Restrain of bone growth by estrogen-mimetic peptide-1 (EMP-1): a micro-computed tomographic study.
Estrogen has a key role in the regulation of skeletal growth and maintenance of bone mass. Recently, we developed peptides having estrogen-like activity as potential estrogen-based new drugs. The aim of the present study was to evaluate the influence of long-term administration of the most efficacious of these peptides, the hexapeptide EMP-1 (VSWFFE), on bone mass and development. EMP-1 was injected daily to ovariectomized (OVX) and intact young, sexually mature female mice for 10 weeks. Whole femora, including the cartilaginous growth plates were analyzed by micro-computed tomography (microCT). We found that peptide EMP-1 restrains bone growth in OVX mice: it inhibited dramatically bone longitudinal growth (40%), and decreased femoral diaphyseal diameter. Peptide EMP-1 had no effect on bone growth in normal mice, and did not influence the OVX-induced bone loss. We then developed a new microCT methodology to evaluate uncalcified and calcified growth plate parameters. In the OVX mice, peptide EMP-1 reduced volume and thickness of the uncalcified growth plate, a possible cause for the inhibition of bone longitudinal growth. Peptide EMP-1 may be used as a lead compound for the development of drugs to treat acromegalic patients.
Kasher
Roni
R
Department of Desalination and Water Treatment, Zuckerberg Institute for Water Research, The Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede-Boqer Campus 84990, Israel. kasher@bgu.ac.il
Bajayo
Alon
A
Gabet
Yankel
Y
Nevo
Nava
N
Fridkin
Mati
M
Katchalski-Katzir
Ephraim
E
Kohen
Fortune
F
Bab
Itai
I
D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000737:chemistry; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D010052:Ovariectomy; D055114:X-Ray Microtomography
D004967:Estrogens; D009842:Oligopeptides; C543187:valyl-seryl-tryptophyl-phenylalanyl-phenylalanyl-glutamic acid