The overall project goals are development of Raman imaging with application to changes in bone mineral crystallite lattice and matrix collagen secondary structure in tissue subjected to tensile and compressive loading. Line-focused 532 nm laser light will be used to excite spectra of tissue pretreated by chemical and photochemical bleaching of fluorophores. An imaging spectrograph and low-light level CCD will provide spatially resolved spectra and ability to measure 0.1-0.2 cm(-1) changes peak in position with integration times as low as 0.05 sec. The project is the first phase of a study of the failure mechanism of osteoporotic tissue at the level of atomic and molecular structure, with the goal of new intervention strategies for minimization of fracture risk. The project will also serve as a model for study of biomechanics and other metabolic diseases and genetic defects of musculoskeletal tissue. Techniques will be developed using bovine bone and then ported to archived human tissue specimens. Our hypotheses are: Ion spacing in bone mineral change under mechanical stress during elastic deformation, while plastic deformation (cracking, compression or fracture) results in permanent changes 2) The matrix responds to mechanical stress in the elastic regime by perturbation of cross-links and changes in helix pitch of the strands of the collagen fibrils, resulting in changes in helix and coil conformations and hydrogen bonding. In plastic deformation cross-links between collagen fibrils are ruptured. These hypotheses can be tested by spectroscopic imaging of tissue because vibratioal frequencies and intensities respond to changes in local environment. Static Raman imaging will explore chemistry of tissue that has been subjected to fatigue loading. Dynamic imaging will follow changes in bone tissue chemical parameters with applied loads. Both univariate and multivariate methods will be used for data reduction. Systematic studies of age effects will be performed on murine tissue with exploratory work on human tissue at age extremes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR052010-01
Application #
6852532
Study Section
Special Emphasis Panel (ZRG1-MEDI (90))
Program Officer
Lester, Gayle E
Project Start
2005-01-07
Project End
2008-11-30
Budget Start
2005-01-07
Budget End
2005-11-30
Support Year
1
Fiscal Year
2005
Total Cost
$313,663
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Friedman, Michael A; Szczepankiewicz, Robert P; Kohn, David H (2018) Combined mineral-supplemented diet and exercise increases bone mass and strength after eight weeks and maintains increases after eight weeks detraining in adult mice. PLoS One 13:e0204470
Agarwal, Shailesh; Lloyd, William R; Loder, Shawn J et al. (2017) Combined reflectance and Raman spectroscopy to assess degree of in vivo angiogenesis after tissue injury. J Surg Res 209:174-177
Mroue, Kamal H; Xu, Jiadi; Zhu, Peizhi et al. (2016) Selective detection and complete identification of triglycerides in cortical bone by high-resolution (1)H MAS NMR spectroscopy. Phys Chem Chem Phys 18:18687-91
Oest, Megan E; Gong, Bo; Esmonde-White, Karen et al. (2016) Parathyroid hormone attenuates radiation-induced increases in collagen crosslink ratio at periosteal surfaces of mouse tibia. Bone 86:91-97
Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D et al. (2016) Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age. Bone 84:222-229
Friedman, Michael A; Bailey, Alyssa M; Rondon, Matthew J et al. (2016) Calcium- and Phosphorus-Supplemented Diet Increases Bone Mass after Short-Term Exercise and Increases Bone Mass and Structural Strength after Long-Term Exercise in Adult Mice. PLoS One 11:e0151995
Demers, Jennifer-Lynn H; Esmonde-White, Francis W L; Esmonde-White, Karen A et al. (2015) Next-generation Raman tomography instrument for non-invasive in vivo bone imaging. Biomed Opt Express 6:793-806
Mroue, Kamal H; Nishiyama, Yusuke; Kumar Pandey, Manoj et al. (2015) Proton-Detected Solid-State NMR Spectroscopy of Bone with Ultrafast Magic Angle Spinning. Sci Rep 5:11991
Lloyd, William R; Agarwal, Shailesh; Nigwekar, Sagar U et al. (2015) Raman spectroscopy for label-free identification of calciphylaxis. J Biomed Opt 20:80501
Mroue, Kamal H; Zhang, Rongchun; Zhu, Peizhi et al. (2014) Acceleration of natural-abundance solid-state MAS NMR measurements on bone by paramagnetic relaxation from gadolinium-DTPA. J Magn Reson 244:90-7

Showing the most recent 10 out of 28 publications