Premium
Restoration of regenerative osteoblastogenesis in aged mice: Modulation of TNF
Author(s) -
Wahl Elizabeth C,
Aronson James,
Liu Lichu,
Fowlkes John L,
Thrailkill Kathryn M,
Bunn Robert C,
Skinner Robert A,
Miller Mike J,
Cockrell Gael E,
Clark Lindsey M,
Ou Yang,
Isales Carlos M,
Badger Thomas M,
Ronis Martin J,
Sims John,
Lumpkin Charles K
Publication year - 2010
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.090708
Subject(s) - proinflammatory cytokine , tumor necrosis factor alpha , regeneration (biology) , endocrinology , medicine , anabolism , cancer research , biology , inflammation , microbiology and biotechnology
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 α (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. © 2010 American Society for Bone and Mineral Research