Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cytotherapy. 2023 Sep;25(9):946-955. doi: 10.1016/j.jcyt.2023.05.013. Epub 2023 Jun 24.
While distraction osteogenesis (DO) achieves substantial bone regeneration, prolonged fixation may lead to infections. Existing stem cell and physical therapies have limitations, requiring the development of novel therapeutic approaches. Here, we evaluated high-mobility group box 1 (HMGB1) as a novel therapeutic target for DO treatment.
Micro-computed tomography (Micro-CT) analysis and histological staining of samples obtained from tibial DO model mice was performed. Transwell migration, wound healing, and proliferation assays were also performed on cultured human mesenchymal stem cells (hMSCs) and human umbilival vein endothelial cells (HUVECs). Tube formation assay was performed on HUVECs, whereas osteogenic differentiation assay was performed on hMSCs.
Micro-CT analysis and histological staining of mouse samples revealed that HMGB1 promotes bone regeneration during DO via the recruitment of PDGFRα and Sca-1 positve (PαS) cells and endothelial progenitor cells. Furthermore, HMGB1 accelerated angiogenesis during DO, promoted the migration and osteogenic differentiation of hMSCs as well as the proliferation, migration and angiogenesis of HUVECs in vitro.
Our findings suggest that HMGB1 has a positive influence on endogenous stem/progenitor cells, representing a novel therapeutic target for the acceleration of DO-driven bone regeneration.
虽然分散式骨生成（DO）可实现大量骨再生，但长时间固定可能会导致感染。现有的干细胞和物理疗法存在局限性，需要开发新的治疗方法。在这里，我们评估了高迁移率族蛋白 B1（HMGB1）作为 DO 治疗的新治疗靶点。
对胫骨 DO 模型小鼠的样本进行微计算机断层扫描（Micro-CT）分析和组织学染色。还对培养的人间充质干细胞（hMSC）和人脐静脉内皮细胞（HUVEC）进行了 Transwell 迁移、伤口愈合和增殖测定。对 HUVEC 进行了管形成测定，而对 hMSC 进行了成骨分化测定。
对小鼠样本的 Micro-CT 分析和组织学染色表明，HMGB1 通过募集血小板衍生生长因子受体α（PDGFRα）和 Sca-1 阳性（PαS）细胞和内皮祖细胞促进 DO 期间的骨再生。此外，HMGB1 在 DO 过程中加速了血管生成，促进了 hMSC 的迁移和成骨分化，以及 HUVEC 的增殖、迁移和血管生成。
我们的研究结果表明，HMGB1 对内源性干细胞/祖细胞有积极影响，是加速 DO 驱动的骨再生的新治疗靶点。
