Mice lacking the type I interleukin-1 receptor do not lose bone mass after ovariectomy.
We measured the effects of ovariectomy on the bone mass of mice that lacked type I interleukin-1 receptor (IL-I R1 -/- mice) in two genetic backgrounds (C57BL/6 x 129/Sv and C57BL/6) to investigate the role of interleukin-1 in the actions of estrogen on bone. At three weeks after surgery, ovariectomized wild-type mice decreased trabecular bone volume in the proximal humerus by 70% in a C57BL/6 x 129/Sv background and 48% in a C57BL/6 background compared to sham-operated controls. In contrast, there was no significant decrease in trabecular bone mass in IL-1 R1 -/- mice after ovariectomy. The estrogen status of all groups was confirmed by measurement of uterine wet weight. These results demonstrate that a functional IL-1 response pathway is required for mice to lose trabecular bone mass after ovariectomy in this model and they imply that IL-1 is an important mediator of the effects of ovariectomy on bone mass. Hence, therapeutic interventions that block the effects of IL-1 on bone may be beneficial for treating diseases of rapid bone loss such as post-menopausal osteoporosis.
Lorenzo
J A
JA
VA Connecticut Healthcare System, Newington 06111, USA. jlorenzo@nso2.uchc.edu
Naprta
A
A
Rao
Y
Y
Alander
C
C
Glaccum
M
M
Widmer
M
M
Gronowicz
G
G
Kalinowski
J
J
Pilbeam
C C
CC
D000818:Animals; D015519:Bone Density; D005260:Female; D006811:Humerus / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics*; D009929:Organ Size; D010052:Ovariectomy; D011184:Postoperative Period; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D012016:Reference Values; D014599:Uterus / Q000033:anatomy & histology
D017472:Receptors, Interleukin-1