Nasal administration of a novel recombinant human parathyroid hormone (1–34) analog for the treatment of osteoporosis of ovariectomized rats

Add time:09/03/2019    Source:sciencedirect.com

Synthetic human parathyroid (1–34) (hPTH (1–34)) is known to have the full biological activity of the holohormone for osteoporosis. This study is about designing a novel analog of hPTH (1–34) which is more suitable for intranasal administration. We likewise evaluate effectiveness of the nasal drops against osteoroporosis. Through fusion expression of combining gene, cell disruption, inclusion body washing, ethanol fraction precipitation, acid hydrolysis, and CM-52 ion exchange column chromatography Pro-Pro-[Arg11] hPTH (1–34)-Pro-Pro was designed and produced. Nasal drops of Pro-Pro-[Arg11] hPTH (1–34)-Pro-Pro were prepared and administrated to ovariectomized rats. After 12 weeks of raising, Bone Material Densities (BMD) of vertebrae were examined by Dual Energy X-Ray Absorptiometry (DEXA). The average BMD of these groups treated with nasal drops of the peptide were 28.0%–47.2% (P < 0.01) higher than that of the group treated with normal saline (NS). The subchondral bone plates of the femoral heads were examined by scanning electron microscopy and a defined planar section was photographed. Percentage of the area of the cancellous bone was calculated. Percentages of the groups treated with nasal drops of the peptide increased; values were significantly different to that of the group treated with NS (P < 0.001) and were even equivalent to that of normal groups. These results show that nasal drops of Pro-Pro-[Arg11] hPTH (1–34)-Pro-Pro are effective against osteoporosis.

► 4PPTH is expressed in the form of a fusion protein. ► N-terminal and C-terminal Pro-Pro extension of Pro-Pro-[Arg11] hPTH (1–34)-Pro-Pro were added to protect against hydrolyzation by some proteases. ► N-terminal Pro-Pro can be set free to perform its bioactivity by DPPIV in serum. ► The substitution (Leu (11) → Arg) makes 4PPTH more potent.

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