title: Restoration of regenerative osteoblastogenesis in aged mice: modulation of TNF.
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 alpha (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.
authors: Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
authors: Elizabeth C
authors: EC
authors: Wahl
authors: James
authors: J
authors: Aronson
authors: Lichu
authors: L
authors: Liu
authors: John L
authors: JL
authors: Fowlkes
authors: Kathryn M
authors: KM
authors: Thrailkill
authors: Robert C
authors: RC
authors: Bunn
authors: Robert A
authors: RA
authors: Skinner
authors: Mike J
authors: MJ
authors: Miller
authors: Gael E
authors: GE
authors: Cockrell
authors: Lindsey M
authors: LM
authors: Clark
authors: Yang
authors: Y
authors: Ou
authors: Carlos M
authors: CM
authors: Isales
authors: Thomas M
authors: TM
authors: Badger
authors: Martin J
authors: MJ
authors: Ronis
authors: John
authors: J
authors: Sims
authors: Charles K
authors: CK
authors: Lumpkin
mesh_terms: D000375:Aging / Q000097:blood / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000172:deficiency; D016207:Cytokines / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D011859:Radiography; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000494:pharmacology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects*; D012995:Solubility / Q000187:drug effects; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016207:Cytokines; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha