Restoration of regenerative osteoblastogenesis in aged mice: Modulation of TNF

Elizabeth C. Wahl, James Aronson, Lichu Liu, John L. Fowlkes, Kathryn M. Thrailkill, Robert C. Bunn, Robert A. Skinner, Mike J. Miller, Gael E. Cockrell, Lindsey M. Clark, Yang Ou, Carlos M. Isales, Thomas M. Badger, Martin J. Ronis, John Sims, Charles K. Lumpkin

Research output: Contribution to journalArticle

47 Scopus citations

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 a (TNF-α). 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.

Original languageEnglish (US)
Pages (from-to)114-123
Number of pages10
JournalJournal of Bone and Mineral Research
Volume25
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Aging
  • Bone repair
  • Cytokine
  • TNF

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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    Wahl, E. C., Aronson, J., Liu, L., Fowlkes, J. L., Thrailkill, K. M., Bunn, R. C., Skinner, R. A., Miller, M. J., Cockrell, G. E., 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. https://doi.org/10.1359/jbmr.090708