INHIBITORY EFFECT OF AMYLIN ON BASAL AND PARATHYROID-HORMONE STIMULATED BONE-RESORPTION IN CULTURED NEONATAL MOUSE CALVARIA

Amylin is a secretory product of pancreatic beta-cells which shares major sequence homology with calcitonin gene-related peptide. In neonatal mouse calvaria maintained in organ culture for 72 h, amylin inhibited basal (i.e., unstimulated) resorption in medium concentrations above 2.5 x 10(-9) M. In addition, amylin (greater-than-or-equal-to 1.0 x 10(-7) M) in a calcitonin-like fashion transiently inhibited bone resorption induced by 1.0 x 10(-8) M PTH (''escape phenomenon''). Pretreatment of calvarial bones with amylin (1.0 x 10(-8)-1.0 X 10(-6) M) for 72 h attenuated the subsequent response to 1.0 x 10(-8) M PTH. Changes in location and appearance of osteoclasts in amylin-treated bones, as visualized by light microscopy, suggest that amylin inhibits bone resorption by causing a loss of specialized contact zones to the mineralized matrix in resorbing osteoclasts, and in addition, by preventing retraction of osteoblasts from the mineralized surface which impedes attachment of osteoclasts thereon.