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 (> or = 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.
Pietschmann
P
P
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
Farsoudi
K H
KH
Hoffmann
O
O
Klaushofer
K
K
Hörandner
H
H
Peterlik
M
M
D000682:Amyloid / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption / Q000188:drug therapy*; D058228:Islet Amyloid Polypeptide; D051379:Mice; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013268:Stimulation, Chemical
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D010281:Parathyroid Hormone