Early effects of parathyroid hormone on vascularized bone regeneration and implant osseointegration in aged rats
Early effects of parathyroid hormone on vascularized bone regeneration and implant osseointegration in aged rats
复制标题
甲状旁腺激素对老年大鼠血管化骨再生和种植体骨整合的早期影响
DOI：
10.1016/j.biomaterials.2018.06.035
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发表时间：
2018-10-01
期刊：
影响因子：
14
通讯作者：
Jiang, Xinquan
中科院分区：
文献类型：
--
作者：
Jiang, Liting;Zhang, Wenjie;Jiang, Xinquan
随着年龄的增长，骨量减少和成骨能力受损可能会影响牙种植体的结果。甲状旁腺激素（PTH）（1-34）是一种用于治疗骨质疏松症的合成代谢剂。然而，关于其在衰老过程中对血管化骨再生和种植体骨整合的作用和机制知之甚少。本研究采用体内和体外实验相结合的方法，探讨PTH（1-34）对老年大鼠种植体骨结合的早期作用机制。从植入的第二天开始，每天皮下注射30 μ g/kg PTH（1-34）给20月龄的雌性大鼠，持续5周。放射学和组织学分析证实，PTH（1-34）促进了老年大鼠早期新骨形成、血管生成和种植体骨结合。老年骨髓间充质干细胞（BMSCs）成骨能力增强，成脂能力减弱。此外，PTH（1-34）在体外显示直接通过内皮细胞迁移和血管形成促进血管生成。同时，PTH（1-34）刺激破骨细胞分泌促血管生成和成骨生长因子参与骨重建，诱导早期血管化，间接刺激BMSCs迁移或分化。总之，这些结果证明了对PTH（1-34）如何调节血管生成和成骨微环境以导致更活跃的骨重建和新骨形成的机理性见解，使其成为老年人群中快速血管化骨再生和植入物骨整合的优秀潜在治疗剂。(C)2018爱思唯尔有限公司版权所有。
The decreased bone mass and impaired osteogenesis capacities that occur with aging may influence the outcome of dental implants. Parathyroid hormone (PTH) (1-34) is an anabolic agent for the treatment of osteoporosis. However, little is known about its effects and mechanisms on vascularized bone regeneration and implant osseointegration in aging. In current study, we adopted both in vivo and in vitro approaches to explore the mechanisms of early actions of PTH (1-34) on the angiogenic and osteogenic microenvironment to enhance implant osseointegration in aged rats. Daily subcutaneous injections of 30 mu g/kg PTH (1-34) were given to female rats aged 20 months beginning on next day of implantation and lasting for 5 weeks. Radiological and histological analysis confirmed that PTH (1-34) improved new bone formation, angiogenesis and implant osseointegration in aged rats in the early stage. The osteogenic potential of aged bone mesenchymal stem cells (BMSCs) was enhanced, while their adipogenesis capacity was attenuated. Furthermore, PTH (1-34) was shown to promote angiogenesis directly via endothelial cell migration and blood vessel formation in vitro. Meanwhile, PTH (1-34) stimulated more osteoclasts participation in bone remodeling by secreting angiogenic and osteogenic growth factors to induce early vascularization and stimulate the migration or differentiation of BMSCs indirectly. Together, these results demonstrate mechanistic insight into how PTH (1-34) regulates the angiogenic and osteogenic microenvironment to result in more active bone remodeling and new bone formation, making it an excellent potential therapeutic agent for rapid vascularized bone regeneration and implant osseointegration in the aged population. (C) 2018 Elsevier Ltd. All rights reserved.