Restoration of regenerative osteoblastogenesis in aged mice: modulation of TNF.
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.
Wahl
Elizabeth C
EC
Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
Aronson
James
J
Liu
Lichu
L
Fowlkes
John L
JL
Thrailkill
Kathryn M
KM
Bunn
Robert C
RC
Skinner
Robert A
RA
Miller
Mike J
MJ
Cockrell
Gael E
GE
Clark
Lindsey M
LM
Ou
Yang
Y
Isales
Carlos M
CM
Badger
Thomas M
TM
Ronis
Martin J
MJ
Sims
John
J
Lumpkin
Charles K
CK
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
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