Expression of DKK1 in gallus of distraction gap during mandibular distraction osteogenesis and its implication

Abstract

Objective To investigate the expression of Wnt/β-catenin signal antagonist DKK1 protein in callus of distraction gap during mandibular distraction osteogenesis (MDO). Methods Twenty four healthy New Zealand rabbits were randomly divided into distraction group, fracture control group, with twelve rabbits each, respectively. In distraction group, bilateral mandibular distraction models were established. In control group, after bilateral mandibular osteotomy, the two bone fragments were fixed by titanium plate and screws with a 5 mm gap. The expression of DKK1 in the distracted calluses was analyzed by cell digital imaging software. Results Expression of DKK1 was co-localized in the nucleus and cytoplasm of osteoblasts, fibroblasts, cartilageand newly embedded osteocytes. The expression of DKK1 increased following distraction activated after surgery, peaked at 10 days after surgery, the population of cells that stained for DKK1 decreased gradually. At 31 to 38 days postoperatively, DKK1 expression reduced gradually, mainly located in the osteocyte, and both nucleus and cytoplasm were positive staining. At each time point, the expression of DKK1 in distraction group was higher than that in the control group and the difference was statistically significant (P<0.05). Conclusions During MDO, the Wnt/β-catenin pathway is activated due to the distraction and mechanical strain on the bone. With the increased expression of Wnt-related factors, the endogenous negative feedback is enhanced to induce DKK1 expression and to regulate the activated Wnt/β-catenin pathway. This would be beneficial to the new bone formation and remodeling in the distraction gap. Key words: Rabbits; Mandible; Distraction osteogenesis; Wnt signaling pathway; DKK1 protein