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 concentrations. The present study assesses whether adrenomedullin also acts on osteoblasts. At concentrations of 10(-12) M and greater, adrenomedullin produced a dose-dependent increase in cell number and [3H]thymidine incorporation in cultures of fetal rat osteoblasts. This effect was also seen with adrenomedullin-(15-52), -(22-52), and -(27-52), but adrenomedullin-(40-52) was inactive. These effects were lost in the presence of amylin blockers, suggesting they were mediated by the amylin receptor. Adrenomedullin also increased [3H]thymidine incorporation into cultured neonatal mouse calvaria but, unlike amylin, did not reduce bone resorption in this model. Adrenomedullin stimulated phenylalanine incorporation into both isolated osteoblasts and calvaria. When injected daily for 5 days over the calvariae of adult mice, it increased indexes of bone formation two- to threefold (P < 0.0001) and increased mineralized bone area by 14% (P = 0.004). It is concluded that adrenomedullin regulates osteoblast function and that it increases bone mass in vivo. The potential of this family of peptides in the therapy of osteoporosis should be further evaluated.
Cornish
J
J
Department of Medicine, University of Auckland, New Zealand.
Callon
K E
KE
Coy
D H
DH
Jiang
N Y
NY
Xiao
L
L
Cooper
G J
GJ
Reid
I R
IR
D053607:Adrenomedullin; D000682:Amyloid / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D012741:Sexual Maturation; D012886:Skull / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013936:Thymidine / Q000378:metabolism
D000682:Amyloid; D010446:Peptide Fragments; D010455:Peptides; C109255:amylin (8-37); D053607:Adrenomedullin; D013936:Thymidine