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. 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)
  2. 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)
  3. 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 : 3702817718149
    › Primary publication · 28708001 (PubMed)
  4. 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)
  5. The impact of SGLT2 inhibitors, compared with insulin, on diabetic bone disease in a mouse model of type 1 diabetes. Thrailkill KM, Nyman JS, Bunn RC, Uppuganti S, Thompson KL, Lumpkin CK, Kalaitzoglou E, Fowlkes JL (2016) Bone
    › Primary publication · 27989651 (PubMed)
  6. Technical note: Recommendations for a standard procedure to assess cortical bone at the tissue-level in vivo using impact microindentation. Diez-Perez A, Bouxsein ML, Eriksen EF, Khosla S, Nyman JS, Papapoulos S, Tang SY (2016) Bone Rep : 181-185
    › Primary publication · 27975078 (PubMed) · PMC5152622 (PubMed Central)
  7. Advances in imaging approaches to fracture risk evaluation. Manhard MK, Nyman JS, Does MD (2016) Transl Res
    › Primary publication · 27816505 (PubMed)
  8. Differences in sensitivity to microstructure between cyclic- and impact-based microindentation of human cortical bone. Uppuganti S, Granke M, Manhard MK, Does MD, Perrien DS, Lee DH, Nyman JS (2016) J Orthop Res
    › Primary publication · 27513922 (PubMed)
  9. Combined treatment with a transforming growth factor beta inhibitor (1D11) and bortezomib improves bone architecture in a mouse model of myeloma-induced bone disease. Nyman JS, Merkel AR, Uppuganti S, Nayak B, Rowland B, Makowski AJ, Oyajobi BO, Sterling JA (2016) Bone : 81-91
    › Primary publication · 27423464 (PubMed) · PMC4996753 (PubMed Central)
  10. Prevalent role of porosity and osteonal area over mineralization heterogeneity in the fracture toughness of human cortical bone. Granke M, Makowski AJ, Uppuganti S, Nyman JS (2016) J Biomech 49(13): 2748-2755
    › Primary publication · 27344202 (PubMed) · PMC5056137 (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 Collagen Type I Diphosphates Extracellular Matrix Extracellular Signal-Regulated MAP Kinases Fractures, Bone Matrix Metalloproteinase 2 micro-CT NF-KappaB Inhibitor alpha nuclear magnetic resonance orthopaedics Osteocytes Osteogenesis Raman spectroscopy Spectrum Analysis, Raman Streptozocin Sympathetic Nervous System Tensile Strength TOR Serine-Threonine Kinases Up-Regulation