
$180,452
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Rohatgi, Nidhi; Zou, Wei; Collins, Patrick L et al. (2018) ASXL1 impairs osteoclast formation by epigenetic regulation of NFATc1. Blood Adv 2:2467-2477
Brophy, R H; Zhang, B; Cai, L et al. (2018) Transcriptome comparison of meniscus from patients with and without osteoarthritis. Osteoarthritis Cartilage 26:422-432
Sun, David; Brodt, Michael D; Zannit, Heather M et al. (2018) Evaluation of loading parameters for murine axial tibial loading: Stimulating cortical bone formation while reducing loading duration. J Orthop Res 36:682-691
Turecamo, S E; Walji, T A; Broekelmann, T J et al. (2018) Contribution of metabolic disease to bone fragility in MAGP1-deficient mice. Matrix Biol 67:1-14
Meyer, Gretchen A (2018) Evidence of induced muscle regeneration persists for years in the mouse. Muscle Nerve 58:858-862
Wang, Chun; Hockerman, Susan; Jacobsen, E Jon et al. (2018) Selective inhibition of the p38? MAPK-MK2 axis inhibits inflammatory cues including inflammasome priming signals. J Exp Med 215:1315-1325
Chinzei, N; Brophy, R H; Duan, X et al. (2018) Molecular influence of anterior cruciate ligament tear remnants on chondrocytes: a biologic connection between injury and osteoarthritis. Osteoarthritis Cartilage 26:588-599
Rai, Muhammad Farooq; Tycksen, Eric D; Sandell, Linda J et al. (2018) Advantages of RNA-seq compared to RNA microarrays for transcriptome profiling of anterior cruciate ligament tears. J Orthop Res 36:484-497
Chinzei, Nobuaki; Rai, Muhammad Farooq; Hashimoto, Shingo et al. (2018) Evidence for Genetic Contribution to Variation in Post-Traumatic Osteoarthritis in Mice. Arthritis Rheumatol :
Rai, Muhammad Farooq; Pham, Christine Tn (2018) Intra-articular drug delivery systems for joint diseases. Curr Opin Pharmacol 40:67-73

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