overview

My laboratory has been engaged in multiple areas of NIH-funded musculoskeletal research since 1996. We were the first to identify the non-steroidal gonadal inhibin hormones in regulating the hypothalamic-pituitary-gonadal-skeletal axis in mice, and the role of changes in inhibins that signal the onset of menopause (reproductive aging) to the onset of increasing bone turnover. We also demonstrated the anabolic effect of continual Inhibin exposure in normal mice and in bone repair. Our cellular focus on Inhibins and the related factor, Activin A revealed that Activin A suppresses local bone resorption through suppression of osteoclast formation, motility and survival. Our ongoing work is in the area of specific inhibin/betaglycan receptor interactions that mediate the effects on bone cells. We are also greatly interested in improving the low bone mass that we were the first to identify in both humans with Down Syndrome (DS) and in mouse models of DS as a low bone turnover disease. Our current NIH-funded research is working to identify the mechanisms of reduced fracture healing and compromised bone regeneration in Down Syndrome. We have demonstrated the efficacy of both PTH and SclAb in DS, and are now actively testing nutriceuticals to increase bone mass in mouse models of Down Syndrome. The limitations of using mouse models to study bone disease led us to our most recent and exciting endeavors in collaboration with TAMU experts in reproduction and embryo transfer technologies to develop a large platform model of bone disease, using sheep. We have generated the first large animal model of hypophosphatasia (HPP) via high efficiency gene editing of a knock-in point mutation in the ALPL gene, whose musculoskeletal and dental phenotypes are consistent with human HPP. We are now using this model to determine the etiology of mineralization deficiencies, muscle weakness and premature tooth loss by analysis of longitudinal biopsies and analysis of muscle, bone and dental specimens using CT, microCT, mechanical testing, immunohistochemistry, histomorphometry and ex vivo bone marrow cultures.

selected publications
Academic Articles64
  • Dolan, C. P., Imholt, F., Yang, T., Bokhari, R., Gregory, J., Yan, M., ... Muneoka, K. (2022). Mouse Digit Tip Regeneration Is Mechanical Load Dependent. Journal of Bone and Mineral Research. 37(2), 312-322.
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  • Stenhouse, C., Halloran, K. M., Newton, M. G., Gaddy, D., Suva, L. J., & Bazer, F. W. (2021). Novel mineral regulatory pathways in ovine pregnancy: II. Calcium-binding proteins, calcium transporters, and vitamin D signaling.. Biol Reprod. 105(1), 232-243.
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  • Stenhouse, C., Halloran, K. M., Newton, M. G., Gaddy, D., Suva, L. J., & Bazer, F. W. (2021). Novel mineral regulatory pathways in ovine pregnancy: I. phosphate, klotho signaling, and sodium-dependent phosphate transporters.. Biol Reprod. 104(5), 1084-1096.
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  • Kramer, K., Chavez, M. B., Tran, A. T., Farah, F., Tan, M. H., Kolli, T. N., ... Foster, B. L. (2021). Dental defects in the primary dentition associated with hypophosphatasia from biallelic ALPL mutations.. Bone. 143, 115732-115732.
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  • Suva, L. J., Cooper, A., Watts, A. E., Ebetino, F. H., Price, J., & Gaddy, D. (2021). Bisphosphonates in veterinary medicine: The new horizon for use.. Bone. 142, 115711-115711.
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Conference Papers23
  • Bertels, J., Chavez, M., Falck, A., Huggins, S., Kramer, K., Long, C., ... Gaddy, D. (2020). Consistent Dental Defects Associated with ALPL Mutations in Humans and Sheep with Hypophosphatasia. JOURNAL OF BONE AND MINERAL RESEARCH. 35, 303-303.
  • Stenhouse, C., Halloran, K. M., Newton, M. G., Gaddy, D., Suva, L. J., & Bazer, F. W. (2020). FGF and Klotho Phosphate Regulatory Pathways Linking Placenta and Bone. JOURNAL OF BONE AND MINERAL RESEARCH. 35, 41-41.
  • Bertels, J., Falck, A., Huggins, S., White, S., Long, C., Suva, L., & Gaddy, D. (2020). Impaired Mitochondrial Respiration and Altered Fiber Type in Hlypophosphatasia Sheep Skeletal Muscle. JOURNAL OF BONE AND MINERAL RESEARCH. 35, 304-304.
  • Sherman, K., Falck, A., Huggins, S., Dawson, L. A., Muneoka, K., Gaddy, D., Maden, M., & Suva, L. J. (2020). Sex Differences in the Skeletal Phenotype of the African Spiny Mouse (Acomys cahirinus). JOURNAL OF BONE AND MINERAL RESEARCH. 35, 167-167.
  • Bertels, J., Sherman, K., Falck, A., Huggins, S., Skenandore, C., Long, C., ... Gaddy, D. (2019). Differential muscle fiber typing and energetics defines a muscle weakness phenotype in HPP sheep. JOURNAL OF BONE AND MINERAL RESEARCH. 34, 273-273.
Email
dgaddy@tamu.edu
First Name
Dana
Last Name
Gaddy
mailing address
Texas A&M University; Veterinary Integrative Biosciences; 4458 TAMU
College Station, TX 77843-4458
USA