Departement of Oral and Maxillofacial Surgery, College of Stomatology, Guangxi Medical University, Nanning 530021, People's Republic of China; Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, Guangxi Key Laboratory of Oral and Maxillofacial Surgery Disease Treatment, Guangxi Clinical Research Center for Craniofacial Deformity, Nanning 530021, People's Republic of China.
Departement of Oral and Maxillofacial Surgery, College of Stomatology, Guangxi Medical University, Nanning 530021, People's Republic of China; Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, Guangxi Key Laboratory of Oral and Maxillofacial Surgery Disease Treatment, Guangxi Clinical Research Center for Craniofacial Deformity, Nanning 530021, People's Republic of China.
Acta Histochem. 2022 Aug;124(6):151913. doi: 10.1016/j.acthis.2022.151913. Epub 2022 Jun 24.
Distraction osteogenesis (DO) is a widely used surgical technique to repair bone defects, partly owing to its high efficiency in inducing osteogenesis; however, the process of osteogenesis is complex, and the precise mechanism is still unclear. Among the factors identified for an effective DO procedure, well-controlled inflammation is essential. We aimed to explore how microRNA(miR)-146a, a negative regulator of inflammation, influences osteogenesis in DO. First, we established canine right mandibular DO and bone fracture models to evaluate the expression level of miR-146a in response to these procedures. Second, bone marrow mesenchymal stem cells (BMSCs) were isolated from healthy puppies and cultured with lipopolysaccharide (LPS) to observe how inflammation affects osteogenesis. Finally, the osteogenesis activity of BMSCs transfected with lentiviral vector either overexpressing (miR-146a-up) or inhibited for miR-146a expression was evaluated. miR-146a-up-transfected BMSCs were injected locally into the distraction gaps of the DO model canines. On days 42 and 56 post-surgery, the bone volume/tissue volume and bone mineral density values were evaluated via using micro-computed tomography, and newly formed tissues were harvested and evaluated via histological staining. The expression of miR-146a in both the DO canine model and LPS-stimulated BMSCs increased. Overexpression of miR-146a enhanced cell proliferation, migration, and osteogenic differentiation. Additionally, the newly formed callus was improved in canine mandibles injected with miR-146a-up-transfected BMSCs. In summary, miR-146a regulates mandibular DO by improving osteogenesis, and can serve as a potential target to shorten the therapy period of DO.
牵张成骨术（DO）是一种广泛应用于修复骨缺损的外科技术，部分原因在于其在诱导成骨方面的高效率；然而，成骨过程复杂，确切机制尚不清楚。在确定有效的 DO 程序的因素中，受控制的炎症是必不可少的。我们旨在探索负性炎症调节因子 microRNA(miR)-146a 如何影响 DO 中的成骨作用。首先，我们建立了犬右侧下颌骨 DO 和骨折模型，以评估 miR-146a 对这些程序的反应的表达水平。其次，我们从健康幼犬中分离骨髓间充质干细胞（BMSCs），并用脂多糖（LPS）培养，观察炎症如何影响成骨作用。最后，评估转染了过表达（miR-146a-up）或抑制 miR-146a 表达的慢病毒载体的 BMSCs 的成骨活性。将 miR-146a-up 转染的 BMSCs 局部注射到 DO 犬模型的牵张间隙中。术后第 42 天和第 56 天，通过 micro-CT 评估骨量/组织量和骨密度值，并采集新形成的组织进行组织学染色评估。DO 犬模型和 LPS 刺激的 BMSCs 中的 miR-146a 表达均增加。过表达 miR-146a 增强了细胞增殖、迁移和成骨分化。此外，注射 miR-146a-up 转染的 BMSCs 可改善犬下颌骨的新生骨痂。总之，miR-146a 通过改善成骨作用来调节下颌骨 DO，并可作为缩短 DO 治疗周期的潜在靶点。
