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 language | English (US) |
|---|---|
| Pages (from-to) | 114-123 |
| Number of pages | 10 |
| Journal | Journal of Bone and Mineral Research |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2010 |
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Keywords
- Aging
- Bone repair
- Cytokine
- TNF
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine
Cite this
Restoration of regenerative osteoblastogenesis in aged mice : Modulation of TNF. / 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.
In: Journal of Bone and Mineral Research, Vol. 25, No. 1, 01.01.2010, p. 114-123.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Restoration of regenerative osteoblastogenesis in aged mice
T2 - Modulation of TNF
AU - Wahl, Elizabeth C.
AU - Aronson, James
AU - Liu, Lichu
AU - Fowlkes, John L.
AU - Thrailkill, Kathryn M.
AU - Bunn, Robert C.
AU - Skinner, Robert A.
AU - Miller, Mike J.
AU - Cockrell, Gael E.
AU - Clark, Lindsey M.
AU - Ou, Yang
AU - Isales, Carlos M
AU - Badger, Thomas M.
AU - Ronis, Martin J.
AU - Sims, John
AU - Lumpkin, Charles K.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
KW - Aging
KW - Bone repair
KW - Cytokine
KW - TNF
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UR - http://www.scopus.com/inward/citedby.url?scp=77953402288&partnerID=8YFLogxK
U2 - 10.1359/jbmr.090708
DO - 10.1359/jbmr.090708
M3 - Article
VL - 25
SP - 114
EP - 123
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 1
ER -