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 Articles76
  • Ketcham, P. D., Imholt, F., Yan, M., Smith, H. M., Asrar, S., Yu, L., ... Dawson, L. A. (2023). Microcomputed tomography staging of bone histolysis in the regenerating mouse digit.. Wound Repair Regen. 31(1), 17-27.
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  • Wagner, B. M., Robinson, J. W., Prickett, T., Espiner, E. A., Khosla, S., Gaddy, D., Suva, L. J., & Potter, L. R. (2022). Guanylyl Cyclase-B Dependent Bone Formation in Mice is Associated with Youth, Increased Osteoblasts, and Decreased Osteoclasts.. Calcif Tissue Int. 111(5), 506-518.
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  • Mohamed, F. F., Chavez, M. B., Huggins, S., Bertels, J., Falck, A., Suva, L. J., Foster, B. L., & Gaddy, D. (2022). Dentoalveolar Defects of Hypophosphatasia are Recapitulated in a Sheep Knock-In Model.. J Bone Miner Res. 37(10), 2005-2017.
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  • Stenhouse, C., Halloran, K. M., Hoskins, E. C., Newton, M. G., Moses, R. M., Seo, H., ... Bazer, F. W. (2022). Effects of exogenous progesterone on the expression of mineral regulatory molecules by ovine endometrium and placentomes.. Biol Reprod. 106(6), 1126-1142.
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  • Stenhouse, C., Halloran, K. M., Moses, R. M., Seo, H., Gaddy, D., Johnson, G. A., ... Bazer, F. W. (2022). Effects of progesterone and interferon tau on ovine endometrial phosphate, calcium, and vitamin D signaling.. Biol Reprod. 106(5), 888-899.
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Conference Papers29
  • Sherman, K., Falck, A., Huggins, S., Zimmel, K., Muneoka, K., Gaddy, D., Suva, L., & Dawson, L. (2022). Delayed Bone Regeneration in Down Syndrome Mice following P3 Digit Amputation. JOURNAL OF BONE AND MINERAL RESEARCH. 37, 220-220.
  • Stenhouse, C., Halloran, K., Hoskins, E., Moses, R., Seo, H., Dunlap, K., ... Bazer, F. (2022). Exogenous Progesterone in Early Pregnancy has Programming Effects on Phosphate, Calcium, and Vitamin D Signaling in the Ovine Endometrium and Placenta in Late Pregnancy. JOURNAL OF BONE AND MINERAL RESEARCH. 37, 109-109.
  • Sherman, K., Falck, A., Huggins, S., Zimmel, K., Muneoka, K., Gaddy, D., Dawson, L., & Suva, L. (2022). Impaired Fracture Healing in Dp16 Down Syndrome Mice. JOURNAL OF BONE AND MINERAL RESEARCH. 37, 219-219.
  • Brunauer, R., Xia, I., Dawson, L., Gaddy, D., Suva, L., & Muneoka, K. (2022). Mouse digit bone regeneration: A new model to study cell-specific effects of aging on bone repair. JOURNAL OF BONE AND MINERAL RESEARCH. 37, 19-19.
  • Brunauer, R., Xia, I., Dawson, L., Gaddy, D., Suva, L., & Muneoka, K. (2022). Mouse digit bone regeneration: A new model to study cell-specific effects of aging on bone repair. JOURNAL OF BONE AND MINERAL RESEARCH. 37, 255-255.
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