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

46 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 1 2010

Fingerprint

Keywords

Aging
Bone repair
Cytokine
TNF

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Orthopedics and Sports Medicine

Cite this

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

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

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

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. / Restoration of regenerative osteoblastogenesis in aged mice : Modulation of TNF. In: Journal of Bone and Mineral Research. 2010 ; Vol. 25, No. 1. pp. 114-123.

@article{86675771d0e74c44a0b635d8cec20cd9,

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 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,

day = "1",

doi = "10.1359/jbmr.090708",

language = "English (US)",

volume = "25",

pages = "114--123",

journal = "Journal of Bone and Mineral Research",

issn = "0884-0431",

publisher = "Wiley-Blackwell",

number = "1",

}

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

UR - http://www.scopus.com/inward/record.url?scp=77953402288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953402288&partnerID=8YFLogxK

U2 - 10.1359/jbmr.090708

DO - 10.1359/jbmr.090708

M3 - Article

C2 - 19580462

AN - SCOPUS:77953402288

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 -

Access to Document

10.1359/jbmr.090708