The ultimate goal of our research is to lower the number of bone fractures associated with osteoporosis, diabetes, cancer, and aging.

Towards that end, we investigate ways to improve the clinical assessment of fracture risk and identify regulators of bone toughness (lack of brittleness). Specifically, we hypothesize that the functional state of water in bone explains the disproportionate increase in fracture risk that occurs with aging and certain diseases. Ongoing projects include i) determining whether matrix-bound water and pore water, as measured by 1H Nuclear Magnetic Resonance (akin to MRI), can explain age- and diabetes-related decreases in bone’s resistance to fracture and ii) identifying the determinants of matrix-bound water.

In addition, we are developing polarization Raman Spectroscopy techniques to assess tissue heterogeneity as a potential biomarker of bone fragility.

In collaboration with material scientists at the University of Tennessee, Knoxville, we are assessing the relative contribution of nanoindentation and microindentation properties to bone’s ability to resist crack propagation with emphasis on viscoelastic energy dissipation and elastic energy release, respectively.

Lastly, using normal and genetically modified mice with and without drug treatments, we also study how advanced glycation end-products (AGEs), matrix proteins, transcription factors, and growth factors affect bone toughness and fracture resistance in general. Specifically, on-going projects include i) the effect of inhibiting transforming growth factor beta on the tissue-level properties of bone (beyond bone size), ii) the effect of AGE inhibitors on ameliorating the deleterious changes to bone caused by aging or diabetes, and iii) the role of activating transcription factor 4 in bone toughness.

Publications

Featured publications

  1. Bone collagen network integrity and transverse fracture toughness of human cortical bone. Willett TL, Dapaah DY, Uppuganti S, Granke M, Nyman JS (2019) Bone : 187-193
    › Primary publication · 30394355 (PubMed) · PMC6360115 (PubMed Central)
  2. Settable polymer/ceramic composite bone grafts stabilize weight-bearing tibial plateau slot defects and integrate with host bone in an ovine model. Lu S, McGough MAP, Shiels SM, Zienkiewicz KJ, Merkel AR, Vanderburgh JP, Nyman JS, Sterling JA, Tennent DJ, Wenke JC, Guelcher SA (2018) Biomaterials : 29-45
    › Primary publication · 29960822 (PubMed) · PMC6065109 (PubMed Central)
  3. Unexpected timely fracture union in matrix metalloproteinase 9 deficient mice. Yuasa M, Saito M, Molina C, Moore-Lotridge SN, Benvenuti MA, Mignemi NA, Okawa A, Yoshii T, Schwartz HS, Nyman JS, Schoenecker JG (2018) PLoS One 13(5): e0198088
    › Primary publication · 29851987 (PubMed) · PMC5978876 (PubMed Central)
  4. The Role of Matrix Composition in the Mechanical Behavior of Bone. Unal M, Creecy A, Nyman JS (2018) Curr Osteoporos Rep 16(3): 205-215
    › Primary publication · 29611037 (PubMed) · PMC5948175 (PubMed Central)
  5. Assessing glycation-mediated changes in human cortical bone with Raman spectroscopy. Unal M, Uppuganti S, Leverant CJ, Creecy A, Granke M, Voziyan P, Nyman JS (2018) J Biophotonics 11(8): e201700352
    › Primary publication · 29575566 (PubMed) · PMC6231413 (PubMed Central)
  6. Low bone toughness in the TallyHO model of juvenile type 2 diabetes does not worsen with age. Creecy A, Uppuganti S, Unal M, Clay Bunn R, Voziyan P, Nyman JS (2018) Bone : 204-214
    › Primary publication · 29438824 (PubMed) · PMC5878744 (PubMed Central)
  7. Daily parathyroid hormone administration enhances bone turnover and preserves bone structure after severe immobilization-induced bone loss. Harlow L, Sahbani K, Nyman JS, Cardozo CP, Bauman WA, Tawfeek HA (2017) Physiol Rep 5(18)
    › Primary publication · 28963125 (PubMed) · PMC5617932 (PubMed Central)
  8. Preserving and restoring bone with continuous insulin infusion therapy in a mouse model of type 1 diabetes. Nyman JS, Kalaitzoglou E, Clay Bunn R, Uppuganti S, Thrailkill KM, Fowlkes JL (2017) Bone Rep : 1-8
    › Primary publication · 28736738 (PubMed) · PMC5508511 (PubMed Central)
  9. Applying Full Spectrum Analysis to a Raman Spectroscopic Assessment of Fracture Toughness of Human Cortical Bone. Makowski AJ, Granke M, Ayala OD, Uppuganti S, Mahadevan-Jansen A, Nyman JS (2017) Appl Spectrosc 71(10): 2385-2394
    › Primary publication · 28708001 (PubMed) · PMC5561524 (PubMed Central)
  10. 30-Second bound and pore water concentration mapping of cortical bone using 2D UTE with optimized half-pulses. Manhard MK, Harkins KD, Gochberg DF, Nyman JS, Does MD (2017) Magn Reson Med 77(3): 945-950
    › Primary publication · 28090655 (PubMed) · PMC5526671 (PubMed Central)

Community Leaders

Contact Information

1161 21st Avenue South
Medical Center Drive
B-0213 Medical Center North (MCN)
Nashville, TN 37232
United States
6153227184 (p)

Sasidhar Uppuganti
6153227184 (p)
Email

Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

Aged biomechanics Body Weight Bone Bone Cements Bone Matrix Bound water Cercopithecus aethiops Chromatography, High Pressure Liquid Cortical Bone Extracellular Matrix Fractures, Bone Glycation End Products, Advanced Haversian System Matrix Metalloproteinase 2 micro-CT nuclear magnetic resonance orthopaedics Osteocytes Osteogenesis Raman spectroscopy Spectrum Analysis, Raman Streptozocin Sympathetic Nervous System Tensile Strength TOR Serine-Threonine Kinases Up-Regulation