کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2779981 1153288 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats
چکیده انگلیسی

Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac5c1, Aib3, Leu8, Gln10, Har11, Ala12, Trp14, Asp17]PTH(1-17)-NH2), a novel, chemically modified and cyclized hPTH(1-17) analog, that augments bone mass in ovariectomized, osteopenic rats. Subcutaneous administration of this structurally constrained, K13-D17 side-chain-to-side-chain cyclized peptide reversed bone loss and increased bone mineral density (BMD) up to or above baseline levels in rat long bones and vertebrae. Highly significant effects of ZP2307 were achieved at doses of 40–320 nmol/kg. Micro-CT and histomorphometric analyses showed that ZP2307 improved quantitative and qualitative parameters of bone structure. Biomechanical testing of rat femora confirmed that ZP2307 dramatically increased bone strength. Over a broad maximally effective dose range (40–160 nmol/kg) ZP2307 did not increase serum concentrations of ionized free calcium above normal levels. Only at the highest dose (320 nmol/kg) ZP2307 induced hypercalcemic calcium levels in the ovariectomized rats.To our knowledge ZP2307 is the smallest PTH peptide analog known to exert augmentation of bone. Our findings suggest that ZP2307 has the potential to effectively augment bone mass over a broad dose range without a concomitant increase in the serum concentration of ionized free calcium above the normal range.

Research highlights
► ZP2307, a new PTH analog that augments bone mass in ovariectomized, osteopenic rats.
► ZP2307 is the smallest PTH peptide analog known to exert augmentation of bone.
► Micro-CT and histomorphometric analyses showed that ZP2307 improved bone structure.
► ZP2307 had no effect on serum ionized free calcium at 40-160 nmol/kg.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 48, Issue 6, 1 June 2011, Pages 1319–1327
نویسندگان
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