期刊
SMALL
卷 16, 期 6, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201905876
关键词
angiogenesis; bone remodeling; controlled release; parathyroid hormone related peptide; synergistic effects
类别
资金
- National Natural Science Foundation of China [81871752, 81301538, 81572178]
- High-level Personnel Program of Wuhan University [600400002]
- Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund [cxpy2016035]
- Scientific Research Project of Shanghai Municipal Commission of Health and Family Planning [1814090400, 20164Y0062]
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.
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