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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #243067
Title: Restoration of regenerative osteoblastogenesis in aged mice: Modulation of TNF

Author
item WAHL, ELIZABETH - Arkansas Children'S Hospital
item ARONSON, JAMES - Arkansas Children'S Hospital
item LIU, LICHU - Arkansas Children'S Hospital
item FOWLKES, JOHN - Arkansas Children'S Hospital
item THRAILKILL, KATHRYN - Arkansas Children'S Nutrition Research Center (ACNC)
item BUNN, ROBERT - Arkansas Children'S Nutrition Research Center (ACNC)
item SKINNER, ROBBERT - Arkansas Children'S Hospital
item MILLER, MIKE - Arkansas Children'S Hospital
item COCKRELL, GAEL - Arkansas Children'S Hospital
item CLARK, LINDSEY - Arkansas Children'S Hospital
item OU, YANG - Arkansas Children'S Hospital
item ISALES, CARLOS - Arkansas Children'S Hospital
item BADGER, THOMAS - Arkansas Children'S Nutrition Research Center (ACNC)
item RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)
item SIMS, JOHN - Arkansas Children'S Hospital
item LUMPKIN, CHARLES - Arkansas Children'S Hospital

Submitted to: Journal of Bone and Mineral Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2009
Publication Date: 1/15/2010
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.