Pharmacological effects of a recombinant hPTH(1-34) derived peptide on ovariectomized rats.

A recombinant peptide Pro-Pro-[Arg(11)]hPTH(1-34)-Pro-Pro, was designed, biosynthesized, and purified in our lab (generated by substituting Arg for Leu at position 11 and adding -Pro-Pro to the carboxyl terminus of hPTH(1-34)-peptide), and reported to be capable of enhancing serum calcium level in chicken. In this investigation, we studied its impact on the structure, component, and biomechanical properties of rat bones. The pharmacological effect of Pro-Pro-[Arg(11)]hPTH(1-34)-Pro-Pro was investigated to evaluate its therapeutic potential for the treatment of osteoporosis, one of the most prevalent and rapidly spreading diseases in the world. 3-month-old normal female rats were sham-ovariectomized or ovariectomized, then fed for 14 weeks. Small doses of Pro-Pro-[Arg(11)]hPTH(1-34)-Pro-Pro were given to the rats afterward (daily subcutaneous injection of 0.4-0.9nmol/100g body weight for 16 weeks). Values of various parameters, including the body weight, the bone mass, the bone geometry, the bone biomechanics, the bone histology, the bone histomorphology, and the serum biochemistry, were collected before or after animal sacrifice. Daily subcutaneous injection of Pro-Pro-[Arg(11)]hPTH(1-34)-Pro-Pro induced 37.0-42.4% increase in vertebral BMD, 28.5-47.9% increase in femoral BMD, 30.7-43.7% decrease in marrow cavity or increase in trabecular bone area. The peptide also increased calcium, phosphorus, and collagen in bone by 52.1-59.7%, 24.5-34.7%, and 26.3-28.0%, respectively. In terms of mechanic properties, peptide administration elevated bone rigidity by 55.7-84.5%, decreased the deflection by 14.8-26.7%, and improved modulus of elasticity by 28.1-76.4%. These data suggest Pro-Pro-[Arg(11)]hPTH(1-34)-Pro-Pro has a positive effect on bone mass accumulation and microstructure improvement, fortifies bone strength, and possesses anti-aging capability, which may merit further investigation.