Increased Runx2 expression associated with enhanced Wnt signaling in PDLLA internal fixation for fracture treatment

Abstract

Abstract. Poly-D-L lactide (PDLLA) biodegradable implants to heal fractures are widely applied in orthopedic surgeries. However, whether the process of fracture healing is regulated differently when PDLLA is used compared with traditional metal materials remains unclear. Runt-related transcription factor 2 (Runx2) and canonical Wnt signaling are essential and may interact reciprocally in the regulation of osteogenesis during bone repair. In the present study, a rat femoral open osteotomy model was used to compare the curative efficacy of a PDLLA rod and Kirschner wire under intramedullary fixation for fracture treatment. The dynamic expression of Runx2 and key components of the canonical Wnt signaling in callus tissue during fracture healing was also investigated. The results of the current study indicate that at weeks 4 and 6 following fixation, the callus bone structural parameters of microCT were significantly improved by PDLLA rod compared to that of Kirschner wire. In addition, at weeks 4 and 6 after fixation, the protein and mRNA expression of Runx2 and the positive regulators of canonical Wnt signaling, such as Wnts and β-catenin, were significantly increased. However, the protein and mRNA expression levels of the negative regulators of canonical Wnt signaling, such as glycogen synthase kinase-3β, were significantly decreased in callus tissue when treated with PDLLA rod compared with Kirschner wire. Collectively, these data indicate that compared to the traditional metal material, using PDLLA internal fixation for fracture treatment may further improve bone formation, which is associated with the increased expression of Runx2 and the enhancement of canonical Wnt signaling. IntroductionSince the use of biodegradable implants to heal fractures by Rokkanen et al in 1985, the method of using biodegradable materials has been widely applied in orthopedic surgeries (1-3). Biodegradable materials exhibit various advantages in the treatment of fractures compared with the use of traditional metal implants, including the elimination of implant removal, reduction of the 'stress shielding' effect, improvement of biocompatibility, reduction of radiological artifacts and utilization of magnetic resonance imaging assessment following surgery (4,5). Poly-D-L lactide (PDLLA) is a material with an intermediate degradation time (PDLLA begins to degrade at ~12 weeks) and may be completely replaced by bone tissue following surgery, thus, it is considered to be one of the most effective biodegradable materials for the treatment of fractures (6-8). However, with the exception of clinical outcomes, the differences in the biological processes following the use of PDLLA and metal fixation to treat a fracture remain unknown.The fracture healing process has been widely accepted to comprise a series of overlapping phases; these include inflammation, repair and remodeling events (9). This multistage repair process involves a variety of complex and well-orchestrated cellular and molecular processes, and should be considered as a special...

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