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Early effects of parathyroid hormone on vascularized bone regeneration and implant osseointegration in aged rats
Biomaterials ( IF 12.8 ) Pub Date : 2018-06-26 , DOI: 10.1016/j.biomaterials.2018.06.035
Liting Jiang , Wenjie Zhang , Li Wei , Qi Zhou , Guangzheng Yang , Niandong Qian , Yun Tang , Yiming Gao , Xinquan Jiang

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 μg/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.



中文翻译:

甲状旁腺激素对老年大鼠血管骨再生和植入骨整合的早期影响

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)是用于治疗骨质疏松症的合成代谢药物。然而,关于其在衰老中对血管化骨再生和植入物骨整合的作用和机制知之甚少。在当前的研究中,我们采用体内和体外方法探讨PTH(1-34)对血管生成和成骨微环境的早期作用机制,以增强老年大鼠的植入物骨整合。从植入第二天开始,对20个月大的雌性大鼠每天皮下注射30μg/ kg PTH(1-34),持续5周。放射学和组织学分析证实,PTH(1-34)改善了新骨的形成,老年大鼠早期的血管生成和植入物骨整合。老年骨间充质干细胞(BMSCs)的成骨潜力增加,而其成脂能力减弱。此外,PTH(1–34)被证明可通过体外内皮细胞迁移和血管形成直接促进血管生成。同时,PTH(1–34)通过分泌血管生成和成骨生长因子来诱导早期血管形成并间接刺激BMSC的迁移或分化,从而刺激更多的破骨细胞参与骨重塑。在一起,这些结果表明了对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骼重塑和新骨形成的机制的洞察力,

更新日期:2018-06-27
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