Parathyroid Hormone Derivative with Reduced Osteoclastic Activity Promoted Bone Regeneration via Synergistic Bone Remodeling and Angiogenesis.
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2020
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Abstract
Osteogenesis, osteoclastogenesis, and angiogenesis are the most important processes in bone repair. Parathyroid hormone (PTH) has pro-osteogenic, pro-osteoclastogenic, and proangiogenic effects and may be a candidate for use in bone defect repair. However, the local application of PTH to bone defects is counterproductive due to its excessive osteoclastic and bone resorptive effects. In this study, a PTH derivative, PTHrP-2, is developed that can be applied to local bone defects. First, a modified peptide with a calcium-binding repeat glutamine tail undergoes controlled local release from a ceramic material and is shown to be a better fit for the repair process than the unmodified peptide. Second, the modified peptide is shown to have strong pro-osteogenic activity due to mineralization and its facilitation of serine (Ser) phosphorylation. Third, the modified peptide is shown to maintain the pro-osteoclastogenic and proangiogenic properties of the unmodified peptide, but its pro-osteoclastogenic activity is reduced compared to that of the unmodified peptide. The reduced pro-osteoclastogenic and increased pro-osteogenic properties of the modified peptide reverse the imbalance between osteoblasts and osteoclasts with local PTH application and shift bone resorption to bone regeneration.
| Reference Key |
huang2020parathyroidsmall
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|---|---|
| Authors | Huang, Jinghuan;Lin, Dan;Wei, Zhanying;Li, Qi;Zheng, Jin;Zheng, Qixin;Cai, Lin;Li, Xiaolin;Yuan, Yuan;Li, Jingfeng; |
| Journal | Small (Weinheim an der Bergstrasse, Germany) |
| Year | 2020 |
| DOI |
10.1002/smll.201905876
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