The role of antimiR-26a-5p/biphasic calcium phosphate in repairing rat femoral defects

AntimiR-26a-5p/双相磷酸钙修复大鼠股骨缺损的作用

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作者:Xiaoyan Yuan, Lu Han, Hai Lin, Zeyou Guo, Yanling Huang, Shasha Li, Ting Long, Wei Tang, Weidong Tian, Jie Long

Abstract

Although miRNAs have been implicated in the osteogenic differentiation of stem cells, their role in bone repair and reconstruction in tissue‑engineered bone grafts remains unclear. We previously reported that microRNA (miR)‑26a‑5p inhibited the osteogenic differentiation of adipose‑derived mesenchymal stem cells (ADSCs), and that antimiR‑26a‑5p exerted the opposite effect. In the present study, the role of miR‑26a‑5p‑ and antimiR‑26a‑5p‑modified ADSCs combined with biphasic calcium phosphate (BCP) scaffolds was evaluated in a rat femur defect model. The aim of the present study was to improve the understanding of the role of miR‑26a‑5p in bone regeneration in vivo, as well as to provide a new method to optimize the osteogenic ability of BCPs. ADSCs were infected with Lv‑miR‑26a‑5p, Lv‑miR‑NC, Lv‑antimiR‑26a‑5p or Lv‑antimiR‑NC respectively, and then combined with BCP scaffolds to repair rat femoral defects. Using X‑rays, micro‑computed tomography and histology at 2, 4, and 8 weeks postoperatively, the quantity and rate of bone regeneration were analyzed, revealing that they were the highest in animals treated with antimiR‑26a‑5p and the lowest in the miR‑26a‑5p treatment group. The expression levels of osteocalcin, collagen I, Runt‑related transcription factor 2, Wnt family member 5A and calmodulin‑dependent protein kinase II proteins were positively correlated with the bone formation rate. Taken together, the present results demonstrated that miR‑26a‑5p inhibited bone formation while antimiR‑26a‑5p accelerated bone formation via the Wnt/Ca2+ signaling pathway. Therefore, antimiR‑26a‑5p‑modified ADSCs combined with BCP scaffolds may be used to construct an effective tissue‑engineering bone graft for bone repair and reconstruction.

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