Recruitment of exogenous mesenchymal stem cells in mandibular distraction osteogenesis by the stromal cell-derived factor-1/chemokine receptor-4 pathway in rats.

Distraction osteogenesis is widely used in orthopaedic and craniofacial surgery. However, its exact mechanism is still poorly understood. The purpose of this study was to find out whether there is systemic recruitment of mesenchymal stem cells (MSC) to the neocallus in the distraction gap by the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis during osteogenesis. We examined the migration of MSC towards a gradient of SDF-1 in vitro. We also transplanted MSC labelled with green fluorescent protein (GFP) intravenously, with or without treatment with CXCR4-blocking antibody, into rats that had had unilateral mandibular distraction osteogenesis, and investigated the distribution of cells labelled with GFP in the soft callus after 24 h. We found that SDF-1 facilitated the migration potency of MSC both in vitro and in vivo, and this migration could be inhibited by AMD3100, an antagonist of CXCR4, and promoted by local infusion of exogenous SDF-1 into the distraction gap. This study provides a new insight into the molecular basis of how new bone is regenerated during distraction osteogenesis.

A comparison of stromal cell-derived factor-1 expression during distraction osteogenesis and bone fracture in the mandible.

Distraction osteogenesis (DO) has been a widely applied technique in orthopedics and craniofacial surgery. However, the exact molecular mechanism by which the mechanical stimulus is translated into biological signals is still poorly understood. In this study, we examined and compared the expression of stromal cell-derived factor-1 (SDF-1) during mandibular distraction osteogenesis and fracture in rats, respectively. Forty-eight male Sprague-Dawley rats were divided into 2 groups and received unilateral distraction osteogenesis and rigid internal fixation, respectively, after the osteotomy on the right mandible. The harvested mandibles were examined radiographically, histologically, and immunohistochemically. We found that the expression of SDF-1 was mainly detected in the osteoblasts and blood vessels, and there were more intensive expression of SDF-1 in DO zones than in bone fracture zones. The quantitative analysis by enzyme-linked immunosorbent assay showed that SDF-1 reached a greater peak and maintained a longer period of up-regulation in DO than in fracture healing (P < 0.05). These results suggest that the distraction procedure markedly promotes the high expression of SDF-1 which facilitates the induction of bone formation during DO.