The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou, China.
FEBS Open Bio. 2020 Aug;10(8):1503-1515. doi: 10.1002/2211-5463.12906. Epub 2020 Jun 29.
Large-volume bone defects can result from congenital malformation, trauma, infection, inflammation and cancer. At present, it remains challenging to treat these bone defects with clinically available interventions. Allografts, xenografts and most synthetic materials have no intrinsic osteoinductivity, and so an alternative approach is to functionalize the biomaterial with osteoinductive agents, such as bone morphogenetic protein 2 (BMP2). Because it has been previously demonstrated that human salivary histatin-1 (Hst1) promotes endothelial cell adhesion, migration and angiogenesis, we examine here whether Hst1 can promote BMP2-induced bone regeneration. Rats were given subcutaneous implants of absorbable collagen sponge membranes seeded with 0, 50, 200 or 500 μg Hst1 per sample and 0 or 2 μg BMP2 per sample. At 18 days postsurgery, rats were sacrificed, and implanted regional tissue was removed for micro computed tomography (microCT) analyses of new bone (bone volume, trabecular number and trabecular separation). Four samples per group were decalcified and subjected to immunohistochemical staining to analyze osteogenic and angiogenic markers. We observed that Hst1 increased BMP2-induced new bone formation in a dose-dependent manner. Co-administration of 500 μg Hst1 and BMP2 resulted in the highest observed bone volume and trabecular number, the lowest trabecular separation and the highest expression of osteogenic markers and angiogenic markers. Our results suggest that coadministration of Hst1 may enhance BMP2-induced osteogenesis and angiogenesis, and thus may have potential for development into a treatment for large-volume bone defects.
大体积骨缺损可由先天畸形、创伤、感染、炎症和癌症引起。目前，临床上可用的干预措施仍然难以治疗这些骨缺损。同种异体移植物、异种移植物和大多数合成材料没有内在的成骨诱导性，因此替代方法是用成骨诱导剂对生物材料进行功能化，例如骨形态发生蛋白 2 (BMP2)。因为先前已经证明人类唾液组蛋白-1 (Hst1) 促进内皮细胞黏附、迁移和血管生成，所以我们在这里检查 Hst1 是否可以促进 BMP2 诱导的骨再生。给大鼠皮下植入可吸收胶原海绵膜，每个样本中种植 0、50、200 或 500μg 的 Hst1 和 0 或 2μg 的 BMP2。手术后 18 天，处死大鼠，取出植入区域组织，进行微计算机断层扫描 (microCT) 分析新骨（骨体积、小梁数和小梁分离）。每组 4 个样本脱钙，进行免疫组织化学染色，分析成骨和血管生成标志物。我们观察到 Hst1 以剂量依赖的方式增加 BMP2 诱导的新骨形成。联合使用 500μg Hst1 和 BMP2 可导致观察到的骨体积和小梁数最高、小梁分离最低以及成骨标志物和血管生成标志物表达最高。我们的结果表明，联合使用 Hst1 可能增强 BMP2 诱导的成骨和血管生成，因此可能有潜力开发成为治疗大体积骨缺损的方法。
