ANGIOTENSIN-II IS GENERATED FROM ANGIOTENSIN-I BY BONE-CELLS AND STIMULATES OSTEOCLASTIC BONE-RESORPTION IN-VITRO

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.