Systemic administration of a novel octapeptide, amylin-(1---8), increases bone volume in male mice.
Amylin increases bone mass when administered systemically to mice. However, because of its size, the full peptide is not an ideal candidate for the therapy of osteoporosis. The fragment, amylin-(1---8), stimulates osteoblast proliferation in vitro, although it is without effect on carbohydrate metabolism. The present study assessed the effects of daily administration of this peptide on sexually mature male mice for 4 wk. Amylin-(1---8) almost doubled histomorphometric indices of osteoblast activity but did not change measures of bone resorption. Trabecular bone volume increased by 36% as a result of increases in both trabecular number and trabecular thickness, and tibial cortical width increased by 8%. On three-point bending tests of bone strength, displacement to fracture was increased by amylin-(1---8), from 0.302 +/- 0.013 to 0.351 +/- 0. 017 mm (P = 0.02). In a separate experiment using dynamic histomorphometry with bone-seeking fluorochrome labels, amylin-(1---8) was administered by local injection over the calvariae of female mice. Amylin-(1---8) (40 nM) increased the double-labeled surface threefold. The effect was dose dependent from 0.4 to 40 nM and was greater than that of an equimolar dose of human parathyroid hormone-(1---34) [hPTH-(1---34)]. Mineral apposition rate was increased by 40 nM amylin-(1---8) but not by hPTH-(1---34). Amylin-(1---8) thus has significant anabolic effects in vivo, suggesting that this peptide or analogs of it should be further evaluated as potential therapies for osteoporosis.
Cornish
J
J
Department of Medicine, University of Auckland, Auckland 1001, New Zealand. j.cornish@auckland.ac.nz
Callon
K E
KE
Gasser
J A
JA
Bava
U
U
Gardiner
E M
EM
Coy
D H
DH
Cooper
G J
GJ
Reid
I R
IR
D000682:Amyloid / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D007279:Injections, Subcutaneous; D058228:Islet Amyloid Polypeptide; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D012886:Skull / Q000187:drug effects; D019379:Teriparatide / Q000494:pharmacology; D013977:Tibia / Q000187:drug effects
D000682:Amyloid; D005456:Fluorescent Dyes; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D019379:Teriparatide