R. Hatton et al., ANGIOTENSIN-II IS GENERATED FROM ANGIOTENSIN-I BY BONE-CELLS AND STIMULATES OSTEOCLASTIC BONE-RESORPTION IN-VITRO, Journal of Endocrinology, 152(1), 1997, pp. 5-10
During bone resorption, osteoclasts are closely associated with endoth
elial cells. The latter are able to produce several agents that regula
te bone resorption. In view of the increasing evidence that angiotensi
n II, which can be generated by endothelial cells, has actions outside
the traditional renin-angiotensin system, we tested the effect of ang
iotensin II on bone resorption. Angiotensin II showed no effect either
on osteoclast formation or on bone resorption by isolated osteoclasts
. However, in co-cultures of osteoclasts with calvarial or MC3T3-E1 os
teoblastic cells, and in osteoclastic cultures co-cultured with other
bone cells obtained by prolonged sedimentation, angiotensin II stimula
ted bone resorption to a similar degree to that observed with 1,25(OH)
(2) vitamin D-3. Stimulation of resorption was noted at concentrations
of 10(-7) M and above. We found that angiotensin I also stimulated bo
ne resorption in co-cultures of osteoclasts with osteoblastic cells, a
nd that this action was inhibited by inhibitors of angiotensin-convert
ing enzyme. These results identify angiotensin I and II as potent stim
ulators of osteoclastic bone resorption, and raise the possibility tha
t bone might contain a tissue-renin-angiotensin system that might play
a role in the regulation of bone resorption.