microRNA-146a mediates distraction osteogenesis via bone mesenchymal stem cell inflammatory response.

Abstract

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.

• Authors: Huijuan Shen, Weidong Jiang, Yangyang Yu, Yuan Feng, Tao Zhang, Yan Liu, Lina Guo, Nuo Zhou, Xuanping Huang
• Journal: Acta histochemica (Acta Histochem) Vol. 124 Issue 6 Pg. 151913 (Aug 2022) ISSN: 1618-0372 [Electronic] Germany
• PMID: 35759812 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier GmbH. All rights reserved.

Chemical References

• Lipopolysaccharides
• MicroRNAs

Topics

• Animals
• Bone Marrow Cells
• Cell Differentiation
• Cells, Cultured
• Dogs
• Inflammation (metabolism)
• Lipopolysaccharides (pharmacology)
• Mesenchymal Stem Cells
• MicroRNAs (metabolism)
• Osteogenesis
• Osteogenesis, Distraction
• X-Ray Microtomography