Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China.
Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Mol Med Rep. 2017 Dec;16(6):8923-8929. doi: 10.3892/mmr.2017.7693. Epub 2017 Oct 3.
Chronic periodontitis, a common oral disease, usually results in irreversible bone resorption. Bone regeneration is a complex process between bone‑forming activity of osteoblasts and bone‑resorbing activity of osteoclasts, and still remains a challenge for physicians clinically. A previous study demonstrated that the mechanistic target of rapamycin signaling pathway is involved in osteogenic differentiation of mesenchymal stromal cells. Herein, whether rapamycin could be used to induce osteogenic differentiation of primary bone marrow‑derived mesenchymal stem cells (BMSCs) in vitro and promote new bone formation in vivo were evaluated. The results demonstrated that rapamycin alone was not enough to fully induce osteoblast differentiation in vitro and enhanced bone regeneration in vivo. Interestingly, rapamycin in rapamycin plus lipopolysaccharide (LPS)‑treated BMSCs significantly increased the gene expression levels of Sp7 transcription factor, runt related transcription factor 2, alkaline phosphatase (ALP) and collagen I (Col I), ALP activity, and calcium nodule at different time points in vitro, indicating that osteoblast differentiation occurs by rapamycin when BMSCs are exposed to LPS simultaneously. It was also demonstrated that rapamycin in rapamycin plus LPS‑treated rats promoted bone regeneration in vivo. These results suggest that rapamycin may influence osteoblast differentiation and new bone formation after LPS induces an inflammatory environment. Rapamycin may be used to treat periodontitis associated with bone loss in future clinical practice.
慢性牙周炎是一种常见的口腔疾病,通常导致不可逆转的骨质吸收。骨再生是成骨细胞骨形成活性和破骨细胞骨吸收活性之间的复杂过程,临床上仍然是一个挑战。先前的研究表明,雷帕霉素靶蛋白信号通路参与间充质基质细胞的成骨分化。在此,评估雷帕霉素是否可用于体外诱导原代骨髓间充质干细胞(BMSCs)的成骨分化,并促进体内新骨形成。结果表明,雷帕霉素单独使用不足以完全诱导体外成骨分化并增强体内骨再生。有趣的是,雷帕霉素加脂多糖(LPS)处理的 BMSCs 中的雷帕霉素显著增加了 Sp7 转录因子、 runt 相关转录因子 2、碱性磷酸酶(ALP)和胶原蛋白 I(Col I)、ALP 活性和钙结节的基因表达水平在体外的不同时间点,表明当 BMSCs 同时暴露于 LPS 时,雷帕霉素会引发成骨细胞分化。还表明,雷帕霉素加 LPS 处理的大鼠体内的雷帕霉素促进了骨再生。这些结果表明,雷帕霉素可能会影响 LPS 诱导炎症环境后成骨细胞分化和新骨形成。雷帕霉素将来可能用于治疗与骨丢失相关的牙周炎。