Critical Reviews™ in Eukaryotic Gene Expression

ISSN for PRINT: 1045-4403

For Online Access

Best Paper Award Selection - Editorial Board Site

2003, Volume13

Issue 2-4

227 pages

DOI: 10.1615/CritRevEukaryotGeneExpr.v13.i24

Issue price - $507.00

Gary B. Schneider
, Associate Dean for Basic Medical Sciences and Research, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, P.O. Box 95, Rootstown, OH 44272-0095

Kristina J. Grecco
Division of Basic Medical Sciences, Northeastern Ohio Universities College of Medicine, Rootstown, OH

Fayez F. Safadi
Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140

Steven N. Popoff, Ph.D.
Professor and Chair of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140

Vitamin D-binding protein-macrophage activating factor (DBP-MAF) has previously been shown to stimulate bone resorption and correct the skeletal defects associated with osteopetrosis in two nonallelic mutations in rats. This same protein and a small fragment of the protein have now been shown to demonstrate an anabolic effect on the skeleton of both newborn and young adult, intact rats. The novel peptide fragment was synthetically produced based on the human amino acid sequence at the site of glycosylation in the third domain of the native protein (DBP). The peptide tested is 14 amino acids in length and demonstrates no homologies other than to that region of DBP. Newborn rats were injected i.p. with saline, peptide (0.4 ng/g body wt.) or DBP-MAF (2 ng/g body wt.) every other day from birth to 14 days of age. On day 16 the rats were euthanized and the long bones collected for bone densitometry by pQCT. After 2 weeks of treatment with either the whole protein (DBP-MAF) or the small peptide, bone density was significantly increased in the treated animals compared to the saline controls. Young adult female rats (180 grams) were given s.c. injections of saline or peptide (0.4 ng/g body wt. or 5 ng/g body wt.) every other day for 2 weeks; 2 days after the final injections, the rats were euthanized and the femurs and tibias collected for bone densitometry. Both doses of the peptide resulted in significant increases in bone density as determined by pQCT. Young adult rats were injected locally with a single dose of the peptide (1 mg) or saline into the marrow cavity of the distal femur. One week after the single injection, the bones were collected for radiographic and histological evaluation. The saline controls showed no evidence of new bone formation, whereas the peptide-treated animals demonstrated osteoinduction in the marrow cavity and osteogenesis of surrounding cortical and metaphyseal bone. These data suggest that DBP-MAF and the synthetic peptide represent therapeutic opportunities for the treatment of a number of bone diseases and skeletal disorders. Systemic administration could be used to treat osteoporosis and a number of other osteopenias, and local administration could be effective in fractures, bony defect repairs, spinal surgery, and joint replacement.

DOI: 10.1615/CritRevEukaryotGeneExpr.v13.i24.190 Download article, 8 pages

Article price - $35.00

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