TY - JOUR
T1 - Restrain of bone growth by Estrogen-Mimetic Peptide-1 (EMP-1)
T2 - A micro-computed tomographic study
AU - Kasher, Roni
AU - Bajayo, Alon
AU - Gabet, Yankel
AU - Nevo, Nava
AU - Fridkin, Mati
AU - Katchalski-Katzir, Ephraim
AU - Kohen, Fortune
AU - Bab, Itai
N1 - Funding Information:
We are grateful to Batya Gayer and to Tikva Kulik (Weizmann Institute of Science, Israel) for technical assistance, to Aviva Kapitkovsky and Sara Rubinraut (Weizmann Institute of Science) for assistance in peptide synthesis, and to Yeda (Weizmann Institute of Science) for financial support.
PY - 2009/6/1
Y1 - 2009/6/1
N2 - 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 (μCT). 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 μCT 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.
AB - 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 (μCT). 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 μCT 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.
KW - Bone growth
KW - Estrogen-Mimetic Peptide
KW - Estrogenic activity
KW - Micro-computed tomography
UR - http://www.scopus.com/inward/record.url?scp=67349201058&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2009.02.019
DO - 10.1016/j.peptides.2009.02.019
M3 - Article
AN - SCOPUS:67349201058
SN - 0196-9781
VL - 30
SP - 1181
EP - 1186
JO - Peptides
JF - Peptides
IS - 6
ER -