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

doi:10.1359/jbmr.090708

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

Endocrinology

Research output: Contribution to journal › Article › peer-review

50 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 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	https://doi.org/10.1359/jbmr.090708
State	Published - Jan 2010

Keywords

Aging
Bone repair
Cytokine
TNF

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Orthopedics and Sports Medicine

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10.1359/jbmr.090708

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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

Wahl, EC, Aronson, J, Liu, L, Fowlkes, JL, Thrailkill, KM, Bunn, RC, Skinner, RA, Miller, MJ, Cockrell, GE, Clark, LM, Ou, Y, Isales, CM, Badger, TM, Ronis, MJ, Sims, J & Lumpkin, CK 2010, 'Restoration of regenerative osteoblastogenesis in aged mice: Modulation of TNF', Journal of Bone and Mineral Research, vol. 25, no. 1, pp. 114-123. https://doi.org/10.1359/jbmr.090708

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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.",

keywords = "Aging, Bone repair, Cytokine, TNF",

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

year = "2010",

month = jan,

doi = "10.1359/jbmr.090708",

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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.

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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.

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KW - Bone repair

KW - Cytokine

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Restoration of regenerative osteoblastogenesis in aged mice: Modulation of TNF

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