TY - JOUR
T1 - IL-6, LIF, and TNF-α regulation of GM-CSF inhibition of osteoclastogenesis in vitro
AU - Gorny, Genevieve
AU - Shaw, Aubie
AU - Oursler, Merry Jo
N1 - Funding Information:
We would like to acknowledge Drs. David Monroe and Thomas Spelsberg for assistance with the Real Time Polymerase Chain Reaction assays. This work was generously supported by a grant from the Department of Defense #DAMD17-00-1-0346, the Whiteside Institute for Clinical Research, National Institutes of Health grant #DE14680.
PY - 2004/3/10
Y1 - 2004/3/10
N2 - During pathological bone loss, factors that are both stimulatory and inhibitory for osteoclast differentiation are over-expressed. Despite the presence of inhibitory factors, osteoclast differentiation is significantly enhanced to bring about bone loss. To examine the hypothesis that stimulatory growth factors overcome the effects of inhibitory factors, we have examined the ability of IGF-I, IGF-II, IL-6, LIF, and TNF-α to overcome osteoclast differentiation inhibition by GM-CSF in vitro. Osteoclast numbers were significantly elevated by treatment with IGF-I, IGF-II, IL-6, LIF, or TNF-α alone whereas GM-CSF treatment of stromal cell and osteoclast co-cultures inhibited osteoclast formation. IL-6, LIF, or TNF-α, individually overcame GM-CSF inhibition whereas neither IGF-I nor IGF-II treatment overcame GM-CSF inhibition. Interestingly, GM-CSF addition with either IL-6 or TNF-α increased osteoclast numbers beyond that seen with either IL-6 or TNF-α alone. Combined treatment with TNF-α and IL-6 showed a significant increase in osteoclast numbers with GM-CSF addition. Examination of the impacts of these growth factors individually or in combinations on stromal cell M-CSF, RANKL, and OPG expression revealed a complex pattern involving alterations in the ratio of RANKL to OPG and/or M-CSF expression as candidate mechanisms of action.
AB - During pathological bone loss, factors that are both stimulatory and inhibitory for osteoclast differentiation are over-expressed. Despite the presence of inhibitory factors, osteoclast differentiation is significantly enhanced to bring about bone loss. To examine the hypothesis that stimulatory growth factors overcome the effects of inhibitory factors, we have examined the ability of IGF-I, IGF-II, IL-6, LIF, and TNF-α to overcome osteoclast differentiation inhibition by GM-CSF in vitro. Osteoclast numbers were significantly elevated by treatment with IGF-I, IGF-II, IL-6, LIF, or TNF-α alone whereas GM-CSF treatment of stromal cell and osteoclast co-cultures inhibited osteoclast formation. IL-6, LIF, or TNF-α, individually overcame GM-CSF inhibition whereas neither IGF-I nor IGF-II treatment overcame GM-CSF inhibition. Interestingly, GM-CSF addition with either IL-6 or TNF-α increased osteoclast numbers beyond that seen with either IL-6 or TNF-α alone. Combined treatment with TNF-α and IL-6 showed a significant increase in osteoclast numbers with GM-CSF addition. Examination of the impacts of these growth factors individually or in combinations on stromal cell M-CSF, RANKL, and OPG expression revealed a complex pattern involving alterations in the ratio of RANKL to OPG and/or M-CSF expression as candidate mechanisms of action.
KW - GM-CSF
KW - IGF-I
KW - IGF-II
KW - IL-6
KW - LIF
KW - Osteoclastogenesis
KW - TNF-α
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U2 - 10.1016/j.yexcr.2003.11.009
DO - 10.1016/j.yexcr.2003.11.009
M3 - Article
C2 - 14980510
AN - SCOPUS:1242339610
SN - 0014-4827
VL - 294
SP - 149
EP - 158
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -