The effect of nicotine on gene expression during spine fusion.
METHODS
A rabbit model of posterolateral spine fusion was used to investigate the effect of nicotine on cytokine expression during spine fusion.


OBJECTIVE
To determine the effects of nicotine on the known gene expression pattern of bone morphogens and related proteins expressed during spine fusion.


BACKGROUND
The mechanism by which nicotine increases the pseudarthrosis rate of spine fusion is unknown. Recently, a distinct temporal and spatial pattern of cytokine expression during bone formation has been described. The authors hypothesized that nicotine would alter this known pattern, thereby revealing the mechanism by which nicotine exerts its effect.


METHODS
Twenty-eight New Zealand White rabbits underwent posterolateral spine fusion with autogenous bone graft. Fourteen rabbits received systemic nicotine by a miniosmotic pump. Fusions were harvested at 0, 2, 5, and 7 days and 2, 3, and 4 weeks after arthrodesis. Specimens were divided into the outer zones adjacent to the transverse processes and the central zones between the transverse processes. Gene expression of type I and II collagen, bone morphogenic protein-2, -4, and -6 and basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) was then measured at each time point in each of the two zones.


RESULTS
Nicotine inhibited expression of all cytokines measured, mainly in the central zone. However, the previously described temporal and spatial patterns of expression were preserved.


CONCLUSIONS
Nicotine inhibits expression of a wide range of cytokines, including those associated with neovascularization and osteoblast differentiation. Therefore, the effects of nicotine appear to involve more than just local vasoconstriction.
Theiss
S M
SM
Division of Orthopedic Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. Steven.Theiss@ortho.uab.edu
Boden
S D
SD
Hair
G
G
Titus
L
L
Morone
M A
MA
Ugbo
J
J
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016025:Bone Transplantation / Q000009:adverse effects*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008222:Lymphokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009538:Nicotine / Q000009:adverse effects*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D011183:Postoperative Complications / Q000139:chemically induced*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D012907:Smoking / Q000009:adverse effects*; D013123:Spinal Fusion / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014945:Wound Healing / Q000187:drug effects*
D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009538:Nicotine; D003094:Collagen