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United States Department of Agriculture

Agricultural Research Service

Research Project: IMPACT OF EARLY DIETARY FACTORS ON CHILD DEVELOPMENT AND HEALTH Title: Restoration of regenerative osteoblastogenesis in aged mice: Modulation of TNF

Authors
item Wahl, Elizabeth -
item Aronson, James -
item Liu, Lichu -
item Fowlkes, John -
item Thrailkill, Kathryn -
item Bunn, Robert -
item Skinner, Robbert -
item Miller, Mike -
item Cockrell, Gael -
item Clark, Lindsey -
item Ou, Yang -
item Isales, Carlos -
item Badger, Thomas -
item Ronis, Martin -
item Sims, John -
item Lumpkin, Charles -

Submitted to: Journal of Bone and Mineral Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 18, 2009
Publication Date: January 15, 2010
Citation: Wahl, E.C., Aronson, J., Liu, L., Fowlkes, J.L., Thrailkill, K.M., Bunn, R.C., Skinner, R.A., Miller, M.J., Cockrell, G., Clark, L.M., Ou, Y., Isales, C.M., Badger, T.M., Ronis, M.J., Sims, J., Lumpkin, C.K. 2010. Restoration of regenerative osteoblastogenesis in aged mice: Modulation of TNF. Journal of Bone and Mineral Research. 25(1):114-123.

Interpretive Summary: The results of this study demonstrate that poorly healing fractures in elderly patients can be treated successfully with an already FDA approved drug.

Technical Abstract: Skeletal changes accompanying aging are associated with both increased risk of fractures and impaired fracture healing, which, in turn, is due to compromised bone regeneration potential. These changes are associated with increased serum levels of selected proinflammatory cytokines, e.g., tumor necrosis factor (TNF alpha). We have used a unique model of bone regeneration to demonstrate (1) that aged-related deficits in direct bone formation can be restored to young mice by treatment with TNF blockers and (2) that the cyclin-dependent kinase inhibitor p21 is a candidate for mediation of the osteoinhibitory effects of TNF. It has been hypothesized recently that TNF antagonists may represent novel anabolic agents, and we believe that the data presented here represent a successful test of this hypothesis.

Last Modified: 12/20/2014