ADRENOMEDULLIN IS A POTENT STIMULATOR OF OSTEOBLASTIC ACTIVITY IN-VITRO AND IN-VIVO

Adrenomedullin is a 52-amino acid vasodilator peptide produced in many tissues, including bone. It has 20% sequence identity with amylin, a regulator of osteoblast growth, and circulates in picomolar concentrat ions. The present study assesses whether adrenomedullin also acts on o steoblasts. At concentrations of 10(-12) M and greater, adrenomedullin produced a dose-dependent increase in cell number and [H-3]thymidine incorporation in cultures of fetal rat osteoblasts. This effect was al so seen with adrenomedullin-(15-52), -(22-52), and -(27-52), but adren omedullin-(40-52) was inactive. These effects were lost in the presenc e of amylin blockers, suggesting they were mediated by the amylin rece ptor. Adrenomedullin also increased [H-3]thymidine incorporation into cultured neonatal mouse calvaria but, unlike amylin, did not reduce bo ne resorption in this model. Adrenomedullin stimulated phenylalanine i ncorporation into both isolated osteoblasts and calvaria. When injecte d daily for 5 days over the calvariae of adult mice, it increased inde xes of bone formation two- to threefold (P < 0.0001) and increased min eralized bone area by 14% (P = 0.004). It is concluded that adrenomedu llin regulates osteoblast function and that it increases bone mass in vivo. The potential of this family of peptides in the therapy of osteo porosis should be further evaluated.